Injection device with cammed ram assembly

Information

  • Patent Grant
  • 10905827
  • Patent Number
    10,905,827
  • Date Filed
    Wednesday, May 18, 2016
    8 years ago
  • Date Issued
    Tuesday, February 2, 2021
    3 years ago
Abstract
An exemplary embodiment of injector includes a trigger mechanism, an energy source, and a user-operable firing-initiation member. The trigger member can include a trigger member having a retainer portion, and a ram assembly having a ram configured to pressurize a medicament container for expelling a medicament therefrom and a trigger engagement member configured to engage the retainer portion of the trigger member in a pre-firing condition. The energy source can be associated with the ram for powering the ram to expel the medicament, and the user-operable firing-initiation member can be operable for causing an axial rotation between the trigger engagement member and the retainer portion from the pre-firing condition to a firing condition in which the trigger engagement member is released from the retainer portion to allow the energy source to fire the ram.
Description
FIELD OF THE DISCLOSURE

The present disclosure relates to injection devices, and in particular to a needle assisted jet injector.


BACKGROUND INFORMATION

Various injection devices exist that employ an automated mechanism to actuate injection of a liquid medicament into a patient. Examples of such devices include jet injectors (both needle-free and needle-assisted) and traditional, low-pressure auto-injectors (that provide, for example, mechanized delivery of a traditional, finger-powered hypodermic syringe injection). Although the precise mechanisms used to complete an injection can vary, most include a feature that stores kinetic energy that can be used to drive an injection mechanism during use. Further, many injectors include a trigger mechanism configured to ensure that the kinetic energy remains stored until an injection is desired, whereby actuation of the trigger releases the injection mechanism, allowing the stored kinetic energy to drive the injection mechanism to cause injection.


Examples of needle-free jet injectors are described, for example, in U.S. Pat. Nos. 5,599,302; 5,062,830; and 4,790,824. These injectors administer medication as a fine, high velocity jet delivered under sufficient pressure to enable the jet to pass through the skin. The injection mechanism in such needle-free jet injectors can apply a force to a medicament storing chamber within the device such that the pressure required to inject the medicament is created within the chamber.


Traditional self-injectors or auto-injectors like the ones described, for example, in U.S. Pat. Nos. 4,553,962 and 4,378,015 and PCT Publications WO/9929720 and WO/9714455 inject medicament at a rate and in a manner similar to hand-operated hypodermic syringes. The described self-injectors or auto-injectors have needles that are extended at the time of activation to penetrate the user's skin to deliver medicament through movement of the drug container and related needle. Thus, the mechanism that provides the force to deliver the medicament in traditional, low-pressure self-injectors and auto-injectors can also be used to extend the needle and displace the drug container to cause the insertion of the needle through the user's skin and to apply a force to a plunger movably disposed within the drug container to cause the medicament to be expelled from the container through the needle. The auto-injectors manufactured, for example by Owen Mumford, thus use very low pressures to inject the medicament, which is typically injected through a needle in a relatively slow stream. Another self-injector includes the Simponi injector, which includes a window in the housing through which a yellow ram is visible inside a clear medicament container once the injector has been used.


Additionally, needle-assisted jet injectors have also been developed that utilize a needle to initially penetrate the skin, to the higher injection forces allowing but not restricted to an insertion depth less than that of a traditional hypodermic injector or low-pressure auto-injectors. Once the skin is penetrated with the needle, a jet mechanism is activated, causing the medicament containing liquid within the injector to be pressurized and expelled through the needle and into the skin. The injection mechanism in needle-assisted jet injectors can be configured to move the drug container and the needle forward to penetrate the skin and exert the necessary injection force to a plunger moveably disposed within the container. Alternatively, the needle and drug container can be positioned to penetrate the skin while keeping the needle and drug container in a stationary position, and the injection mechanism can be structured to pressurize the container. The pressure applied to the medicament within the injector can be less than that of a traditional jet injector, because the outer layers of the skin have already been penetrated by the needle. Similarly, the pressure applied to the medicament is preferably higher than that of a traditional auto-injector or the like, causing the medicament to penetrate the skin or the tissue below the skin to a depth that is sufficient so that the medicament remains substantially within the body. An additional benefit of the higher pressure includes a faster time of injection resulting in less psychological trauma to the patient and a decreased likelihood of the user inadvertently terminating the injection prematurely by removing the injector from the injection site.


Because of the stored energy associated with the trigger and injection mechanisms, accidental firing can occur due to sudden movements during shipping or due to mishandling of the device by a user including accidental actuation of the trigger mechanism. Accidental firing of the injection mechanism can cause the medicament to be expelled from the device, which can be at a dangerously high pressure, depending on the type of injection device. Further, accidental firing can cause an injection needle to move forward with respect to the device with sufficient force to penetrate the skin.


Additionally, the dimensions of many components incorporated in injectors typically constrain the design of many injectors. For example, many injectors utilize front triggering mechanisms that typically require an axial translation and engagement with a triggering structure located at the back of the injector. However, this configuration typically prevents binding of the communicating triggering components, which can be advantageous for, e.g., reducing the size of the injection device, being able to view the drug container within the device, etc.


SUMMARY

Exemplary embodiments of the present disclosure are directed to injection devices. An exemplary embodiment of the present disclosure can provide an injector including a trigger mechanism, an energy source, and a user-operable firing-initiation member. The trigger member can include a trigger member having a retainer portion, and a ram assembly having a ram configured to pressurize a medicament container for expelling a medicament therefrom and a trigger engagement member configured to engage the retainer portion of the trigger member in a pre-firing condition. The energy source can be associated with the ram for powering the ram to expel the medicament, and the user-operable firing-initiation member can be operable for causing an axial rotation between the trigger engagement member and the retainer portion from the pre-firing condition to a firing condition in which the trigger engagement member is released from the retainer portion to allow the energy source to fire the ram. The exemplary injector can further include an injection housing, where the trigger engagement member and the ram are in fixed association, such that rotation of the trigger engagement member rotates the ram, and the ram assembly is associated with the firing-initiation member such that operation of the firing-initiation member rotates the ram assembly within the housing to the firing condition.


The exemplary injector can further include an injector housing. The firing initiation member can also include a skin-contacting member disposed at a distal end of the injector that is movable proximally with respect to the housing when a force is applied to the skin-contacting member at the distal end of the injector. Further, the firing initiation member can be associated with the trigger mechanism and configured to cause the axial rotation between the trigger engagement member and the retainer portion from the pre-firing condition to the firing condition upon a proximal movement of the skin-contacting member with respect to housing. Additionally, the skin-contacting member can include a needle guard that is retractable and is configured to expose a needle connected to the medicament container upon the proximal movement of the skin-contacting member.


According to another exemplary embodiment of the present disclosure, the needle can be in fluid communication with the medicament container for injecting the medicament expelled therefrom during the firing. Further, the energy source and the needle can be configured for jet injecting the medicament through the needle. The energy source can be configured to pressurize the medicament to between about 90 p.s.i. and about 500 p.s.i. to jet inject the medicament, and the energy source and needle can be configured for injecting the medicament at an average velocity of at least about 1,000 cm/sec within the needle.


According to another exemplary embodiment of the present disclosure, the skin contacting member can include a first cam, and the ram assembly can include a second cam. The first cam can be operatively associated with the second cam for camming the second cam upon the axial movement to rotate the ram assembly with respect to the retainer portion so as to position the ram assembly in the firing condition. The trigger mechanism can include a ram holding member that axially retains the ram assembly in a proximal position against action of the energy source in the pre-firing position, the retainer portion retaining the trigger engagement member engaged and held against firing by the ram holding member. Additionally, in the firing condition, the ram can be disengaged from the retainer portion, and the energy source overcomes an engagement between the trigger engagement member and the ram holding member. Further, the ram holding member can include a projection that includes a bulge and a groove engaged with the trigger engagement member, and the retainer portion retaining said engagement of the trigger engagement member with the bulge and groove, in the pre-firing condition.


According to certain exemplary embodiments of the present disclosure, the ram assembly can be of unitary construction.


According to yet another exemplary embodiment of the present disclosure, the injector can further include a container support that is configured for holding the medicament container during injection, and wherein the ram assembly is configured to engage the container support to lock-out the injector after an injection. Further, proximal movement of the user-operable firing-initiation member can be blocked by the ram assembly when the injector is locked-out.


According to yet another exemplary embodiment of the present disclosure, a pre-firing color gamut is visible from the exterior of the injector in the pre-firing condition. Further, the injector can further include a housing including a window; and an indicator having an indicator color that is absent from the pre-firing color gamut, which color is hidden from view within the housing in the pre-fired condition, and in the fired condition, the indicator color is visible through the window from the exterior of the injector for indicating the fired condition. In certain embodiments, the ram assembly can include the indicator, and the ram assembly can entirely occlude the window in the fired condition.


Yet another exemplary embodiment of the present disclosure can provide an injector including a trigger mechanism having a trigger member having a retainer portion, and a ram assembly having a ram configured to pressurize a medicament container for expelling a medicament therefrom and at least one first camming surface. The ram assembly can further include a trigger engagement member configured to engage the retainer portion of the trigger member in a pre-firing condition. The injector can further include an energy source associated with the ram for powering the ram to expel the medicament, and a needle guard including a user-operable firing-initiation member operable having at least one second camming surface configured to operatively associate with the at least one first camming surface so as to cause an axial rotation between the trigger engagement member and the retainer portion from the pre-firing condition to a firing condition in which the trigger engagement member is released from the retainer portion to allow the energy source to fire the ram. The injector can further include a container support, and the ram assembly can be configured to engage the container support to lock-out the injector after an injection.





BRIEF DESCRIPTION OF THE DRAWINGS

These and other objects, features and advantages of the invention will be apparent from a consideration of the following non-limiting detailed description considered in conjunction with the drawing figures, in which:



FIG. 1A is a side partial cross-sectional view of an exemplary injection device according to an exemplary embodiment of the present disclosure;



FIG. 1B is a cross-sectional view of an exemplary injection device according to an exemplary embodiment of the present disclosure;



FIG. 1C is a side view of a housing of an exemplary injection device according to an exemplary embodiment of the present disclosure;



FIG. 2A is a perspective view of a proximal portion of an exemplary injection device according to an exemplary embodiment of the present disclosure;



FIG. 2B is another perspective view of a proximal portion of an exemplary injection device according to an exemplary embodiment of the present disclosure;



FIG. 3 is a side view of an end housing portion of an exemplary injection device according to an exemplary embodiment of the present disclosure;



FIGS. 4A and 4B are side and perspective views respectively of a front housing portion and a sleeve of an exemplary injection device according to an exemplary embodiment of the present disclosure;



FIGS. 5A and 5B are side and perspective views respectively of a needle guard of an exemplary injection device according to an exemplary embodiment of the present disclosure;



FIGS. 6A and 6B are side and perspective views respectively of a ram assembly of an exemplary injection device according to an exemplary embodiment of the present disclosure;



FIG. 7 is an exploded view of an exemplary injection device according to an exemplary embodiment of the present disclosure;



FIGS. 8A-13C are side, cross-sectional, and internal views of an operation of an exemplary injection device according to an exemplary embodiment of the present disclosure;



FIG. 14 shows a cross sectional view of a cap of an exemplary injection device according to an exemplary embodiment of the present disclosure;



FIG. 15 shows a close-up view of an engagement of a trigger engagement member and a ram retaining member of an exemplary injection device according to an exemplary embodiment of the present disclosure;



FIG. 16 shows a side view of an exemplary injection device according to an exemplary embodiment of the present disclosure;



FIG. 17 shows a top view of a ram assembly of an exemplary injection device according to an exemplary embodiment of the present disclosure; and



FIG. 18 shows a partially cut-away perspective view of a proximal portion of an exemplary injection device according to another embodiment of the present disclosure.





Throughout the drawings, the same reference numerals and characters, unless otherwise stated, are used to denote like features, elements, components, or portions of the illustrated embodiments. Moreover, while the present disclosure will now be described in detail with reference to the figures, it is done so in connection with the illustrative embodiments and is not limited by the particular embodiments illustrated in the figures.


DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS


FIG. 1A shows an exemplary injection device 100 according to an exemplary embodiment of the present disclosure. It is noted that, in the context of this disclosure, the terms “distal” and “proximal” are used in reference to the position of the injection device relative to a user of the injection device when merely held by a user. Accordingly, a point located distal to a second point would be further from the user (i.e., towards an injection end of the injection device) and vice versa. As shown in the drawings, the exemplary injection device 100 is preferably a needle assisted jet injection device, although a person having ordinary skill in the art will understand alternative embodiments employing certain features herein can be configured as needle-free jet injectors, or as low-pressure auto-injectors or other mechanized injectors. According to certain exemplary embodiments, injection device 100 can be a one-time disposable needle-assisted jet injector with a lock-out feature. For example, injection device 100 can facilitate a jet injection of medicament stored within injection device 100 and can include a locking feature that prevents a user from attempting to use injection device 100 once the medicament has been dispensed. Preferably, the locking feature is activated upon dispensing of the medicament and not upon use of injection device 100. For example, the locking feature can be activated, thus preventing injection device 100 from a subsequent attempted use by a user, even in the case where the injection device was not used by a user for an injection, but where a firing mechanism was inadvertently activated (e.g., during transport, handling, etc. of the device) and the medicament was dispensed. Operation of injection device 100, including the locking feature, is described in further detail below.


According to certain exemplary embodiments, injection device 100 can deliver any suitable liquid drug or medicament. Further, injection device 100 can allow the injection to be administered by individuals that do not have formal training (e.g., self-administered or administered by another individual family member or other caregiver who may not be a formally trained healthcare provider, such as a parent administering a drug to a child). Accordingly, injection device 100 can be useful in situations where self-injections/caregiver administered injections would be beneficial, including, but not limited to, low T, hypogonadism, diabetes, infertility treatment, sexual dysfunction, cardiovascular disease, oncology supportive care, allergic reaction, multiple sclerosis, rheumatoid arthritis psoriasis, other autoimmune conditions including Crohn's disease and SLE, chronic pain, migraine, epileptic seizure, kidney disease, and the like. Further, injection device 100 can be used to inject a wide range of drugs. For example, injection device 100 can be used to inject drugs, water soluble medicaments and oil soluble medicaments. In one embodiment, the medicament includes a benzodiazepine, including midazolam. In another embodiment, the medicament is dissolved in oil instead of aqueous solutions, and can include hormone drugs used in men (e.g., testosterone, or a derivative or ester thereof) and women; small molecule injectable drugs such as, methotrexate (see, e.g., International Publication No. WO 2010/108116, which is incorporated by reference herein in its entirety); and/or biological drugs, including those having a high viscosity. Further, and as noted above, injection device 100 can be used to inject androgens, including testosterone formulations (e.g., testosterone cypionate and testosterone enanthate).


Testosterone is a steroid hormone from the androgen group. In general, androgens promote protein synthesis and growth of those tissues with androgen receptors. Testosterone is anabolic, meaning it builds up bone and muscle mass. Testosterone has the following structural formula:




embedded image


The original and primary use of testosterone is for the treatment of males who have too little or no natural endogenous testosterone production—males with Low T or hypogonadism. According to the Massachusetts Male Aging Study, about 6% to 12% men aged 40 to 60 years have symptomatic low testosterone deficiency. However, over the years, testosterone has also been given for many other conditions, e.g., reducing infertility, correcting lack of libido or erectile dysfunction, correcting osteoporosis, encouraging penile enlargement, encouraging height growth, encouraging bone marrow stimulation, reversing the effects of anemia and appetite stimulation.


