Blood collection systems including an integral, flexible filter

Information

  • Patent Grant
  • 6745902
  • Patent Number
    6,745,902
  • Date Filed
    Friday, May 31, 2002
    22 years ago
  • Date Issued
    Tuesday, June 8, 2004
    20 years ago
Abstract
Blood collection systems include an integral flexible filter to remove leukocytes from blood components.
Description




FIELD OF THE INVENTION




The invention generally relates to blood collection and processing systems and methods.




BACKGROUND OF THE INVENTION




Systems composed of multiple, interconnected plastic bags have met widespread use and acceptance in the collection, processing and storage of blood components. Using these systems, whole blood is collected and separated into its clinical components (typically red blood cells, platelets, and plasma). The components are individually stored and used to treat a multiplicity of specific conditions and diseased states.




Before storing blood components for later transfusion, it is believed to be desirable to minimize the presence of impurities or other materials that may cause undesired side effects in the recipient. For example, because of possible reactions, it is generally considered desirable to remove substantially all the leukocytes from blood components before storage, or at least before transfusion.




Filtration is conventionally used to accomplish leuko-reduction. Systems and methods for reducing the number of leukocytes by filtration in multiple blood bag configurations are described, e.g., in Stewart U.S. Pat. No. 4,997,577, Stewart et al. U.S. Pat. No. 5,128,048, Johnson et al. U.S. Pat. No. 5,180,504, and Bellotti et. al. U.S. Pat. No. 5,527,472.




SUMMARY OF THE INVENTION




The invention provides a blood collection system comprising a container for holding blood and a filter communicating with the container. The filter includes first and second flexible sheets comprising a meltable material and a depth filter medium comprising a meltable material. A peripheral seal joins the sheets directly to the filter medium to encapsulate the filter medium between the first and second sheets. The seal comprises a commingled melted matrix comprising material of the sheets and material of the filter medium.




In a preferred embodiment, the filter medium removes leukocytes from blood.




Other features and advantages of the invention will become apparent upon review of the following description, drawings, and appended claims.











BRIEF DESCRIPTION OF THE DRAWINGS





FIG. 1

is a schematic view of a blood collection and storage system that includes an integral flexible filter that removes leukocytes from red blood cells;





FIG. 2

is an exploded perspective view of the integral flexible filter that forms a part of the system shown in

FIG. 1

, showing inlet and outlet ports that pass through the unitary peripheral seal;





FIG. 3

is an assembled perspective view of the integral flexible filter shown in

FIG. 2

;





FIG. 4

is an assembled perspective view of an alternative embodiment of an integral flexible filter that can form a part of the system shown in

FIG. 1

, showing inlet and outlet ports that do not pass through the unitary peripheral seal;





FIG. 5

is a perspective diagrammatic view showing a pre-assembled form of the integral flexible filter shown in

FIG. 2

, being assembled from continuous roll stock;





FIG. 6

is a side section view of the preassembled form of the integral flexible filter shown in

FIG. 5

, as it passes between two spaced apart radio frequency energy dies;





FIG. 7

is a side section view of the preassembled form of the integral flexible filter shown in

FIG. 6

, engaged by the dies, which apply radio frequency energy to form a unitary peripheral seal;





FIG. 8

is a top view of multiple sealed filter assemblies that are sequentially formed and die cut into individual filters


20


that can be integrated into the system shown in

FIG. 1

;





FIG. 9

is a schematic view of a blood collection and storage system that includes an integral flexible filter that removes leukocytes from red blood cells, with a by pass channel for venting air around the filter;





FIG. 10

is a schematic view of a blood collection and storage system that includes an integral flexible filter that removes leukocytes from red blood cells, with an integral air venting bag;





FIG. 11

is a schematic view of a blood collection and storage system that includes two integral flexible filters, one to remove leukocytes from red blood cells and the other to remove leukocytes from platelet-rich plasma; and





FIG. 12

is a schematic view of a blood collection and storage system that includes an integral flexible filter that removes leukocytes from whole blood prior to centrifugal processing.




The invention is not limited to the details of the construction and the arrangements of parts set forth in the following description or shown in the drawings. The invention can be practiced in other embodiments and in various other ways. The terminology and phrases are used for description and should not be regarded as limiting.











DESCRIPTION OF THE PREFERRED EMBODIMENTS





FIG. 1

shows a manual blood collection and storage system


10


having an integral flexible filter


20


. The system


10


provides red blood cells for long term storage that are substantially free of leukocytes. The system


10


also provides platelet concentrate and the platelet-poor plasma for long term storage. The blood collection and storage assembly


10


, once sterilized, constitutes a sterile, “closed” system, as judged by the applicable standards in the United States. The system


10


is a disposable, single use item.