In certain embodiments, injection device 100 can be used to inject one or more of epinephrine, atropine, dihydroergotamine, sumatriptan, antibiotics, antidepressants, anticoagulants, glucagon, diazepam, haloperidol, apomorphine, lovenox, and toradol. In other embodiments, injection device 100 can be used to inject biosimilar, biological and or peptide drugs, including without limitation Enbrel, Humira, Lantus, Epogen (Procrit), Neulasta, Aranesp, Avonex, PEGasys, Rebif, Neupogen, Betaseron, Avastin, Remicade, Herceptin, Erbitux, Recombinate, Cerezyme, NovoSeven, Tysabri, Synagis, Copaxone and Kogenate FS.


In other embodiments, injection device 100 can be used to inject parathyroid hormone (“PTH”) and various other medications such as exenatide and the like. Injection device 100 can also be used to inject medicaments listed in the Physicians' Desk Reference (PDR®), 67th Edition (2013) (which is herein incorporated by reference in its entirety), and, without limitation, allergens, amebicides and trichomonacides, amino acid preparations, analeptic agents, analgesics, analgesics/antacids, anesthetics, anorexics, antacids, antihelmintics, antialcohol preparations, antiarthritics, antiasthma agents, antibacterials and antiseptics, antiviral antibiotics, anticancer preparations, anticholinergic drug inhibitors, anticoagulants, anticonvulsants, antidiabetic agents, antidiarrheals, antidiuretics, antienuresis agents, antifibrinolytic agents, antifibrotics (systemic), antiflatulents, antifungal agents, antigonadotropin, antihistamines, antihyperammonia agents, anti-inflammatory agents, antimalarials, antimetabolites, antimigraine preparations, antinauseants, antineoplastics, anti-obesity preparations, antiparasitics, anti-parkinsonism drugs, antipruritics, antipyretics, antispasmodics and antichloinergics, antitoxoplasmosis agents, antitussives, antivertigo agents, antiviral agents, biologicals, biosimilars, bismuth preparations, bone metabolism regulators, bowel evacuants, bronchial dilators, calcium preparations, cardiovascular preparations, central nervous system stimulants, cerumenolytics, chelating agents, choleretics, cholesterol reducers and anti-hyperlipemics, colonic content acidifiers, cough and cold preparations, decongestants, diazepam, epinephrine expectorants and combinations, diuretics, emetics, enzymes and digestants, fertility agents, fluorine preparations, galactokinetic agents, general anesthetic, geriatrics, germicides, hematinics, hemorrhoidal preparations, histamine H receptor antagonists, hormones, hydrocholeretics, hyperglycemic agents, hypnotics, immunosuppressives, laxatives, mucolytics, muscle relaxants, narcotic antagonists, narcotic detoxification agents, ophthalmological osmotic dehydrating agents, otic preparations, oxytocics, parashypatholytics, parathyroid preparations, pediculicides, phosphorus preparations, premenstrual therapeutics, psychostimulants, quinidines, radiopharmaceuticals, respiratory stimulants, salt substitutes, scabicides, sclerosing agents, sedatives, sympatholytics, sympathomimetics, thrombolytics, thyroid preparations, tranquilizers, tuberculosis preparations, uricosuric agents, urinary acidifiers, urinary alkalinizing agents, urinary tract analgesic, urological irrigants, uterine contractants, vaginal therapeutics and vitamins and each specific compound or composition listed under each of the foregoing categories in the PDR®. Some other medicaments that can be used with injector device 100 include Ergocalciferol (Calciferol), diethylstilbestrol, Diprovan (propofol), estradiol valerate, fluphenazine decanoate, fulvestrant, intralipid, liposyn, nandrolone decanoate, nebido, nutralipid, paclitaxel, progesterone, prograf, testosterone cypionate, zuclopenthixol, and haloperidol dodecanoate. In certain embodiments, the medicament is dissolved in soybean oil, ethyl oleate, castor oil, sesame oil, safflower oil, arachis oil, polyoxyethylated castor oil (Cremophor® EL), polyoxyl 60 hydrogenated castor oil (HCO-60), cottonseed oil, or thin oil derived from coconut oil.


In some embodiments, the medicament may be a hazardous agent. “Hazardous Agent(s)” as used herein means any one or more medications that are toxic agents, cytotoxic agents and/or other dangerous agents that may cause serious effects upon contact with a subject as well as highly potent agents, agents that have profound physiological effects at low doses. Exemplary hazardous agents include, without limitation, analgesics, immunomodulating agents, IL-1 receptor antagonists, IL-2 alpha receptor antagonists, anti-rejection compounds, hormonal agents, prostaglandins, sedatives, anticholinergic agents, Parkinsons disease drugs, expensive agents, neuroleptic agents, tissue necrosis factor (TNF) blockers, and other dangerous agents. Examples of hazardous agents suitable for use with injection device 100 in accordance with the present invention include, but are not limited to, those disclosed in U.S. Patent Application Publication No. 2012/0157965 entitled “Hazardous Agent Injection System” (to Paul Wotton et. al, published Jun. 21, 2012), which is incorporated by reference herein in its entirety. Particular examples of cytotoxic agents include, without limitation, 6-mercaptopurine, 6-thioinosinic acid, azathioprine, chlorambucil, cyclophosphamide, cytophosphane, cytarabine, fluorouracil, melphalan, methotrexate, uramustine, anti-cytokine biologicals, cell receptor antagonists, cell receptor analogues, and derivatives thereof. Examples of highly potent agents include, without limitation, steroids such as dexamethasone, progesterone, somatostatin, and analogues thereof; biologically active peptides such as teriparatide; and anticholinergics such as scopolamine. Examples of agents that have profound physiological effects at low doses include, without limitation, antihypertensives and/or blood pressure down regulators. Examples of analgesics include, without limitation, fentanyl, fentanyl citrate, morphine, meperidine, and other opioids. Examples of immunomodulating agents include, without limitation, adalimumab (anti-tissue necrosis factor monoclonal antibody or anti-TNF). Examples of IL-1 receptor antagonists include, without limitation, anakinra. Examples of IL-2 alpha receptor antagonists include, without limitation, daclizumab and basiliximab. Examples of anti-rejection compounds include, without limitation, azathioprine, cyclosporine, and tacrolimus. Examples of hormonal agents include, without limitation, testosterone, estrogen, growth hormone, insulin, thyroid hormone, follicle stimulating hormone (FSH), epinephrine/adrenaline, progesterone, parathyroid hormone, gonadotrophin releasing hormone (GHRH), leutinizing hormone releasing hormone (LHRH), other hormones such as those where contact with the hormone by members of the opposite sex can lead to side effects, and derivatives thereof. Examples of prostaglandins include, without limitation, gamma-linolenic acid, docosahexanoic acid, arachidonic acid and eicosapentaenoic acid. Examples of sedatives include, without limitation, barbiturates such as amobarbital, pentobarbital, secobarbital, and phenobarbitol; benzodiazepines such as clonazepam, diazepam, estazolam, flunitrazepam, lorazepam, midazolam, nitrazepam, oxazepam, triazolam, temazepam, chlordiazepoxide, and alprazolam; herbal sedatives such as ashwagandha, duboisia hopwoodii, prosanthera striatiflora, kava (piper methysticum), mandrake, valerian, and marijuana, non-benzodiazepine sedatives (a.k.a. “Z-drugs”) such as eszopiclone, zaleplon, zolpidem, zopiclone; antihistamines such as diphenhydramine, dimenhydrinate, doxylamine, and promethazine; and other sedatives such as chloral hydrate. Examples of anticholinergic agents include, without limitation, dicyclomine, atropine, ipratropium bromide, oxitropium bromide, and tiotropium. Examples of Parkinson's disease drugs include, without limitation, levodopa, dopamine, carbidopa, benserazide, co-ceraldopa, co-beneldopa, tolcapone, entacapone, bromocriptine, pergolide, pramipexole, ropinirole, piribedil, cabergoline, apomorphine, and lisuride. Examples of expensive agents include, without limitation, human growth hormone and erythropoietin. Examples of neuroleptic agents includes, without limitation, antipsychotics; butyrophenones such as haloperidol and droperidol; phenothiazines such as chlorpromazine, fluphenazine, perphenazine, prochlorperazine, thioridazine, trifluoperazine, mesoridazine, periciazine, promazine, triflupromazine, levomepromazine, promethazine, and pimozide; thioxanthenes such as chlorprothixene, clopenthixol, flupenthixol, thiothixene, and zuclopenthixol; atypical antipsychotics such as clozapine, olanzapine, risperidone, quetiapine, ziprasidone, amisulpride, asenapine, paliperidone, iloperidone, zotepine, and sertindole; and third generation antipsychotics such as aripiprazole and bifeprunox. Examples of TNF blockers includes, without limitation, etanercept.


In some embodiments, the hazardous agent can be selected from botulinum toxin, injectable gold, 6-mercaptopurine, 6-thioinosinic acid, azathioprine, chlorambucil, cyclophosphamide, cytophosphane, cytarabine, fluorouracil, melphalan, methotrexate, uramustine, anti-cytokine biologicals, cell receptor antagonists, cell receptor analogues, dexamethasone, progesterone, somatostatin, analogues of dexamethasone, analogues of progesterone, analogues of somatostatin, teriparatide, scopolamine, antihypertensives, blood pressure down regulators, fentanyl, fentanyl citrate, morphine, meperidine, other opioids, adalimumab (anti-tissue necrosis factor monoclonal antibody or anti-TNF), anakinra, daclizumab, basiliximab, azathioprine, cyclosporine, tacrolimus, testosterone, estrogen, growth hormone, insulin, thyroid hormone, follicle stimulating hormone (FSH), epinephrine/adrenaline, gamma-linolenic acid, docosahexanoic acid, arachidonic acid, eicosapentaenoic acid, amobarbital, pentobarbital, secobarbital, phenobarbitol, clonazepam, diazepam, estazolam, flunitrazepam, lorazepam, midazolam, nitrazepam, oxazepam, triazolam, temazepam, chlordiazepoxide, alprazolam, ashwagandha, duboisia hopwoodii, prosanthera striatiflora, kava (piper methysticum), mandrake, valerian, marijuana, eszopiclone, zaleplon, zolpidem, zopiclone, diphenhydramine, dimenhydrinate, doxylamine, promethazine, chloral hydrate, dicyclomine, atropine, ipratropium bromide, oxitropium bromide, tiotropium, levodopa, dopamine, carbidopa, benserazide, co-ceraldopa, co-beneldopa, tolcapone, entacapone, bromocriptine, pergolide, pramipexole, ropinirole, piribedil, cabergoline, apomorphine, lisuride, human growth hormone, erythropoietin, haloperidol, droperidol, chlorpromazine, fluphenazine, perphenazine, prochlorperazine, thioridazine, trifluoperazine, mesoridazine, periciazine, promazine, triflupromazine, levomepromazine, promethazine, pimozide, chlorprothixene, clopenthixol, flupenthixol, thiothixene, zuclopenthixol, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, amisulpride, asenapine, paliperidone, iloperidone, zotepine, sertindole, aripiprazole, bifeprunox, etanercept, derivatives of any of the foregoing, and combinations of any of the foregoing.


While injection device 100 can deliver an injection of up to approximately 1 mL per injection, other volumes can be injected in alternative embodiments.


According to certain exemplary embodiments, injection device 100 can be configured to inject medicament stored within a prefilled syringe. Prefilled syringes that are manufactured by a blown glass process can have significant dimensional tolerances and unevenness. Accordingly, features of injection device 100 can serve to accommodate the shape irregularities and to properly position and locate a prefilled syringe within injection device 100. Further, injection device 100 can be configured as a needle-assisted jet injector, providing a peak pressure during the injection of less than about 1,000 p.s.i., preferably less than 500 p.s.i., and more preferably less than about 350 p.s.i. At an end of an injection, the pressure applied to the medicament is preferably at least about 80 p.s.i., more preferably at least about 90 p.s.i., and most preferably at least about 100 p.s.i. In one embodiment, the initial pressure can be around 330 p.s.i., and the final pressure can be about 180 p.s.i., while in another embodiment the initial pressure can be about 300 p.s.i., dropping to around 110 p.s.i. at the end of the injection. These exemplary pressures can, for example, result in a flow rate of about 0.2 mL/sec to 0.75 mL/sec, and preferably about 0.5 mL/sec. The needles used are preferably between 26 and 28 gauge, and are most preferably around 27 gauge, but alternatively other needle gauges can be used where the other components are cooperatively configured to produce the desired injection. In preferred jet injector embodiments firing aqueous medicaments, the firing mechanism, medicament container, needle, and energy source are configured to produce an average stream velocity within the needle of at least about 1,000 cm/sec, and more preferably at least about 1,500 cm/sec, up to about 5,000 cm/sec, and more preferable up to about 3,000 cm/sec. In one embodiment, the average stream velocity during injection is about or reaches between about 1,800 and 2,200 cm/sec or approximately 2,000 cm/sec. The velocities used to produce a jet injection will vary for other types of medicaments, such as based on their viscosities. Weaker energy sources, and/or larger needles, for example, can be used to obtain lower velocities and lower pressures and/or flow rates for traditional, low-pressure autoinjector embodiments. Such embodiments can also benefit from the axial rotation between the trigger engagement member and the retainer portion, while moving from the pre-firing condition to the firing condition upon a proximal movement of the skin-contacting member with respect to housing.


As shown in FIG. 1B, the exemplary injection device 100 can include an outer housing 102, a cap 104, and a housing end/end cap 106. Injection device 100 can further include various components and/or assemblies housed within outer housing 102. As shown in FIG. 1B, these components can include a guard 108, a container support, such as, e.g., a sleeve 110, a firing mechanism 112, a medicament chamber 114, a needle 116, and a spring 118. As shown in FIG. 1A, outer housing 102 can be a single piece component, or alternatively, outer housing 102 multiple piece assembly that can be coupled together, for example, via a snap-fit connection, a press-fit connection, a threaded engagement, adhesives, welding, or the like.


As shown in FIG. 1B, cap 104 is removably affixable to a distal end of outer housing 102, and housing end/end cap 106 is coupled to a proximal end of housing 102. For example, cap 104 can be removably affixed to the distal end of housing 102 via a threaded engagement and housing end 106 can include features (e.g., projections) configured to engage a portion of the proximal end of housing 102 (e.g., openings) to couple housing end/end cap 106 to housing 102. When affixed to injection device 100, cap 104 can ensure that an injection is not triggered by an inadvertent application of a force to guard 108. Preferably, cap 104 includes two engagement features. As shown in FIG. 14, cap 104 can include engagement features 1040 and 1042. Engagement features 1040 and 1042 can be threads configured to threadedly engage other features of injection device 100. For example, engagement feature 1040 can be configured secure cap 104 to the distal end of housing 102 (e.g., via a threaded engagement with a distal portion of sleeve 110), and engagement feature 1042 can be configured to threadedly engage features of guard 108 to prevent proximal displacement of guard 108. For example, FIG. 1B shows feature 1042 engaged with feature 1080a of guard 108, thereby preventing proximal movement of guard 108, such as may occur if the injector is accidentally dropped or otherwise jolted.


Additionally, cap 104 is preferably non-circular in cross-section viewed along its axis and in the initial, closed position aligns with or substantially matches the shape of the portion of the housing adjacent thereto. Features 1040 can include a plurality of threads, having more than one thread starting point, only one of which will result in the cap lining up with the housing as in the initial closed position. Consequently, if the cap is removed and replaced, there is a chance that an incorrect starting point will be selected by the user, resulting in the cap no longer aligning with the injector housing, and providing an indication of tampering. In one embodiment, three threads are used, so there is a two in three chance that a removed and replaced cap will become immediately obvious based on an ill-fitting cap.


As shown in FIG. 1C, housing 102 can include openings 1024 configured to engage with sleeve 110 to couple and secure sleeve 110 to housing 102 and can include at least one window 1020 that can provide a visual indication of whether or not injection device 100 has been fired. For example, in an unfired state, window 1020 can allow a user to see medicament chamber 114, along with the stored medicament, and in a fired state, window 1020 can show one or more internal components, such as a portion of firing mechanism 112, which can be a color specifically selected to alert the user that injection device 100 has been fired, and is preferably sufficiently different than other colors visible to a user (preferably having ordinary eyesight) on the injector prior to firing, so as to be conspicuously different to, or contrast from, any other colors present or significantly present. For example, the color can differ from all the other components of injection device 100 pre-firing, or visible by the user pre-firing, so as to be conspicuous (e.g., introducing an entirely new color family). The new color appearing after firing, can be from a non-analogous part of the color wheel, or can contrast, or can be a complementary color, with respect to the colors visible on injection device 100. The new color can signify caution, such as red or orange, etc. In one embodiment, the colors visible on the injector in the pre-firing condition, preferably including when the cap 104 is on and/or off the injector, are grays and blues, for instance. When the injector is fired, the color red can be introduced. Preferably, this new color can be introduced after firing but prior to guard 108 being locked-out in the extended position.


A proximal end of housing 102 can also include a trigger member, which can include a trigger member retaining portion 1022. For example, trigger member retaining portion 1022 can include an opening configured to receive and engage at least a trigger engagement member of firing mechanism 112 (e.g., projections) in facilitating firing of injection device 100. Opening 1022 is preferably configured to engage a trigger engagement member, e.g., projections 1134 of firing mechanism 112, for example latch tabs, such that they are aligned in one of two positions. For example, in first position 1022a (e.g., retaining position), the opening can include retaining portions so that projections 1134 of firing mechanism 112 are aligned so that they can be restrained by lateral sides of opening 1022, thereby preventing firing mechanism 112 from firing (e.g., by preventing projections 1134 from splaying open firing mechanism 112 is prevented from slidably displacing under a force exerted by an energy source) and dispensing the medicament. In second position 1022b (e.g., firing position), the opening can include firing portions such that the projections of firing mechanism 112 are aligned such that projections can splay apart, thereby permitting firing mechanism 112 to fire. FIG. 2A shows projections 1134 aligned in the first position (1022a) and FIG. 2B shows projections 1134 aligned in the second position (1022b). Further, the lateral walls of the retaining portions of the opening (e.g., in the first position 1022a) are preferably curved to facilitate rotation of projections 1134 between the first and second positions.


Injection device 100 also preferably includes housing end/end cap 106. As shown in FIG. 3, housing end/end cap 106 preferably includes a body portion 1060 and a ram holding member 1062. Ram holding member 1062 can be a projection, and can be configured to engage a trigger engagement member of firing mechanism 112. For example, ram holding member 1062 can be a bell-shaped projection, and can engage a complementary shaped feature (e.g., projections) of firing mechanism 112. In an exemplary embodiment, ram holding member 1062 can include a groove 1062a and a bulge 1062b, and features of firing mechanism 112 can be configured to align with groove 1062a so as to hold bulge 1062b to prevent firing of injection device 100. Preferably, ram holding member 1062 and the features of firing mechanism 112 engaging with ram holding member 1062 include a circular cross section to allow rotation of the features of firing mechanism 112 relative to ram holding member 1062 during firing of injection device 100. Further, body portion 1060 can include projections 1060a configured to engage openings in outer housing 102 to couple housing end/end cap 106 to housing 102. In an exemplary embodiment.


As shown in FIG. 1B, sleeve 110 is preferably at least partially housed within outer housing 102 and mounted to outer housing 102 via, for example, a snap-fit connection, a press-fit connection, a threaded engagement, adhesives, welding, or the like. As shown in FIGS. 4A and 4B, for example, sleeve 110 can include projections 1108 configured to engage openings 1024 of housing 102. Sleeve 110 is configured to hold a medicament chamber 114, which can include a needle 116 at a distal end of medicament chamber 114. In certain exemplary embodiments, medicament chamber 114 can include, for example, a separate glass ampule and a needle, or a pre-filled syringe, or sleeve 110 itself can include an integral medicament chamber. Preferably, a plunger 1140 is provided in the medicament chamber 114. Plunger 1140 is in association with a ram 1132 of firing mechanism 112. During an injection, ram 1132 is urged by an energy source of firing mechanism 112 to displace plunger 1140 distal, deeper into medicament chamber 114, dispensing the medicament through needle 116. Needle 116 can include an injecting tip 1160 that can be configured to penetrate the skin of a user and a hollow bore that is in fluid communication with medicament chamber 114 to facilitate delivery of medicament from medicament chamber 114 to a user during an injection. FIGS. 1A and 1B show injection device 100 in a pre-firing state, with cap 104 secured to outer housing 102 and injection device 100 in a pre-firing position. The operation of injection device 100, including its various stages and positions, are described in further detail below.


As shown in FIGS. 4A and 4B, sleeve 110 can include a ring-like structure 1100, a coupling arrangement 1102, and a body portion 1104. Coupling arrangement 1102 can be disposed at a distal portion of sleeve 110 and can be configured to releasably engage cap 104. For example, coupling arrangement 1102 can include threads configured to provide threaded engagement between sleeve 110 and cap 104. Further, sleeve 110 can include a body portion 1104 configured to secure medicament chamber 114. Body portion 1104 can include guides, such as grooves 1104a, configured to engage with features of guard 108 to align and guide axial displacement of guard 108. A proximal end of sleeve 110 can include a medicament chamber support 1106 configured to support and secure a proximal portion of medicament chamber 114. For example, support 1106 can be configured as a syringe support configured to hold a proximal end of syringe (e.g., finger flanges of a prefilled syringe) and can support medicament chamber 114 during the forces exerted on it during firing. Further, support 1106 can include an elastomer or a rubber, and can be configured to at least partially absorb the shock or a force exerted on medicament chamber 114 during an injection. Additionally, sleeve 110 can include various features, such as projections 1108, configured to couple sleeve 110 to outer housing 102. For example, projections 1108 can to concentrically symmetrical and configured to engage openings 1024 in outer housing 102 to secure sleeve 110 to outer housing 102. In an exemplary embodiment, projections 1108 can be disposed on legs 1110, which can be concentrically symmetrical and configured to engage with features of guard 108. Additionally, sleeve 110 can include locking features, such as locking projections 1112, disposed on legs 1114, which can be concentrically symmetrical, and can be configured to engage firing mechanism 112 in locking out injection device 100 to prevent a user from attempting to use an already-fired injection device 100.


Ring-like structure 1100 can include several features configured to engage sleeve 110 with glass medicament chamber 114, firing mechanism 112, and guard 108. For example, ring-like structure 1100 can include an opening 1116 through which needle 116 can be received. Further, ring-like structure 1100 can include concentrically symmetrical openings 1118 which can be configured to receive legs of guard 108. Additionally, ring-like structure 1100 can be configured to support a distal portion of medicament chamber 114 and engage firing mechanism 112 in preventing further axial displacement of firing mechanism 112 during dispensing of the medicament. Operation of these components are described in further detail below.


As shown in FIGS. 5A and 5B, injection device 100 preferably includes a guard 108 slidably mounted at least partially within outer housing 102 and configured to engage firing mechanism 112 to actuate firing of injection device 100. Preferably, guard 108 is slidably movable relative to outer housing 102 between an extended (e.g., a distal, protective) position and a retracted (e.g., proximal) position. In the extended position, guard 108 preferably covers needle 116, and in the retracted position, needle 116 is not covered by guard 108 and is thereby exposed. For example, FIG. 9A shows guard 108 in the extended position, and FIG. 10A shows guard 108 in the retracted position. Preferably, guard 108 is resiliently biased toward the extended position via a spring 118, which can be disposed, for example, between a distal surface of ring-like structure 1100 of sleeve 110 and an interior surface of a distal end of guard 108.


In an exemplary embodiment, guard 108 includes a distal portion 1080 and legs 1082. In an exemplary embodiment, the distal end of guard 108 preferably includes a skin-contacting member. Distal portion 1080 includes an opening through which needle 116 can pass and projections 1080a. Projections 1080a can be configured to about a distal edge of sleeve 110 so as to limit the proximal displacement of guard 108. For example, as guard 108 is proximally displaced under a force applied by a user during an injection, projections 1080a will come into contact with the proximal edge of sleeve 110 so that guard 108 cannot be further proximally displaced. Further, projection 1080a can be configured to engage engagement feature 1042 of cap 104 so that guard 108 cannot be proximally displaced when engaged with engagement feature 1042 of cap 104.


Legs 1082 of guard 108 are preferably configured to be received in openings 1118 of ring-like structure 1100. Further, legs 1082 can include ridges 1082a configured to engage grooves 1104a of sleeve 110, to facilitate alignment and guiding of legs 1082 as guard 108 is axially displaced. As shown in the exemplary embodiments of FIGS. 5A and 5B, legs 1082 also preferably include firing-initiation members, such as camming surfaces 1084 at a proximal end of legs 1082. In an exemplary embodiment, legs 1082 and camming surface 1084 can be concentrically symmetrical. Camming surfaces 1084 are configured to engage firing mechanism 112 in initiating a firing of injection device 100 and performing an injection of the medicament stored in medicament chamber 114. The proximal ends of legs 1082 can also be sloped to facilitate legs 1082 being received within firing mechanism 112 when guard 108 is displaced from the extended position to the retracted position. Preferably, legs 1082 include projections 1086 disposed on springs 1088 which can also include sloped surfaces 1088a. Projections 1086 can be configured to engage proximal surfaces of legs 1110 of sleeve 110 to oppose a force exerted by spring 118, which biases guard 108 in the extended position. Further, sloped surfaces 1088a can be configured to engage an interior surface of legs 1110 of sleeve 110 so that as guard 108 is displaced from the extended position to the retracted position, sloped surfaces 1088a engage the interior surfaces of legs 1110 so as to bias springs 1088 towards an interior of injection device 100.


As shown in FIG. 1B, injection device 100 also preferably includes firing mechanism 112. Firing mechanism 112 can include a ram assembly 1120 slidably mounted within housing 102 and an energy source 1122. In an exemplary embodiment, the energy source 1122 preferably includes a compression spring 1122, however, other suitable energy source can be used, such as an elastomer or compressed-gas spring, or a gas generator, or other suitable energy storage members. In FIG. 1A, ram assembly 1120 is in a pre-firing proximal-most position. During an injection, ram assembly 1120 is urged distally by energy released by energy source 1122. Once an injection is completed, firing ram assembly 1120 is disposed in a distal position (as shown in FIG. 12B). In this distal position, guard 108 is locked-out so that a user cannot attempt a subsequent injection. Although shown as a single piece, ram assembly 1120 can be a multiple piece assembly that can be coupled together, for example, via a snap-fit connection, a press-fit connection, a threaded engagement, adhesives, welding, or other suitable couplings. Ram assembly 1120 preferable includes various features that can be configured to facilitate firing of injection device 100 to dispense the medicament stored in medicament chamber 114. According to certain exemplary embodiments of the present disclosure, a trigger mechanism of injection device 100 can include ram assembly 1120, the trigger member and trigger retaining portion 1022, and ram retaining holding member 1060.


As shown in FIGS. 6A and 6B, in an exemplary embodiment, ram assembly 1120 can include a distal portion 1124 and a proximal portion 1126 separated by a feature 1138, such as a lip, a ledge, that can be configured to act as a seat for energy source 1122. In an exemplary embodiment, compression spring 1122 can be disposed between a proximal end of housing 102 and feature 1138. Distal portion 1124 can be substantially cylindrical and can be configured to concentrically receive at least a portion of sleeve 110 and guard 108. Distal portion 1124 can also include openings 1128 configured to receive legs 1110 of sleeve 110 and projection 1086 of guard 108. An interior surface of distal portion 1124 can include camming surfaces 1124a configured to engage camming surfaces 1084 of guard 108. FIG. 16 shows engagement of camming surfaces 1124a with camming surfaces 1084 of guard 108 in a pre-fired state. As guard 108 is moved proximally during an injection, the axial movement of guard 108 is translated into a rotational movement of ram assembly 1120 via the engagement of camming surfaces 1124a and 1084.


Proximal portion 1126 preferably includes legs 1130, a ram 1132, and a trigger engagement member, such as, e.g., projections 1134. Although the trigger engagement member is shown as projections 1134, alternative implementations are contemplated. The trigger engagement member can include any feature (e.g., an elongated tab, a recess, a protrusion, a bulge, a thread, etc.) that can be held by ram retaining member in the pre-firing state, and released upon rotation of the trigger engagement member. For example, the ram retaining member can be shaped such that it prevents axial movement of the trigger engagement member in a first position, but releases trigger engagement member in a rotationally translated second position. Camming surfaces 1124a and 1084 are preferably oriented at an angle with respect to the longitudinal axis of the device to achieve a selected force and throw required to depress the guard 108 from the extended to the retracted position to fire the device. In some embodiments, the camming surfaces are angled at between 15° and 75° with respect to the axis, and more preferably between about 20° and 45°. In one embodiment, the camming surfaces are angles at about 30° with respect to the axis.


As shown in FIGS. 6A and 6B, legs 1130 include openings 1136 configured to engage locking projections 1112 of sleeve 110. For example, locking projections 1112 of sleeve 110 can engage openings 1136 of firing mechanism 112 after injection device 100 has been fired, locking-out injection device 100 so that a user cannot initiate another firing of injection device 100. Ram 1132 is configured to be in association with plunger 1140, and distally displace plunger 1140 under the force of energy source 1122 to dispense the medicament contained in medicament chamber 114 during an injection. Additionally, projections 1134 can be disposed at a proximal end of proximal portion 1126 and can be configured to engage opening 1022 of housing 102 and ram holding member 1062 of housing end/end cap 106. The engagement of projections 1134 with opening 1022 and ram holding member 1062, as well as the alignment of projections 1134 within opening 1022 can control and enable firing of injection device 100. For example, projections 1134 can include bulges 1134a configured to engage groove 1062a of ram holding member 1062, and shapes 1134b configured to engage bulge 1062b of ram holding member 1062. As noted above, projections 1134 and ram holding member 1062 preferably include circular cross-sections to allow rotation of ram assembly 1120 during firing of injection device 100. FIG. 15 shows a closeup view of the engagement of trigger engagement member (e.g., projections 1134) with ram holding member 1062.


In certain embodiments, the engagement of the ram holding member 1062 of housing end/end cap 106 with projections 1134 of ram assembly 1120 creates a latch retention angle 1500. In one embodiment, latch retention angle 1500 is defined by axis 1502 and the contact surface of a distal portion of groove 1062a of ram holding member 1062 of housing end/end cap 106 and bulge 1134a of projections 1134 of ram assembly 1120. In certain embodiments, projections 1134 and ram holding member 1062 are sized and shaped to create, when engaged, a latch retention angle 1502 of about 10°, about 11°, about 12°, about 13°, about 14°, about 15°, about 16°, about 17°, about 18°, about 19°, about 20°, about 21°, about 22°, about 23°, about 24°, about 25°, about 26°, about 27°, about 28°, about 29°, about 30°, about 31°, about 32°, about 33°, about 34°, about 35°, about 36°, about 37°, about 38°, about 39°, about 40°, about 41°, about 42°, about 43°, about 44°, about 45°, about 46°, about 47°, about 48°, about 49°, about 50°, about 510, about 52°, about 53°, about 54°, about 55°, about 56°, about 57°, about 58°, about 59°, about 60°, about 61°, about 62°, about 63°, about 64°, about 65°, about 66°, about 67°, about 68°, about 69°, about 70°, about 71°, about 72°, about 73°, about 74°, about 75°, about 76°, about 77°, about 78°, about 79°, about 80°, about 81°, about 82°, about 83°, about 84°, about 85°, about 86°, about 870, about 88°, about 89° or any range determinable from the preceding angles (for example, about 39° to about 41° or about 79° to about 81°).



FIGS. 8A-12B show the various stages and states of exemplary injection device 100. FIGS. 8A and 8B show injection device 100 in a pre-firing “safeties-on” configuration. For example, in the pre-firing “safeties-on” configuration, injection device 100 is in a pre-firing state and cap 104 is affixed to injection device 100. In this configuration, guard 108 is in the extended position under force of spring 118 covering needle 116, ram assembly 1120 is in its proximal position, and energy source 1122 has not released its energy. Further, in this state, projections 1134 of ram assembly 1120 are engaged with opening 1022 and aligned in the first position 1022a (e.g., pre-firing condition) of opening 1022. Further, projection 1134 are also engaged with ram holding member 1062 of housing end/end cap 106. In this position, the engagement of projections 1134 with ram holding member 1062 of housing end/end cap 106 oppose the force of energy source 1122. Further, with projections 1134 aligned within the first position 1022a of opening 1022, the lateral sides of opening 1022 (formed by the proximal end of housing 102) prevent projections 1134 from splaying open and disengaging ram holding member 1062 under the force of energy source 1122.


In FIGS. 9A and 9B, injection device 100 is shown in a pre-firing “ready-to-use” state. FIG. 13A shows many of the internal components of injection device 100 in this pre-firing “ready-to-use” state without showing housing 102. For example, safety member 104 has been removed, but the user has not otherwise initiated an injection. Accordingly, in this state, the medicament is still in medicament chamber 114, guard 108 remains in an extended position covering needle 116, energy source 1122 has not released the energy that its has stored, and projections 1134 of ram assembly 1120 remains engaged with ram holding member 1062 and aligned in the first position (1022a) of opening 1022.



FIGS. 10A and 10B show injection device 100 in a triggered or “just-used” state. FIG. 13B shows many of the internal components of injection device 100 in this triggered or “just-used” state without showing housing 102. In this state, guard 108 has been proximally slidably displaced (e.g., by application of a force on the distal end of guard 108) from the extended position to the retracted position, thereby exposing needle 116. Energy source 1122 is just beginning to release its stored energy (e.g., the exemplary compression spring remains compressed), and ram assembly 1120 remains in the proximal-most position. Injection device 100 may be in this state, for example, during an initial stage of use by a user. For example, this can be observed when the user has pressed guard 108 of injection device 100 against an injection site to perform an injection. Accordingly, the force exerted by the user in pressing guard 108 of injection device 100 against the injection site may have proximally displaced guard 108 against the force of spring 118, thereby displacing guard 108 into the retracted position and exposing needle 116 to penetrate the user's skin at the injection site.


In this triggered state shown in FIG. 10B, guard 108 has been displaced into the retracted position, camming surfaces 1084 of guard 108 engage camming surfaces 1024a disposed on the interior of ram assembly 1120, thereby camming ram assembly 1120 (see FIG. 16). This camming action rotates ram assembly 1120, causing projections 1134 to become unaligned with the first position of opening 1022 and become aligned with the second position of opening 1022. In this position, projections 1134 are no longer restrained from splaying open by the lateral walls of opening 1022. Accordingly, projections 1134 splay open under the force of, energy source 1122, causing projections 1134 to disengage with ram holding member 1062 of housing end/end cap 106. The disengagement of projections 1134 with ram holding member 1062 allows ram assembly 1120 to be distally slidably displaced relative to housing 102 under the force generated by energy source 1122. The distal displacement of ram assembly 1120 is preferably restrained by ram assembly 1120 abutting a proximal surface of ring-like structure 1100 of sleeve 110.



FIGS. 11A and 11B show injection device 100 in a “just-injected” state. This state follows the disengagement of projections 1134 with ram holding member 1062 and the distal displacement of ram assembly 1120 described above. In this state, energy source 1122 (e.g., a compression spring) has released its energy, thereby distally displacing ram assembly 1120. Further, guard 108 remains compressed in the retracted position. This state may be observed during use of injection device 100 immediately following the state shown in FIGS. 10A and 10B. As described above, camming of ram assembly 1120 aligns projections 1134 with the second position defined by opening 1022, allowing projections 1134 to splay open and disengage ram holding member 1062 under the force released by energy source 1122. Accordingly, energy source 1122 has released at least some, if not all, of its stored energy (e.g., compression spring is less compressed), and ram assembly 1120, as well as ram 1132, has been distally displaced into a distal position. The distal displacement of ram 1132 urges plunger 1140 in a distal direction, injecting the medicament into the user by dispensing the medicament in medicament chamber 114 through needle 116 and into the user. Although the injection has preferably been completed in this state, injection device 100 is still likely pressed against the injection site since guard 108 remains in a retracted position exposing needle 116. Further, this distal displacement of ram assembly 1120 preferably positions ram assembly 1120 such that it is displayed in window 1020 of housing 102. In an exemplary embodiment, after the distal displacement of ram assembly 1120, it is disposed between medicament container 114 and housing 102 such that it is entirely occluding window 1020 so that only ram assembly 1120 is visible through window 1020, and medicament container 114 is no longer visible (e.g., ram assembly is disposed between medicament container 114 and window 1020). Further, ram assembly 1120 can have a color (as described above) that would be a clear indicator to a user that injection device 1.00 has been used, and different than the other colors visible from the outside of the injector before firing.



FIGS. 12A and 12B show injection device 100 in a “locked-out” state. FIG. 13C shows many of the internal components of injection device 100 in this “locked-out” state without housing 102. The state can be observed, for example, after the user has removed injection device 100 from the injection site. In this state, nothing is restraining guard 108 in the retracted position against the force of spring, and accordingly, guard 108 is distally displaced from the retracted position to the extended position under the force of spring 118, thereby covering needle 116. As guard 108 moves distally from the retracted position to the extended position under the force of spring 118, projections 1086, which are disposed on springs 1088 biased in an outward direction, engage an openings created between proximal surfaces of legs 1110 of sleeve 110 and proximal walls of openings 1128. Accordingly, the association of projections 1086 with the proximal walls of openings 1128 prevents guard 108 from being displaced proximally, and the association of projections 1086 with the proximal surfaces of legs 1110 prevents guard 108 from being displaced distally. Thus, guard 108 is in a locked position, thereby “locking-out” injection device 100 such that needle 116 is covered and guard 108 is locked in place so that a user cannot attempt a subsequent injection. Afterwards, the user may affix cap 104 back onto the distal end of injection device 100.


Advantageously, this “locked-out” state is preferably not dependent on displacement of guard 108, but rather, is preferably dependent on dispensing of the medicament stored in medicament chamber 114 and/or movement of ram assembly 1120. For example, injection device 100 become locked-out in situations where the medicament is inadvertently dispensed, even if guard 108 has not been displaced. Injection device 100 can become locked-out in any instance where energy source 1122 is activated and ram assembly 1120 is distally displaced, causing ram 1132 to displace plunger 1140, thereby dispensing the medicament in medicament chamber 114. This can occur, for example, if injection device 100 is mishandled, dropped, broken, or if housing 102 is defective (e.g., the tolerances of opening 1022 are incorrect, housing 102 is cracked or otherwise compromised, etc.) such that the lateral walls of opening 1022 cannot prevent projections 1134 from splaying outward under the force of energy source 1122. Accordingly, the lock-out feature prevents a user from unknowingly performing an “injection” with an empty injection device 100, even if injection device 100 appears to be new and not used. This can be important in preventing patients from believing that they have administered an injection when in fact the injector was empty.


In an exemplary embodiment, many of the components of injection device 100 are preferably made of a resilient plastic or polymer, or a metal. Preferably, projections 1134 of ram assembly 1120 are oriented so that ram assembly 1120 can be molded using a single mold. For example, as shown in FIGS. 6B and 13C, projections 1134 (which are preferably concentrically symmetrical to each other) can be aligned at an angle relative to the alignment of the other features of ram assembly 1120, such as legs 1130 (which are preferably concentrically symmetrical to each other). For example, as shown in FIG. 17, a single mold can form the portion of ram assembly 1120 designated A (including all the features, components, openings, etc. 1130A), and a single mold can form the portion of ram assembly designated B (including all the features, components, openings, etc. 1130B). Thus, each surface of projections 1134 is preferably accessible along a direction of separating the two molds, and the two molds can be separated linearly without a concave portion of projections 1134 facing orthogonal to the separation direction impeding separation and removal of the molds.


Further, cap 104 can be configured helically so that it can be molded without a hole/opening. For example, cap 104 can include threads 1044 that permit cap 104 to be threadedly removed from a mold. Further, outer housing 102 can include a translucent material to allow users to view the inner workings of injection device 100, and ascertain if it is malfunctioning (e.g., as shown in FIGS. 1A, 7, 8A, 9A, 10A, 11A, 12A, and 16). Additionally, injection device 100 can include various gripping elements, such as ridges, pads, contours, or the like, to make injection device 100 more ergonomic, easy to use, and comfortable to the user. Further, injection device 100 can include markings, such as a sticker, brand markings, drug information, numerals, arrows, or the like, to indicate the steps needed to perform an injection, and areas for promotional markings such as brand and logo designations.



FIG. 18 shows another exemplary embodiment of injection device. As shown in FIG. 18, ram assembly 1120 can include trigger engagement member that takes the form of a seat or ledge 1120b. Seat 1120b can engage a retaining portion, such as ledges 102a, of housing 102 in the pre-fired condition such that the engagement of ledges 102a with the seat 1120b in the pre-fired condition opposes the force of energy source 1122. When a firing of injection device 100 is initiated, ram assembly 1120 can be rotated, for example, via a camming association of guard 108 and ram assembly (such as described with respect to exemplary embodiments above) until recesses 1120a between the seats 1120b align with projections 102a in the firing condition. In the firing condition, the force of energy source 1122 is no longer opposed, allowing ram assembly 1120 to be distally displaced and dispensing the medicament in performing an injection.


All of the references specifically identified in the detailed description section of the present application are expressly incorporated herein in their entirety by reference thereto. The term “about,” as used herein, should generally be understood to refer to both the corresponding number and a range of numbers. Moreover, all numerical ranges herein should be understood to include each whole integer within the range.


While illustrative embodiments of the invention are disclosed herein, it will be appreciated that numerous modifications and other embodiments may be devised by those skilled in the art. For example, the features for the various embodiments can be used in other embodiments. In an alternative embodiment, the hosing can be fixed to the bracket, and the inner portion, defining at least the bottom of the chutes can slide in and out of the housing. Other embodiments can include different mechanisms to cause the rotation of the ram assembly to release it from the retainer portion, such as by direct rotation of the ram by a user, such as via a slide or other element accessible on the outside of the housing, or by a button that is pushed with a finger, or another transmission mechanism to rotate the ram or ram assembly. Therefore, it will be understood that the appended claims are intended to cover all such modifications and embodiments that come within the spirit and scope of the present invention.

Claims
  • 1. An injector, comprising: an injector housing;a container support at least partially within the injector housing, the container support including a projection configured to fix the container support relative to the injector housing;a medicament container associated with the container support;a trigger mechanism including: a trigger member having a retainer portion, anda ram assembly having a ram configured to pressurize the medicament container for expelling a medicament therefrom, the ram assembly further having a trigger engagement member configured to engage the retainer portion of the trigger member in a pre-firing condition;an energy source associated with the ram for powering the ram to expel the medicament; anda user-operable firing-initiation member operable for causing relative movement between the trigger engagement member and the retainer portion from the pre-firing condition to a firing condition in which the trigger engagement member is released from the retainer portion to allow the energy source to fire the ram,wherein the ram assembly includes an opening extending radially through a sidewall of the ram assembly, the opening defined by an opening sidewall and configured to receive at least a portion of the user-operable firing-initiation member.
  • 2. The injector of claim 1, wherein the user-operable firing-initiation member includes a skin-contacting member disposed at a distal end of the injector, the skin-contacting member configured to move proximally with respect to the injector housing when a force is applied to the skin-contacting member, and wherein the user-operable firing-initiation member is associated with the trigger mechanism and is configured to cause axial rotation between the trigger engagement member and the retainer portion from the pre-firing condition to the firing condition upon a proximal movement of the skin-contacting member with respect to the injector housing.
  • 3. The injector of claim 2, wherein the skin-contacting member comprises a first cam, and the ram assembly comprises a second cam, the first cam being operatively associated with the second cam for camming the second cam such that the proximal movement of the skin-contacting member with respect to the injector housing is configured to rotate the ram assembly with respect to the retainer portion so as to position the ram assembly in the firing condition.
  • 4. The injector of claim 1, wherein the user-operable firing-initiation member comprises a skin-contacting member which includes a needle guard that is retractable and is configured to expose a needle connected to the medicament container upon proximal movement of the skin-contacting member.
  • 5. The injector of claim 4, wherein the needle is in fluid communication with the medicament container for injecting the medicament expelled therefrom during firing.
  • 6. The injector of claim 4, wherein the energy source and the needle are configured for jet injecting the medicament through the needle.
  • 7. The injector of claim 6, wherein the energy source is configured to pressurize the medicament to between 90 p.s.i. and 500 p.s.i. to jet inject the medicament.
  • 8. The injector of claim 6, wherein the energy source and the needle are configured for injecting the medicament at an average velocity of at least 1,000 cm/sec within the needle.
  • 9. The injector of claim 1, wherein: the trigger engagement member and the ram are in fixed association, such that rotation of the trigger engagement member rotates the ram; andthe ram assembly is associated with the user-operable firing-initiation member such that operation of the user-operable firing-initiation member rotates the ram assembly within the injector housing to the firing condition.
  • 10. The injector of claim 9, wherein the trigger mechanism comprises a ram holding member that retains the ram assembly against action of the energy source in the pre-firing position, the retainer portion retaining the trigger engagement member, wherein the trigger engagement member is prevented from firing by the ram holding member.
  • 11. The injector of claim 10, wherein in the firing condition, the trigger engagement member is disengaged from the retainer portion, and the energy source overcomes an engagement between the trigger engagement member and the ram holding member.
  • 12. The injector of claim 10, wherein the ram holding member includes a projection that includes a bulge and a groove engaged with the trigger engagement member, and wherein the retainer portion is configured to at least temporarily retain engagement of the trigger engagement member with the bulge and the groove in the pre-firing condition.
  • 13. The injector of claim 1, wherein the ram assembly is of unitary construction.
  • 14. The injector of claim 1, wherein the ram assembly is configured to engage the container support to lock-out the injector after an injection.
  • 15. The injector of claim 14, wherein proximal movement of the user-operable firing-initiation member is blocked by the ram assembly when the injector is locked-out.
  • 16. The injector of claim 1, wherein a pre-firing color gamut is visible from an exterior of the injector in the pre-firing condition, the injector further comprising: a window in the injector housing; andan indicator having an indicator color that is absent from the pre-firing color gamut, which color is hidden from view within the injector housing in the pre-firing condition, wherein in the firing condition, the indicator color is visible through the window from the exterior of the injector for indicating that the injector has been fired.
  • 17. The injector of claim 16, wherein the ram assembly includes the indicator.
  • 18. The injector of claim 17, wherein the ram assembly entirely occludes the window after the injector has been fired.
  • 19. The injector of claim 1, wherein the medicament comprises testosterone.
  • 20. The injector of claim 1, wherein the user-operable firing-initiation member includes a locking projection configured to engage the opening sidewall wherein the locking projection engaged with the opening sidewall prevents movement of the user-operable firing-initiation member relative to the container support.
  • 21. The injector of claim 1, wherein the container support includes a coupling arrangement configured to releasably couple to a cap.
  • 22. The injector of claim 1, wherein the trigger engagement member radially flexes from a first position to a second position as the trigger engagement member moves from the pre-firing condition to the firing condition.
CROSS-REFERENCE TO RELATED APPLICATIONS

This application is the continuation of U.S. patent application Ser. No. 13/889,183, filed 7 May 2013, which in turn claims benefit from U.S. Provisional Patent Application No. 61/643,659, filed 7 May 2012, U.S. Provisional Patent Application No. 61/643,845, filed 7 May 2012, U.S. Provisional Patent Application No. 61/776,283, filed 11 Mar. 2013, and U.S. Provisional Patent Application No. 61/763,395, filed 11 Feb. 2013, each of which is incorporated herein by reference in its entirety.

US Referenced Citations (662)
Number Name Date Kind
547370 Chalefou Oct 1895 A
1465793 Schilling Aug 1923 A
1512294 Marcy Oct 1924 A
1687323 Cook Oct 1928 A
2354649 Bruckner Aug 1944 A
2607344 Brown Aug 1952 A
2645223 Lawshe Jul 1953 A
2648334 Brown Aug 1953 A
2687730 Hein Aug 1954 A
2688967 Huber Sep 1954 A
2699166 Bickinson Jan 1955 A
2717601 Brown Sep 1955 A
2728341 Roehr Dec 1955 A
2737946 Hein, Jr. Mar 1956 A
2813528 Blackman Nov 1957 A
2866458 Mesa et al. Dec 1958 A
2888924 Dunmire Jun 1959 A
2893390 Lockhart Jul 1959 A
3130724 Higgins Apr 1964 A
3166069 Enstrom Jan 1965 A
3375825 Keller Apr 1968 A
3382865 Worrall May 1968 A
3526225 Hayamamachi Sep 1970 A
3557784 Shields Jan 1971 A
3563098 Gley Feb 1971 A
3605744 Dwyer Sep 1971 A
3688765 Gasaway Sep 1972 A
3702609 Steiner Nov 1972 A
3712301 Sarnoff Jan 1973 A
3742948 Post et al. Jul 1973 A
3770026 Isenberg Nov 1973 A
3790048 Luciano et al. Feb 1974 A
3797489 Samoff Mar 1974 A
3797491 Hurschman Mar 1974 A
3811441 Sarnoff May 1974 A
3831814 Butler Aug 1974 A
3848593 Baldwin Nov 1974 A
3882863 Sarnoff et al. May 1975 A
3892237 Steiner Jul 1975 A
3895633 Bartner et al. Jul 1975 A
3946732 Hurscham Mar 1976 A
4031893 Kaplan et al. Jun 1977 A
4067333 Reinhardt et al. Jan 1978 A
4127118 Latorre Nov 1978 A
4171698 Genese Oct 1979 A
4222392 Brennan Sep 1980 A
4227528 Wardlaw Oct 1980 A
4258713 Wardlaw Mar 1981 A
4282986 af Ekenstam et al. Aug 1981 A
4316463 Schmitz et al. Feb 1982 A
4316643 Burk et al. Feb 1982 A
4328802 Curley et al. May 1982 A
4333456 Webb Jun 1982 A
4333458 Margulies et al. Jun 1982 A
4338980 Schwebel et al. Jul 1982 A
4373526 Kling Feb 1983 A
4378015 Wardlaw Mar 1983 A
4411661 Kersten Oct 1983 A
4484910 Sarnoff et al. Nov 1984 A
4529403 Kamstra Jul 1985 A
4553962 Brunet Nov 1985 A
4558690 Joyce Dec 1985 A
4573971 Kamstra Mar 1986 A
4592745 Rex et al. Jun 1986 A
4624660 Mijers et al. Nov 1986 A
4634027 Kanarvogel Jan 1987 A
4661098 Bekkering et al. Apr 1987 A
4662878 Lindmayer May 1987 A
4664653 Sagstetter et al. May 1987 A
4664655 Orentreich et al. May 1987 A
4678461 Mesa Jul 1987 A
4719825 LaHaye et al. Jan 1988 A
4722728 Dixon Feb 1988 A
4774772 Vetter et al. Oct 1988 A
4790824 Morrow et al. Dec 1988 A
4818517 Kwee et al. Apr 1989 A
4820286 van der Wal Apr 1989 A
4822340 Kamstra Apr 1989 A
4830217 Dufresne et al. May 1989 A
4874381 Vetter Oct 1989 A
4883472 Michel Nov 1989 A
4913699 Parsons Apr 1990 A
4915701 Halkyard Apr 1990 A
4929238 Baum May 1990 A
4936833 Sams Jun 1990 A
4940460 Casey et al. Jul 1990 A
4966581 Landau Oct 1990 A
4968302 Schluter et al. Nov 1990 A
4973318 Holm et al. Nov 1990 A
4976701 Ejlersen et al. Dec 1990 A
4982769 Fournier et al. Jan 1991 A
4986816 Steiner et al. Jan 1991 A
5042977 Bechtold et al. Aug 1991 A
5062830 Dunlap Nov 1991 A
5064413 McKinnon et al. Nov 1991 A
5069670 Vetter et al. Dec 1991 A
5078680 Sarnoff Jan 1992 A
5080648 D'Antonio Jan 1992 A
5080649 Vetter Jan 1992 A
5085641 Samoff et al. Feb 1992 A
5085642 Sarnoff et al. Feb 1992 A
5092842 Bechtold et al. Mar 1992 A
5102388 Richmond Apr 1992 A
5102393 Samoff et al. Apr 1992 A
5104380 Holman et al. Apr 1992 A
5114406 Gabriel et al. May 1992 A
5137516 Rand et al. Aug 1992 A
5137528 Crose Aug 1992 A
5139490 Vetter et al. Aug 1992 A
5163907 Szuszkiewicz Nov 1992 A
5176643 Kramer et al. Jan 1993 A
5180370 Gillespie Jan 1993 A
5185985 Vetter et al. Feb 1993 A
5195983 Boese Mar 1993 A
5221348 Masano Jun 1993 A
5226895 Harris Jul 1993 A
5232459 Hjertman Aug 1993 A
5256142 Colavecchio Oct 1993 A
5263934 Haak Nov 1993 A
5271744 Kramer et al. Dec 1993 A
5279543 Glikfeld et al. Jan 1994 A
5279576 Loo et al. Jan 1994 A
5279585 Balkwill Jan 1994 A
5279586 Balkwill Jan 1994 A
5281198 Haber et al. Jan 1994 A
5290228 Uemura et al. Mar 1994 A
5295965 Wilmot Mar 1994 A
5300030 Crossman et al. Apr 1994 A
5304128 Haber et al. Apr 1994 A
5304152 Sams Apr 1994 A
5308341 Chanoch May 1994 A
5318522 D'Antonio Jun 1994 A
5320603 Vetter et al. Jun 1994 A
5330431 Herskowitz Jul 1994 A
5332399 Grabenkort et al. Jul 1994 A
5334144 Alchas et al. Aug 1994 A
5342308 Boschetti Aug 1994 A
5350367 Stiehl et al. Sep 1994 A
5354286 Mesa et al. Oct 1994 A
5358489 Wyrick Oct 1994 A
RE34845 Vetter et al. Jan 1995 E
5391151 Wilmot Feb 1995 A
5405362 Kramer et al. Apr 1995 A
5415648 Malay et al. May 1995 A
5425715 Dalling et al. Jun 1995 A
5451210 Kramer et al. Sep 1995 A
5478316 Bitdinger et al. Dec 1995 A
5505694 Hubbard et al. Apr 1996 A
5514097 Knauer May 1996 A
5514107 Haber et al. May 1996 A
5540664 Wyrick Jul 1996 A
5542760 Chanoch et al. Aug 1996 A
5544234 Terajima et al. Aug 1996 A
5549561 Hjertman Aug 1996 A
5554134 Bonnichsen Sep 1996 A
5562625 Stefancin, Jr. Oct 1996 A
5567160 Massino Oct 1996 A
5569190 D'Antonio Oct 1996 A
5569192 van der Wal Oct 1996 A
5569236 Kriesel Oct 1996 A
5573042 De Haen Nov 1996 A
5593388 Phillips Jan 1997 A
5599302 Lilley et al. Feb 1997 A
5599309 Marshall et al. Feb 1997 A
5605542 Tanaka et al. Feb 1997 A
5637094 Stewart, Jr. et al. Jun 1997 A
5637100 Sudo Jun 1997 A
5649912 Peterson Jul 1997 A
5658259 Pearson et al. Aug 1997 A
5665071 Wyrick Sep 1997 A
5688251 Chanoch Nov 1997 A
5695472 Wyrick Dec 1997 A
5704911 Parsons Jan 1998 A
5725508 Chanoch et al. Mar 1998 A
5730723 Castellano et al. Mar 1998 A
5743889 Sams Apr 1998 A
5769138 Sadowski et al. Jun 1998 A
5785691 Vetter et al. Jul 1998 A
5788670 Reinhard et al. Aug 1998 A
5801057 Smart et al. Sep 1998 A
5807309 Lundquist et al. Sep 1998 A
5820602 Kovelman et al. Oct 1998 A
5820622 Gross et al. Oct 1998 A
5827232 Chanoch et al. Oct 1998 A
5836911 Marzynski et al. Nov 1998 A
5843036 Olive et al. Dec 1998 A
5846233 Lilley et al. Dec 1998 A
5851197 Marano et al. Dec 1998 A
5851198 Castellano et al. Dec 1998 A
5860456 Bydlon et al. Jan 1999 A
5865795 Schiff et al. Feb 1999 A
5865799 Tanaka et al. Feb 1999 A
5868711 Kramer et al. Feb 1999 A
5873857 Kriesel Feb 1999 A
5875976 Nelson et al. Mar 1999 A
5879327 DeFarges et al. Mar 1999 A
5891085 Lilley et al. Apr 1999 A
5891086 Weston Apr 1999 A
5893842 Imbert Apr 1999 A
5919159 Lilley et al. Jul 1999 A
5921966 Bendek et al. Jul 1999 A
5925017 Kriesel et al. Jul 1999 A
5928205 Marshall Jul 1999 A
5935949 White Aug 1999 A
5951528 Parkin Sep 1999 A
5957897 Jeffrey Sep 1999 A
5960797 Kramer et al. Oct 1999 A
5989227 Vetter et al. Nov 1999 A
6004297 Steenfeldt-Jensen et al. Dec 1999 A
6045534 Jacobson et al. Apr 2000 A
6056716 D'Antonio et al. May 2000 A
6077247 Marshall et al. Jun 2000 A
6083201 Skinkle Jul 2000 A
6090070 Hager et al. Jul 2000 A
6099504 Gross et al. Aug 2000 A
6123684 Deboer et al. Sep 2000 A
6132395 Landau et al. Oct 2000 A
6159181 Crossman et al. Dec 2000 A
6171276 Lippe et al. Jan 2001 B1
6203529 Gabriel et al. Mar 2001 B1
6210369 Wilmot et al. Apr 2001 B1
6221046 Burroughs et al. Apr 2001 B1
6221053 Walters et al. Apr 2001 B1
6223408 Vetter et al. May 2001 B1
6231540 Smedegaard May 2001 B1
6241709 Bechtold et al. Jun 2001 B1
6245347 Zhang et al. Jun 2001 B1
6258078 Thilly Jul 2001 B1
6264629 Landau Jul 2001 B1
6270479 Bergens et al. Aug 2001 B1
6309371 Deboer et al. Oct 2001 B1
6319224 Stout et al. Nov 2001 B1
6371939 Bergens et al. Apr 2002 B2
6383168 Landau et al. May 2002 B1
6391003 Lesch, Jr. May 2002 B1
6406456 Slate et al. Jun 2002 B1
6428528 Sadowski et al. Aug 2002 B2
6471669 Landau Oct 2002 B2
6494865 Alchas Dec 2002 B1
6517517 Farrugia et al. Feb 2003 B1
6530904 Edwards et al. Mar 2003 B1
6544234 Gabriel Apr 2003 B1
6562006 Hjertman et al. May 2003 B1
6565553 Sadowski et al. May 2003 B2
6568259 Saheki et al. May 2003 B2
6569123 Alchas et al. May 2003 B2
6569143 Alchas et al. May 2003 B2
6584910 Plass Jul 2003 B1
6589210 Rolfe Jul 2003 B1
6607508 Knauer Aug 2003 B2
6620137 Kirchhofer et al. Sep 2003 B2
6641561 Hill et al. Nov 2003 B1
6645170 Landau Nov 2003 B2
6656150 Hill et al. Dec 2003 B2
6673035 Rice et al. Jan 2004 B1
6682504 Nelson et al. Jan 2004 B2
6689092 Zierenberg et al. Feb 2004 B2
6706000 Perez et al. Mar 2004 B2
6746429 Sadowski et al. Jun 2004 B2
6767336 Kaplan Jul 2004 B1
6805686 Fathallah et al. Oct 2004 B1
6830560 Gross et al. Dec 2004 B1
6899698 Sams May 2005 B2
6932793 Marshall et al. Aug 2005 B1
6932794 Giambattista et al. Aug 2005 B2
6936032 Bush, Jr. et al. Aug 2005 B1
6969370 Langley et al. Nov 2005 B2
6969372 Halseth Nov 2005 B1
6979316 Rubin et al. Dec 2005 B1
6986758 Schiffmann Jan 2006 B2
6997901 Popovsky Feb 2006 B2
7018364 Giambattista et al. Mar 2006 B2
7066907 Crossman et al. Jun 2006 B2
7112187 Karlsson Sep 2006 B2
7118552 Shaw et al. Oct 2006 B2
7118553 Scherer Oct 2006 B2
7169132 Bendek et al. Jan 2007 B2
7195616 Diller et al. Mar 2007 B2
7218962 Freyman May 2007 B2
7220247 Shaw et al. May 2007 B2
7247149 Beyerlein Jul 2007 B2
7291132 DeRuntz et al. Nov 2007 B2
7292885 Scott et al. Nov 2007 B2
7297136 Wyrick Nov 2007 B2
7341575 Rice et al. Mar 2008 B2
7361160 Hommann et al. Apr 2008 B2
7390314 Stutz, Jr. et al. Jun 2008 B2
7390319 Friedman Jun 2008 B2
7407492 Gurtner Aug 2008 B2
7416540 Edwards et al. Aug 2008 B2
7442185 Amark et al. Oct 2008 B2
7449012 Young et al. Nov 2008 B2
7488308 Lesch, Jr. Feb 2009 B2
7488313 Segal et al. Feb 2009 B2
7488314 Segal et al. Feb 2009 B2
7500964 Shaw et al. Mar 2009 B2
7517342 Scott et al. Apr 2009 B2
7519418 Scott et al. Apr 2009 B2
7544188 Edwards et al. Jun 2009 B2
7547293 Williamson et al. Jun 2009 B2
7569035 Wilmot et al. Aug 2009 B1
7611491 Pickhard Nov 2009 B2
7621887 Griffiths et al. Nov 2009 B2
7621891 Wyrick Nov 2009 B2
7635348 Raven et al. Dec 2009 B2
7635350 Scherer Dec 2009 B2
7637891 Wall Dec 2009 B2
7648482 Edwards et al. Jan 2010 B2
7648483 Edwards et al. Jan 2010 B2
7654983 De La Sema et al. Feb 2010 B2
7658724 Rubin et al. Feb 2010 B2
7670314 Wall et al. Mar 2010 B2
7704237 Fisher et al. Apr 2010 B2
7717877 Lavi et al. May 2010 B2
7722595 Pettis et al. May 2010 B2
7731686 Edwards et al. Jun 2010 B2
7731690 Edwards et al. Jun 2010 B2
7736333 Gillespie, III Jun 2010 B2
7744582 Sadowski et al. Jun 2010 B2
7749194 Edwards et al. Jul 2010 B2
7749195 Hommann Jul 2010 B2
7762996 Palasis Jul 2010 B2
7776015 Sadowski et al. Aug 2010 B2
7794432 Young et al. Sep 2010 B2
7811254 Wilmot et al. Oct 2010 B2
7862543 Potter et al. Jan 2011 B2
7896841 Wall et al. Mar 2011 B2
7901377 Harrison et al. Mar 2011 B1
7905352 Wyrick Mar 2011 B2
7905866 Haider et al. Mar 2011 B2
7918823 Edwards et al. Apr 2011 B2
7927303 Wyrick Apr 2011 B2
7931618 Wyrick Apr 2011 B2
7947017 Edwards et al. May 2011 B2
RE42463 Landau Jun 2011 E
7955304 Guillermo Jun 2011 B2
7967772 McKenzie et al. Jun 2011 B2
7988675 Gillespie, III et al. Aug 2011 B2
8016774 Freeman et al. Sep 2011 B2
8016788 Edwards et al. Sep 2011 B2
8021335 Lesch, Jr. Sep 2011 B2
8048035 Mesa et al. Nov 2011 B2
8048037 Kohlbrenner et al. Nov 2011 B2
8057427 Griffiths et al. Nov 2011 B2
8066659 Joshi et al. Nov 2011 B2
8083711 Enggaard Dec 2011 B2
8100865 Spofforth Jan 2012 B2
8105272 Williamson et al. Jan 2012 B2
8105281 Edwards et al. Jan 2012 B2
8110209 Prestrelski et al. Feb 2012 B2
8123719 Edwards et al. Feb 2012 B2
8123724 Gillespie, III Feb 2012 B2
8162873 Muto et al. Apr 2012 B2
8162886 Sadowski et al. Apr 2012 B2
8167840 Matusch May 2012 B2
8167866 Klein May 2012 B2
8177758 Brooks, Jr. et al. May 2012 B2
8187224 Wyrick May 2012 B2
8216180 Tschirren et al. Jul 2012 B2
8216192 Burroughs et al. Jul 2012 B2
8226618 Geertsen Jul 2012 B2
8226631 Boyd et al. Jul 2012 B2
8233135 Jansen et al. Jul 2012 B2
8235952 Wikner Aug 2012 B2
8246577 Schrul et al. Aug 2012 B2
8251947 Kramer et al. Aug 2012 B2
8257318 Thogersen et al. Sep 2012 B2
8257319 Plumptre Sep 2012 B2
8267899 Moller Sep 2012 B2
8267900 Harms et al. Sep 2012 B2
8273798 Bausch et al. Sep 2012 B2
8275454 Adachi et al. Sep 2012 B2
8276583 Farieta et al. Oct 2012 B2
8277412 Kronestedt Oct 2012 B2
8277413 Kirchhofer Oct 2012 B2
8298175 Hirschel et al. Oct 2012 B2
8298194 Moller Oct 2012 B2
8300852 Terada Oct 2012 B2
RE43834 Steenfeldt-Jensen et al. Nov 2012 E
8308232 Zamperla et al. Nov 2012 B2
8308695 Laiosa Nov 2012 B2
8313466 Edwards et al. Nov 2012 B2
8317757 Plumptre Nov 2012 B2
8323237 Radmer et al. Dec 2012 B2
8333739 Moller Dec 2012 B2
8337472 Edginton et al. Dec 2012 B2
8343103 Moser Jan 2013 B2
8343109 Marshall et al. Jan 2013 B2
8348905 Radmer et al. Jan 2013 B2
8353878 Moller et al. Jan 2013 B2
8357120 Moller et al. Jan 2013 B2
8357125 Grunhut et al. Jan 2013 B2
8361036 Moller et al. Jan 2013 B2
8366680 Raab Feb 2013 B2
8372031 Elmen et al. Feb 2013 B2
8372042 Wieselblad Feb 2013 B2
8376993 Cox et al. Feb 2013 B2
8398593 Eich et al. Mar 2013 B2
8409149 Hommann et al. Apr 2013 B2
8435215 Arby et al. May 2013 B2
8496619 Kramer Jul 2013 B2
9364610 KraMer Jun 2016 B2
9364611 KraMer Jun 2016 B2
9446195 Kramer Sep 2016 B2
20010039394 Weston Nov 2001 A1
20010049496 Kirchhofer et al. Dec 2001 A1
20020007149 Nelson et al. Jan 2002 A1
20020045866 Sadowski et al. Apr 2002 A1
20020173752 Polzin Nov 2002 A1
20020183690 Arnisolle Dec 2002 A1
20020188251 Staylor et al. Dec 2002 A1
20030040697 Pass et al. Feb 2003 A1
20030083621 Shaw et al. May 2003 A1
20030105430 Lavi et al. Jun 2003 A1
20030130619 Safabash et al. Jul 2003 A1
20030158523 Hjertman et al. Aug 2003 A1
20030171717 Farrugia et al. Sep 2003 A1
20030229330 Hickle Dec 2003 A1
20030236502 De La Serna et al. Dec 2003 A1
20040039336 Amark et al. Feb 2004 A1
20040039337 Letzing Feb 2004 A1
20040097783 Peters et al. May 2004 A1
20040097883 Roe May 2004 A1
20040143213 Hunter et al. Jul 2004 A1
20040220524 Sadwoski et al. Nov 2004 A1
20040267207 Veasey et al. Dec 2004 A1
20040267355 Scott et al. Dec 2004 A1
20050020979 Westbye et al. Jan 2005 A1
20050027255 Lavi et al. Feb 2005 A1
20050033234 Sadowski et al. Feb 2005 A1
20050080377 Sadowski et al. Apr 2005 A1
20050101919 Brunnberg May 2005 A1
20050165360 Stamp Jul 2005 A1
20050165363 Judson et al. Jul 2005 A1
20050209569 Ishikawa et al. Sep 2005 A1
20050215955 Slawson Sep 2005 A1
20050240145 Scott et al. Oct 2005 A1
20050256499 Pettis et al. Nov 2005 A1
20050261634 Karlsson Nov 2005 A1
20050273054 Asch Dec 2005 A1
20060025747 Sullivan et al. Feb 2006 A1
20060106362 Pass et al. May 2006 A1
20060129122 Wyrick Jun 2006 A1
20060173408 Wyrick Aug 2006 A1
20060224124 Scherer Oct 2006 A1
20060258988 Keitel et al. Nov 2006 A1
20060258990 Weber Nov 2006 A1
20070017533 Wyrick Jan 2007 A1
20070025890 Joshi et al. Feb 2007 A1
20070027430 Hommann Feb 2007 A1
20070088288 Barron et al. Apr 2007 A1
20070093775 Daly Apr 2007 A1
20070100288 Bozeman et al. May 2007 A1
20070123818 Griffiths et al. May 2007 A1
20070123829 Atterbury et al. May 2007 A1
20070129686 Daily et al. Jun 2007 A1
20070129687 Marshall et al. Jun 2007 A1
20070185432 Etheredge et al. Aug 2007 A1
20070191784 Jacobs et al. Aug 2007 A1
20070219498 Malone et al. Sep 2007 A1
20080059133 Edwards et al. Mar 2008 A1
20080154199 Wyrick Jun 2008 A1
20080154200 Lesch Jun 2008 A1
20080185069 Clark Aug 2008 A1
20080262427 Hommann Oct 2008 A1
20080262436 Olson Oct 2008 A1
20080262445 Hsu et al. Oct 2008 A1
20090124981 Evans May 2009 A1
20090124997 Pettis et al. May 2009 A1
20090204062 Muto et al. Aug 2009 A1
20090254027 Moller Oct 2009 A1
20090254035 Kohlbrenner et al. Oct 2009 A1
20090292240 Kramer et al. Nov 2009 A1
20090299278 Lesch et al. Dec 2009 A1
20090304812 Staniforth et al. Dec 2009 A1
20090312705 Grunhut Dec 2009 A1
20090318361 Noera et al. Dec 2009 A1
20100016326 Will Jan 2010 A1
20100036318 Raday et al. Feb 2010 A1
20100049125 James et al. Feb 2010 A1
20100056989 McKay Mar 2010 A1
20100069845 Marshall et al. Mar 2010 A1
20100076378 Runfola Mar 2010 A1
20100076400 Wall Mar 2010 A1
20100087847 Hong Apr 2010 A1
20100094214 Abry et al. Apr 2010 A1
20100094324 Huang et al. Apr 2010 A1
20100100039 Wyrick Apr 2010 A1
20100114058 Weitzel et al. May 2010 A1
20100121272 Marshall et al. May 2010 A1
20100137798 Streit et al. Jun 2010 A1
20100152699 Ferrari et al. Jun 2010 A1
20100152702 Vigil et al. Jun 2010 A1
20100160894 Julian Jun 2010 A1
20100168677 Gabriel et al. Jul 2010 A1
20100174268 Wilmot et al. Jul 2010 A1
20100191217 Hommann et al. Jul 2010 A1
20100204678 Imran Aug 2010 A1
20100217105 Yodfat et al. Aug 2010 A1
20100228193 Wyrick Sep 2010 A1
20100249746 Klein Sep 2010 A1
20100256570 Maritan Oct 2010 A1
20100258631 Rueblinger et al. Oct 2010 A1
20100262082 Brooks et al. Oct 2010 A1
20100262083 Grunhut et al. Oct 2010 A1
20100268170 Carrel et al. Oct 2010 A1
20100274198 Bechtold Oct 2010 A1
20100274273 Schraga et al. Oct 2010 A1
20100288593 Chiesa et al. Nov 2010 A1
20100292643 Wilmot et al. Nov 2010 A1
20100292653 Maritan Nov 2010 A1
20100298780 Laiosa Nov 2010 A1
20100312196 Hirschel et al. Dec 2010 A1
20100318035 Edwards et al. Dec 2010 A1
20100318037 Young et al. Dec 2010 A1
20100324480 Chun Dec 2010 A1
20110021989 Janek et al. Jan 2011 A1
20110034879 Crow Feb 2011 A1
20110054414 Shang et al. Mar 2011 A1
20110077599 Wozencroft Mar 2011 A1
20110087192 Uhland et al. Apr 2011 A1
20110098655 Jennings et al. Apr 2011 A1
20110098656 Burnell et al. Apr 2011 A1
20110125076 Kraft et al. May 2011 A1
20110125100 Schwirtz et al. May 2011 A1
20110137246 Cali et al. Jun 2011 A1
20110137247 Mesa et al. Jun 2011 A1
20110144594 Sund et al. Jun 2011 A1
20110190725 Pettis et al. Aug 2011 A1
20110196300 Edwards et al. Aug 2011 A1
20110196311 Bicknell et al. Aug 2011 A1
20110224620 Johansen et al. Sep 2011 A1
20110238003 Bruno-Raimondi et al. Sep 2011 A1
20110269750 Kley et al. Nov 2011 A1
20110319864 Beller et al. Dec 2011 A1
20120004608 Lesch, Jr. Jan 2012 A1
20120016296 Cleathero Jan 2012 A1
20120046609 Mesa et al. Feb 2012 A1
20120053563 Du Mar 2012 A1
20120059319 Segal Mar 2012 A1
20120071829 Edwards et al. Mar 2012 A1
20120095443 Ferrari et al. Apr 2012 A1
20120101475 Wilmot et al. Apr 2012 A1
20120116318 Edwards et al. May 2012 A1
20120123350 Giambattista et al. May 2012 A1
20120123385 Edwards et al. May 2012 A1
20120130318 Young May 2012 A1
20120130342 Cleathero May 2012 A1
20120136303 Cleathero May 2012 A1
20120136318 Lanin et al. May 2012 A1
20120143144 Young Jun 2012 A1
20120157931 Nzike Jun 2012 A1
20120157965 Wotton et al. Jun 2012 A1
20120157966 Wotton et al. Jun 2012 A1
20120172809 Plumptre Jul 2012 A1
20120172811 Enggaard et al. Jul 2012 A1
20120172812 Plumptre et al. Jul 2012 A1
20120172813 Plumptre et al. Jul 2012 A1
20120172814 Plumptre et al. Jul 2012 A1
20120172815 Holmqvist Jul 2012 A1
20120172816 Boyd et al. Jul 2012 A1
20120172818 Harms et al. Jul 2012 A1
20120172885 Drapeau et al. Jul 2012 A1
20120179100 Sadowski et al. Jul 2012 A1
20120179137 Bartlett et al. Jul 2012 A1
20120184900 Marshall et al. Jul 2012 A1
20120184917 Bom et al. Jul 2012 A1
20120184918 Bostrom Jul 2012 A1
20120186075 Edginton Jul 2012 A1
20120191048 Eaton Jul 2012 A1
20120191049 Harms et al. Jul 2012 A1
20120197209 Bicknell et al. Aug 2012 A1
20120197213 Kohlbrenner et al. Aug 2012 A1
20120203184 Selz et al. Aug 2012 A1
20120203185 Kristensen et al. Aug 2012 A1
20120203186 Vogt et al. Aug 2012 A1
20120209192 Alexandersson Aug 2012 A1
20120209200 Jones et al. Aug 2012 A1
20120209210 Plumptre et al. Aug 2012 A1
20120209211 Plumptre et al. Aug 2012 A1
20120209212 Plumptre et al. Aug 2012 A1
20120215162 Nielsen et al. Aug 2012 A1
20120215176 Veasey et al. Aug 2012 A1
20120220929 Nagel et al. Aug 2012 A1
20120220941 Jones Aug 2012 A1
20120220953 Holmqvist Aug 2012 A1
20120220954 Cowe Aug 2012 A1
20120226226 Edwards et al. Sep 2012 A1
20120230620 Holdgate et al. Sep 2012 A1
20120232517 Saiki Sep 2012 A1
20120245516 Tschirren et al. Sep 2012 A1
20120245532 Frantz et al. Sep 2012 A1
20120253274 Karlsson et al. Oct 2012 A1
20120253287 Giambattista et al. Oct 2012 A1
20120253288 Dasbach et al. Oct 2012 A1
20120253289 Cleathero Oct 2012 A1
20120253290 Geertsen Oct 2012 A1
20120253314 Harish et al. Oct 2012 A1
20120259285 Schabbach et al. Oct 2012 A1
20120265153 Jugl et al. Oct 2012 A1
20120267761 Kim et al. Oct 2012 A1
20120271233 Bruggemann et al. Oct 2012 A1
20120271243 Plumptre et al. Oct 2012 A1
20120277724 Larsen et al. Nov 2012 A1
20120283645 Veasey et al. Nov 2012 A1
20120283648 Veasey et al. Nov 2012 A1
20120283649 Veasey et al. Nov 2012 A1
20120283650 MacDonald et al. Nov 2012 A1
20120283651 Veasey et al. Nov 2012 A1
20120283652 MacDonald et al. Nov 2012 A1
20120283654 MacDonald et al. Nov 2012 A1
20120283660 Jones et al. Nov 2012 A1
20120283661 Jugl et al. Nov 2012 A1
20120289907 Veasey et al. Nov 2012 A1
20120289908 Kouyoumjian et al. Nov 2012 A1
20120289909 Raab et al. Nov 2012 A1
20120289929 Boyd et al. Nov 2012 A1
20120291778 Nagel et al. Nov 2012 A1
20120296276 Nicholls et al. Nov 2012 A1
20120296287 Veasey et al. Nov 2012 A1
20120302989 Kramer et al. Nov 2012 A1
20120302992 Brooks et al. Nov 2012 A1
20120310156 Karlsson et al. Dec 2012 A1
20120310206 Kouyoumjian et al. Dec 2012 A1
20120310208 Kirchhofer Dec 2012 A1
20120310289 Bottlang et al. Dec 2012 A1
20120316508 Kirchhofer Dec 2012 A1
20120323177 Adams et al. Dec 2012 A1
20120323186 Karlsen et al. Dec 2012 A1
20120325865 Forstreuter et al. Dec 2012 A1
20120330228 Day et al. Dec 2012 A1
20130006191 Jugl et al. Jan 2013 A1
20130006192 Teucher et al. Jan 2013 A1
20130006193 Veasey et al. Jan 2013 A1
20130006310 Bottlang et al. Jan 2013 A1
20130012871 Pommereu Jan 2013 A1
20130012884 Pommerau et al. Jan 2013 A1
20130012885 Bode et al. Jan 2013 A1
20130018310 Boyd et al. Jan 2013 A1
20130018313 Kramer et al. Jan 2013 A1
20130018317 Bobroff et al. Jan 2013 A1
20130018323 Boyd et al. Jan 2013 A1
20130018327 Dasbach et al. Jan 2013 A1
20130018328 Jugl et al. Jan 2013 A1
20130023830 Bode Jan 2013 A1
20130030367 Wotton et al. Jan 2013 A1
20130030378 Jugl et al. Jan 2013 A1
20130030383 Keitel Jan 2013 A1
20130030409 Macdonald et al. Jan 2013 A1
20130035641 Moller et al. Feb 2013 A1
20130035642 Daniel Feb 2013 A1
20130035644 Giambattista et al. Feb 2013 A1
20130035645 Bicknell et al. Feb 2013 A1
20130035647 Veasey et al. Feb 2013 A1
20130041321 Cross et al. Feb 2013 A1
20130041324 Daniel Feb 2013 A1
20130041325 Helmer et al. Feb 2013 A1
20130041327 Daniel Feb 2013 A1
20130041328 Daniel Feb 2013 A1
20130041347 Daniel Feb 2013 A1
20130060231 Adlon et al. Mar 2013 A1
20140228769 Karlsson Aug 2014 A1
Foreign Referenced Citations (491)
Number Date Country
00081651 Oct 2012 AR
082053 Nov 2012 AR
2007253481 Nov 2007 AU
2007301890 Apr 2008 AU
2008231897 Oct 2008 AU
2008309660 Apr 2009 AU
2009217376 Oct 2009 AU
2009272992 Jan 2010 AU
2009299888 Apr 2010 AU
2009326132 Aug 2011 AU
2009326321 Aug 2011 AU
2009326322 Aug 2011 AU
2009326323 Aug 2011 AU
2009326324 Aug 2011 AU
2009326325 Aug 2011 AU
2009341040 Sep 2011 AU
2010233924 Nov 2011 AU
2010239762 Dec 2011 AU
2010242096 Dec 2011 AU
2010254627 Jan 2012 AU
2010260568 Feb 2012 AU
2010260569 Feb 2012 AU
2010287033 Apr 2012 AU
2010303987 May 2012 AU
2010332857 Jul 2012 AU
2010332862 Jul 2012 AU
2010337136 Jul 2012 AU
2010338469 Jul 2012 AU
2010314315 Aug 2012 AU
2011212490 Aug 2012 AU
2011212556 Aug 2012 AU
2011212558 Aug 2012 AU
2011212561 Aug 2012 AU
2011212564 Aug 2012 AU
2011212566 Aug 2012 AU
2011212567 Aug 2012 AU
2011214922 Aug 2012 AU
2011221472 Aug 2012 AU
2011231688 Sep 2012 AU
2011231691 Sep 2012 AU
2011224884 Oct 2012 AU
2011231570 Oct 2012 AU
2011231697 Oct 2012 AU
2011233733 Oct 2012 AU
2011234479 Oct 2012 AU
2011238967 Nov 2012 AU
2011244232 Nov 2012 AU
2011244236 Nov 2012 AU
2011244237 Nov 2012 AU
2011249098 Nov 2012 AU
2011262408 Dec 2012 AU
2011270934 Jan 2013 AU
2011273721 Jan 2013 AU
2011273722 Jan 2013 AU
2011273723 Jan 2013 AU
2011273724 Jan 2013 AU
2011273725 Jan 2013 AU
2011273726 Jan 2013 AU
2011273727 Jan 2013 AU
2011273728 Jan 2013 AU
0208013 Mar 2004 BR
0308262 Jan 2005 BR
PI0712805 Oct 2012 BR
PI0713802-4 Nov 2012 BR
0214721 Dec 2012 BR
2552177 Jul 1999 CA
2689022 Nov 2002 CA
2473371 Jul 2003 CA
2557897 Oct 2005 CA
02702412 Dec 2008 CA
101094700 Dec 2007 CN
101128231 Feb 2008 CN
101184520 May 2008 CN
101400394 Apr 2009 CN
101405582 Apr 2009 CN
101479000 Jul 2009 CN
101511410 Aug 2009 CN
101516421 Aug 2009 CN
101557849 Oct 2009 CN
101563123 Oct 2009 CN
101563124 Oct 2009 CN
101594898 Dec 2009 CN
101600468 Dec 2009 CN
101605569 Dec 2009 CN
101610804 Dec 2009 CN
101626796 Jan 2010 CN
101678166 Mar 2010 CN
101678172 Mar 2010 CN
101678173 Mar 2010 CN
101687078 Mar 2010 CN
101687079 Mar 2010 CN
101687080 Mar 2010 CN
101715371 May 2010 CN
101909673 Dec 2010 CN
101912650 Dec 2010 CN
101939034 Jan 2011 CN
101939036 Jan 2011 CN
102548599 Jul 2012 CN
102548601 Jul 2012 CN
102548602 Jul 2012 CN
102573955 Jul 2012 CN
102573958 Jul 2012 CN
102573960 Jul 2012 CN
102573963 Jul 2012 CN
102630172 Aug 2012 CN
102630173 Aug 2012 CN
102630174 Aug 2012 CN
102639170 Aug 2012 CN
102639171 Aug 2012 CN
102648014 Aug 2012 CN
102655899 Sep 2012 CN
102665800 Sep 2012 CN
102665802 Sep 2012 CN
102686255 Sep 2012 CN
102686256 Sep 2012 CN
102686258 Sep 2012 CN
102695531 Sep 2012 CN
102695532 Sep 2012 CN
102711878 Oct 2012 CN
102727965 Oct 2012 CN
102740907 Oct 2012 CN
102753222 Oct 2012 CN
102753223 Oct 2012 CN
102753224 Oct 2012 CN
102753227 Oct 2012 CN
102770170 Nov 2012 CN
102770173 Nov 2012 CN
102781499 Nov 2012 CN
102781500 Nov 2012 CN
102802699 Nov 2012 CN
102802702 Nov 2012 CN
102802703 Nov 2012 CN
102665801 Dec 2012 CN
102821801 Dec 2012 CN
102821802 Dec 2012 CN
102821805 Dec 2012 CN
102834133 Dec 2012 CN
10286399 Jan 2013 CN
102895718 Jan 2013 CN
102905613 Jan 2013 CN
102905742 Jan 2013 CN
102905743 Jan 2013 CN
102905744 Jan 2013 CN
102905745 Jan 2013 CN
102917738 Feb 2013 CN
102917743 Feb 2013 CN
102006041809 Mar 2008 DE
202011110155 Dec 2012 DE
1646844 Dec 2009 DK
2229201 Jul 2012 DK
2023982 Oct 2012 DK
2274032 Oct 2012 DK
02346552 Nov 2012 DK
1888148 Jan 2013 DK
2288400 Jan 2013 DK
2373361 Jan 2013 DK
1885414 Feb 2013 DK
2174682 Feb 2013 DK
2310073 Feb 2013 DK
25844 Sep 2012 EG
0072057 Feb 1983 EP
0103664 Mar 1984 EP
1752174 Mar 1986 EP
245895 Nov 1987 EP
255044 Feb 1988 EP
361668 Apr 1990 EP
0518416 Dec 1992 EP
525525 Feb 1993 EP
1067823 Jan 2001 EP
1161961 Dec 2001 EP
1307012 May 2003 EP
1518575 Mar 2005 EP
1140260 Aug 2005 EP
1944050 Jul 2008 EP
2174682 Apr 2010 EP
2258424 Dec 2010 EP
2258425 Dec 2010 EP
02275158 Jan 2011 EP
2364742 Sep 2011 EP
2393062 Dec 2011 EP
2471564 Jul 2012 EP
02477681 Jul 2012 EP
02484395 Aug 2012 EP
2526987 Nov 2012 EP
02529773 Dec 2012 EP
02529774 Dec 2012 EP
02529775 Dec 2012 EP
2549789 Jan 2013 EP
02385630 Jul 2012 ES
2389866 Nov 2012 ES
2392667 Dec 2012 ES
02393173 Dec 2012 ES
2394556 Feb 2013 ES
2506161 Nov 1982 FR
2635009 Feb 1990 FR
677523 Aug 1952 GB
1181037 Feb 1970 GB
1216813 Dec 1970 GB
2463034 Mar 2010 GB
171247 Aug 2012 IL
198750 Oct 2012 IL
10-507935 Aug 1998 JP
11-347121 Dec 1999 JP
2000-245839 Sep 2000 JP
2001-523485 Nov 2001 JP
5016490 May 2008 JP
5026411 Nov 2008 JP
5033792 Nov 2008 JP
5074397 Feb 2009 JP
2009-529395 Aug 2009 JP
5066177 Sep 2009 JP
5039135 Nov 2009 JP
5044625 Dec 2009 JP
2010-005414 Jan 2010 JP
2010-046507 Mar 2010 JP
4970282 Jul 2012 JP
4970286 Jul 2012 JP
4972147 Jul 2012 JP
4977209 Jul 2012 JP
4977252 Jul 2012 JP
4979686 Jul 2012 JP
4982722 Jul 2012 JP
2012515566 Jul 2012 JP
2012515585 Jul 2012 JP
2012515587 Jul 2012 JP
2012516168 Jul 2012 JP
2012516736 Jul 2012 JP
2012516737 Jul 2012 JP
4990151 Aug 2012 JP
4992147 Aug 2012 JP
4994370 Aug 2012 JP
5001001 Aug 2012 JP
2012143646 Aug 2012 JP
2012148198 Aug 2012 JP
2012519508 Aug 2012 JP
2012519511 Aug 2012 JP
2012519514 Aug 2012 JP
2012176295 Sep 2012 JP
2012183322 Sep 2012 JP
2012520128 Sep 2012 JP
2012521821 Sep 2012 JP
2012521825 Sep 2012 JP
2012521826 Sep 2012 JP
2012521827 Sep 2012 JP
2012521828 Sep 2012 JP
2012521829 Sep 2012 JP
2012521830 Sep 2012 JP
2012521831 Sep 2012 JP
2012521834 Sep 2012 JP
2012522547 Sep 2012 JP
2012-525172 Oct 2012 JP
2012-525180 Oct 2012 JP
2012-525185 Oct 2012 JP
2012523876 Oct 2012 JP
2012525200 Oct 2012 JP
5084825 Nov 2012 JP
2012232151 Nov 2012 JP
2012258628 Nov 2012 JP
2012528618 Nov 2012 JP
2012528619 Nov 2012 JP
2012528620 Nov 2012 JP
2012528621 Nov 2012 JP
2012528622 Nov 2012 JP
2012528623 Nov 2012 JP
2012528624 Nov 2012 JP
2012528625 Nov 2012 JP
2012528626 Nov 2012 JP
2012528627 Nov 2012 JP
2012528629 Nov 2012 JP
2012528630 Nov 2012 JP
2012528631 Nov 2012 JP
2012528632 Nov 2012 JP
2012528633 Nov 2012 JP
2012528634 Nov 2012 JP
2012528635 Nov 2012 JP
2012528636 Nov 2012 JP
2012528637 Nov 2012 JP
2012528638 Nov 2012 JP
2012528640 Nov 2012 JP
2012530576 Dec 2012 JP
2012532635 Dec 2012 JP
2012532636 Dec 2012 JP
2012532717 Dec 2012 JP
2012532720 Dec 2012 JP
2012532721 Dec 2012 JP
2012532722 Dec 2012 JP
5112330 Jan 2013 JP
5113847 Jan 2013 JP
101160735 Jul 2012 KR
20120091009 Aug 2012 KR
20120091153 Aug 2012 KR
20120091154 Aug 2012 KR
20120095919 Aug 2012 KR
20120099022 Sep 2012 KR
20120099101 Sep 2012 KR
20120102597 Sep 2012 KR
20120106754 Sep 2012 KR
20120106756 Sep 2012 KR
20120112503 Oct 2012 KR
2012006694 Jul 2012 MX
332622 Oct 2003 NO
572765 Aug 2012 NZ
587235 Aug 2012 NZ
00590352 Oct 2012 NZ
2023982 Nov 2012 PL
2274032 Oct 2012 PT
2346552 Nov 2012 PT
2462275 Mar 2011 RU
2459247 Aug 2012 RU
2011104496 Aug 2012 RU
2460546 Sep 2012 RU
2011109925 Oct 2012 RU
2011119019 Nov 2012 RU
181710 Jul 2012 SG
181790 Jul 2012 SG
184182 Oct 2012 SG
184328 Nov 2012 SG
184500 Nov 2012 SG
184501 Nov 2012 SG
184502 Nov 2012 SG
2274032 Dec 2012 SI
2346552 Dec 2012 SI
WO 8808724 Nov 1988 WO
WO 9113299 Sep 1991 WO
WO 9113430 Sep 1991 WO
WO 9219296 Nov 1992 WO
WO 9409839 May 1994 WO
WO 9411041 May 1994 WO
WO 9529720 Nov 1995 WO
WO 9529730 Nov 1995 WO
WO 9621482 Jul 1996 WO
9714455 Apr 1997 WO
WO 9714455 Apr 1997 WO
WO 9721457 Jun 1997 WO
WO 199741907 Nov 1997 WO
WO 9748430 Dec 1997 WO
WO 1998031369 Jul 1998 WO
WO 1998032451 Jul 1998 WO
WO 9831369 Jul 1998 WO
WO 9832451 Jul 1998 WO
WO 9903521 Jan 1999 WO
WO 9910030 Mar 1999 WO
WO 9922790 May 1999 WO
WO 9922789 May 1999 WO
WO 1999062525 Dec 1999 WO
WO 9962525 Dec 1999 WO
WO 0006228 Feb 2000 WO
WO 0024441 May 2000 WO
WO 0029050 May 2000 WO
WO 0193926 Dec 2001 WO
WO 02083216 Oct 2002 WO
WO 2002089805 Nov 2002 WO
WO 2089805 Nov 2002 WO
WO 3047663 Jun 2003 WO
WO 2003070296 Aug 2003 WO
WO 3068290 Aug 2003 WO
WO 03070296 Aug 2003 WO
WO 2003097133 Nov 2003 WO
WO 3097133 Nov 2003 WO
WO 2004028598 Apr 2004 WO
WO 2004041331 May 2004 WO
WO 2004047892 Jun 2004 WO
WO 2004108194 Dec 2004 WO
WO 2005002653 Jan 2005 WO
WO 2005005929 Jan 2005 WO
WO 2005009515 Feb 2005 WO
WO 2005053778 Jun 2005 WO
WO 2006079064 Jul 2006 WO
WO 2006086899 Aug 2006 WO
WO 2006125328 Nov 2006 WO
WO 2006130098 Dec 2006 WO
WO 2007047200 Apr 2007 WO
2007063342 Jun 2007 WO
WO 2007063342 Jun 2007 WO
WO 2007100899 Sep 2007 WO
2007131013 Nov 2007 WO
WO 2006079064 Nov 2007 WO
WO 2007129106 Nov 2007 WO
WO 2007131013 Nov 2007 WO
WO 2007131025 Nov 2007 WO
WO 2007143676 Dec 2007 WO
WO 2008005315 Jan 2008 WO
WO 2008009476 Jan 2008 WO
WO 2008058666 May 2008 WO
WO 2008089886 Jul 2008 WO
WO 2008100576 Aug 2008 WO
WO 2008107378 Sep 2008 WO
WO 2008112472 Sep 2008 WO
WO 2007104636 Dec 2008 WO
WO 2009049885 Apr 2009 WO
WO 2008071804 Aug 2009 WO
WO 2009114542 Sep 2009 WO
WO 2009132778 Nov 2009 WO
WO 2009141005 Nov 2009 WO
WO 2010003569 Jan 2010 WO
WO 2010043533 Apr 2010 WO
WO 2010046394 Apr 2010 WO
2010108116 Sep 2010 WO
WO 2010097116 Sep 2010 WO
WO 2010108116 Sep 2010 WO
WO 2011023736 Mar 2011 WO
WO 2011023882 Mar 2011 WO
WO 2011035877 Mar 2011 WO
WO 2011036133 Mar 2011 WO
WO 2011036134 Mar 2011 WO
WO 2011039163 Apr 2011 WO
WO 2011039201 Apr 2011 WO
WO 2011039202 Apr 2011 WO
WO 2011039207 Apr 2011 WO
WO 2011039208 Apr 2011 WO
WO 2011039209 Apr 2011 WO
WO 2011039211 Apr 2011 WO
WO 2011039216 Apr 2011 WO
WO 2011039217 Apr 2011 WO
WO 2011039218 Apr 2011 WO
WO 2011039219 Apr 2011 WO
WO 2011039228 Apr 2011 WO
WO 2011039231 Apr 2011 WO
WO 2011039232 Apr 2011 WO
WO 2011039233 Apr 2011 WO
WO 2011039236 Apr 2011 WO
WO 2011040861 Apr 2011 WO
WO 2011045385 Apr 2011 WO
WO 2011045386 Apr 2011 WO
WO 2011045611 Apr 2011 WO
WO 2011046756 Apr 2011 WO
WO 2011048223 Apr 2011 WO
WO 2011048422 Apr 2011 WO
WO 2011050359 Apr 2011 WO
2011060087 May 2011 WO
WO 2011053225 May 2011 WO
WO 2011054648 May 2011 WO
WO 2011054775 May 2011 WO
WO 2011056127 May 2011 WO
WO 2011067187 Jun 2011 WO
WO 2011067268 Jun 2011 WO
WO 2011067320 Jun 2011 WO
WO 2011067615 Jun 2011 WO
WO 2011068253 Jun 2011 WO
WO 2011069936 Jun 2011 WO
WO 2011073302 Jun 2011 WO
WO 2011073307 Jun 2011 WO
WO 2011076280 Jun 2011 WO
WO 2011080092 Jul 2011 WO
WO 2011081867 Jul 2011 WO
WO 2011081885 Jul 2011 WO
WO 2011089206 Jul 2011 WO
WO 2011089207 Jul 2011 WO
2011095478 Aug 2011 WO
2011095480 Aug 2011 WO
2011095483 Aug 2011 WO
2011095486 Aug 2011 WO
2011095488 Aug 2011 WO
2011095489 Aug 2011 WO
2011095503 Aug 2011 WO
2011101349 Aug 2011 WO
2011101376 Aug 2011 WO
2011101377 Aug 2011 WO
2011101378 Aug 2011 WO
2011101379 Aug 2011 WO
2011101380 Aug 2011 WO
2011101381 Aug 2011 WO
2011101382 Aug 2011 WO
2011101383 Aug 2011 WO
WO 2011099918 Aug 2011 WO
WO 2011101351 Aug 2011 WO
WO 2011101375 Aug 2011 WO
2011107805 Sep 2011 WO
2011109205 Sep 2011 WO
WO 2011110464 Sep 2011 WO
WO 2011110465 Sep 2011 WO
WO 2011110466 Sep 2011 WO
WO 2011111006 Sep 2011 WO
WO 2011112136 Sep 2011 WO
WO 2011113806 Sep 2011 WO
WO 2011117212 Sep 2011 WO
WO 2011117284 Sep 2011 WO
WO 2011117404 Sep 2011 WO
WO 2011121003 Oct 2011 WO
WO 2011121061 Oct 2011 WO
WO 2011123024 Oct 2011 WO
WO 2011124634 Oct 2011 WO
WO 2011126439 Oct 2011 WO
WO 2012020084 Feb 2012 WO
WO 2012022771 Feb 2012 WO
WO 2012090186 Jul 2012 WO
WO 2011042537 Aug 2012 WO
WO 2011042540 Aug 2012 WO
WO 2011043714 Aug 2012 WO
WO 2011051366 Sep 2012 WO
WO 2012122643 Sep 2012 WO
Non-Patent Literature Citations (48)
Entry
International Patent Application No. PCT/US14/23883, International Search Report dated Jul. 10, 2014 (3 pages).
International Patent Application No. PCT/US14/23485, International Search Report dated Jul. 7, 2014 (2 pages).
International Patent Application No. PCT/US14/24530, International Search Report dated Jul. 15, 2014 (2 pages).
International Patent Application No. PCT/US14/24543, International Search Report dated Jul. 28, 2014 (2 pages).
“Skin”, American Medical Association (AMA) Current Procedural Terminology , 1998, http://www.ama-assn.org/ama/pub/category/print/7176.html, 1 page.
Becks et al., “Comparison of Conventional Twice-Daily Subcutaneous Needle Injections to Multiple Jet Injections of Insulin in Insulin-Dependent Diabetes”, Clinical and Investigative Medicine, 1981, p. 33B.
Binder, “Absorption of Injected Insulin”, ACTA Pharmacological ET Toxicologica, 1969, 27(Supp 2), 3 pages.
Bonetti et al., “An Extended-Release formulation of Methotrexate for Subcutaneous Administration”, Cancer Chemotherapy Pharmacology, 1994, 33, 303-306.
Braun et al., “Comparison of the Clinical Efficacy and Safety of Subcutaneous Versus Oral Administration of Methotrexate in Patients with Active Rheumatoid Arthritis”, Arthritis and Rheumatism, Jan. 2008, 58(1), pp. 73-81.
Chen et al., “Blood Lipid Profiles and Peripheral Blood Mononuclear Cell Cholesterol Metabolism Gene Expression in Patients with and Without Methotrexate” BMC Medicine, 2011, 9(4), 9 pages.
Chiasson et al., “Continuous Subcutaneous Insulin Infusion (Mill-Hill Infuser) Versus Multiple Injections (Medi-Jector) in the Treatment of Insulin-Dependent Diabetes Mellitus and the Effects of Metabolic Control on Microangiopathy” Diabetes Care, Jul.-Aug. 1984, 7(4), pp. 331-337.
Cohn et al., “Clincal Experience with Jet Insulin Injection in Diabetes Mellitus Therapy: A Clue to the Pathogenesis of Lipodystrophy”, Ala. J. Med. Sci., 1974, 11(3), pp. 265-272.
Cowie et al., “Physical and Metabolic Characteristics of Persons with Diabetes”, National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, 1995, 95(1468), pp. 117-120.
European Patent Application No. 03707823.5, Supplementary European Search Report, dated Mar. 30, 2005 with Communication dated Apr. 25, 2005 regarding Proceeding Further with the European Patent Application Pursuant to Article 96(1), and Rule 51(1) EPC, 3 pages.
European Patent Application No. 00976612.2, Communication Pursuant to Article 96(2) EPC, dated May 10, 2004, 5 pages.
Hingson et al., “A Survey of the Development of Jet Injection in Parenteral Therapy”, Nov./Dec. 1952, 31 (6), pp. 361-366.
Hoekstra et al., Bioavailability of Higher Dose Methotrexate Comparing Oral and Subcutaneous Administration i n Patients with Rheumatoid Arthritis, The Journal of Rheumatology, 2004, 31(4), pp. 645-648.
International Patent Application No. PCT/US2012/46742, International Search Report and Written Opinion dated Nov. 16, 2012, 11 pages.
International Patent Application No. PCT/US2009/052835, International Search Report dated Mar. 15, 2010, 5 pages.
International Patent Application No. PCT/US2013/029085, International Search Report dated May 13, 2013, 2 pages.
International Patent Application No. PCT/US2010/028011, International Search Report, dated Jun. 29, 2010, 5 pages.
International Patent Application No. PCT/US2009/036682, International Search Report, dated Jul. 7, 2009, 5 pages.
International Patent Application No. PCT/US2007/068010, International Search Report, dated Sep. 24, 2007, 3 pages.
International Patent Application No. PCT/US03/03917, International Search Report, dated Nov. 26, 2003, 1 page.
Jansen et al., Methotrexaat Buiten de Kliniek, Pharmaceutisch Weekblad, Nov. 1999, 134(46), pp. 1592-1596.
Japanese Patent Application No. 2007-552367, Office Action dated Apr. 9, 2011.
Katoulis et al., Efficacy of a New Needleless Insulin Delivery System Monitoring of Blood Glucose Fluctuations and Free Insulin Levels, The International Journal of Artificial Organs, 1989, 12(5), 333-339.
Kurnik et al., “Bioavailability of Oral vs. Subcutaneous low-dose Methotrexate in Patients with Crohn's Disease”, Aliment Pharmacol Ther., Apr. 2003, 18, pp. 57-63.
Malone et al., “Comparison of Insulin Levels After Injection by Jet Stream and Disposable Insulin Syringe”, Diabetes Care, Nov.-Dec. 1986, 9(6), 637-640.
“The Historical Development of Jet Injection and Envisioned Uses in Mass Immunization and Mass Therapy Based Upon Two Decades' Experience”, Military Medicine, Jun. 1963, 128, pp. 516-524.
Pehling et al, “Comparison of Plasma Insulin Profiles After Subcutaneous Administration of Insulin by Jet Spray and Conventional Needle Injection in Patients with Insulin-Dependent Diabetes Mellitus”, Mayo Clin. Proc., Nov. 1984, 59, pp. 751-754.
Reiss et al., “Atheroprotective Effects of Methotrexate on Reverse Cholesterol Transport Proteins and Foam Cell Transformation in Human THP-1 Monocyte/Macrophages”, Arthritis and Rheumatism, Dec. 2008, 58(12), pp. 3675-3683.
Taylor et al., “Plasma Free Insulin Profiles After Administration of Insulin by Jet and Conventional Syringe Injection”, Diabetes Care, May-Jun. 1981, 4(3), 337-339.
Weller et al., “Jet Injection of Insulin vs the Syringe-and-Needle Method”, JAMA, Mar. 1966, 195(10), pp. 844-847.
Westlake et al., “The Effect of Methotrexate on Cardiovascular Disease in Patients with Rheumatoid Arthritis: A Systematic Literature Review”, Rheumatology, Nov. 2009, 49, pp. 295-307.
Worth, “Jet Injection of Insulin: Comparison with Conventional Injection by Syringe and Needle”, British Medical Journal, Sep. 1980, 281, pp. 713-714.
International Patent Application No. PCT/US2013/029085, Written Opinion, dated May 13, 2013, 5 pages.
International Patent Application No. PCT/US2010/028011, Written Opinion, dated Jun. 29, 2010, 5 pages.
Zachheim et al., “Subcutaneous Administration of Methotrexate”, Journal of the American Academy of Dermatology, 1992, 26(6), p. 1008.
Halle et al., “Twice-Daily Mixed Regular and NPH Insulin Injections with New Jet Injector Versus Conventional Syringes: Pharmacokinetics of Insulin Absorption”, Diabetes Care, May-Jun. 1986 9(3), pp. 279-282.
International Patent Application No. PCT/US2012/046639, International Search Report and Written Opinion dated Apr. 22, 2013, 8 pages.
Glynn-Barnhart et al., “Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy”, 1992, 12(5), abstract only, 2 pages.
Hamilton et al., “Why Intramuscular Methotrexate May be More Efficacious Than Oral Dosing in Patients with Rheumatoid Arthritis”, British Journal of Rheumatology, 1997, 36(1), pp. 86-90.
Stamp et al., “Effects of Changing from Oral to Subcutaneous Methotrexate on Red Blood Cell Methotrexate Polyglutamate Concentrations and Disease Activity in Patients with Rheumatoid Arthritis”, The Journal of Rheumatology, 2011, 38(12), 2540-2547.
Tukova et al., “Methotrexate Bioavailability after Oral and Subcutaneous Administration in Children with Juvenile Idiopathic Arthritis”, Clinical and Experimental Rheumatology, 2009, 27, 1047-1053.
Wright et al., “Stability of Methotrexate Injection in Prefilled Plastic Disposable Syringes”, International Journal of Pharmaceutics, Aug. 1988, 45(3), 237-244.
Lunenfeld, “Stable Testosterone Levels Achieved with Subcutaneous Testosterone Injections”, The aging Male, Mar. 2006, 9(1), 70 pages.
International Search Report dated Aug. 1, 2013 issued in connection with International Application No. PCT/US13/39976; International Filing Date: May 7, 2013.
Related Publications (1)
Number Date Country
20160263326 A1 Sep 2016 US
Provisional Applications (4)
Number Date Country
61776283 Mar 2013 US
61763395 Feb 2013 US
61643659 May 2012 US
61643845 May 2012 US
Continuations (1)
Number Date Country
Parent 13889183 May 2013 US
Child 15157851 US