As shown in

FIG. 1

, the system


10


includes a primary bag


12


and three transfer bags or containers


14


,


16


, and


18


. Like the flexible filter


20


, the transfer bags


14


,


16


, and


18


are integrally attached to the system


10


. In use, the system


10


is manipulated in conventional ways. The primary bag


12


(which is also called a donor bag) receives whole blood from a donor through integrally attached donor tube


22


that carries an phlebotomy needle


24


. A suitable anticoagulant A is contained in the primary bag


12


. The whole blood is centrifugally separated by convention means inside the primary bag


12


into red blood cells and platelet-rich plasma. Leukocytes dwell in the interface between the red blood cells and platelet-rich plasma.




The transfer bag


14


is intended to receive platelet-rich plasma separated from the whole blood collected in the primary bag


12


. Attempts are made when transferring the platelet-rich plasma out of the primary bag


12


to keep as many leukocytes in the primary bag


12


as possible. The transfer of platelet-rich plasma into the transfer bag


14


leaves the red blood cells and the leukocytes behind in the primary bag


12


.




The transfer bag


16


contains a suitable storage solution S for red blood cells. One such solution is disclosed in Grode et al U.S. Pat. No. 4,267,269, which is sold by Baxter Healthcare Corporation under the brand name ADSOL® Solution. The storage solution S is transferred into the primary bag


12


after transfer of the platelet-rich plasma into the transfer bag


14


.




The platelet-rich plasma is centrifugally separated by conventional means in the transfer bag


14


into platelet concentrate and platelet-poor plasma. The platelet-poor plasma is transferred into the transfer bag


16


, which is now emptied of storage solution S. The transfer bag


16


serves as the storage container for the platelet-poor plasma. The transfer bag


14


serves as its storage container for the platelet concentrate.




The storage solution S is mixed with the red blood cells and leukocytes remaining in the primary bag


12


. The mixture of storage solution S, red blood cells, and leukocytes is transferred from the primary bag


12


through tubing


26


. The tubing


26


carries in-line the integral, flexible filter


20


. The flexible filter


20


includes a filtration medium


28


contained within a housing


30


. The filtration medium is selected to remove leukocytes from red blood cells.




The leukocyte-reduced red blood cells enter the transfer bag


18


. The transfer bag


18


serves as the storage container for the leukocyte-reduced red blood cells.




The bags and tubing associated with the processing system


10


can all be made from conventional approved medical grade plastic materials, such as polyvinyl chloride plasticized with di-2-ethylhexyl-phthalate (PVC-DEHP). The bags are formed using conventional heat sealing technologies, e.g., radio frequency (RF) heat sealing.




Alternatively, since the transfer bag


14


is intended to store the platelet concentrate, it can be made of polyolefin material (as disclosed in Gajewski et al U.S. Pat. No. 4,140,162) or a polyvinyl chloride material plasticized with tri-2-ethylhexyl trimellitate (TEHTM). These materials, when compared to DEHP-plasticized polyvinyl chloride materials, have greater gas permeability that is beneficial for platelet storage.




The flexible filter


20


, like the rest of the system


10


, is a disposable, single use item. Also, like the rest of the system


10


, the filter housing


30


is made using conventional approved medical grade plastic materials. Furthermore, like the rest of the system


10


, the filter housing


30


is formed using conventional radio frequency heat sealing technology. The filter


20


, being flexible, facilitates handling and reduces the incidence of damage to other components of the system


10


during centrifugal processing.




In the illustrated embodiment (see FIG.


2


), the filter housing


30


comprising first and second sheets


32


and


34


of medical grade plastic material, such as polyvinyl chloride plasticized with di-2-ethylhexyl-phthalate (PVC-DEHP). Other medical grade plastic materials can be used that are not PVC and/or are DEHP-free, provided that the material heats and flows when exposed to radio frequency energy.




The filtration medium


28


is made from a fibrous material, which is sandwiched between the sheets


32


and


34


. The filtration medium


28


can be arranged in a single layer or in a multiple layer stack. The medium


28


can include melt blown or spun bonded synthetic fibers (e.g., nylon or polyester or polypropylene), semi-synthetic fibers, regenerated fibers, or inorganic fibers. In use, the medium


28


removes leukocytes by depth filtration.




In the illustrated embodiment, the filtration medium


28


comprises, in the blood flow direction, a prefilter region, a main filter region, and a postfilter region. The prefilter and postfilter are made of fibrous material (e.g., polyethylene) having a pore size and fiber diameter not suited for leukocyte removal. Instead, the fibrous material of the prefilter is sized to remove gross clots and aggregations present in the blood. The fibrous material of the postfilter is sized to provide a fluid manifold effect at the outlet of the filter. In a representative embodiment, the prefilter material has a pore size of between about 15 μm to about 20 μm, and the postfilter material has a pore size of about 20 μm. The main filter region is made of a fibrous material (e.g., polyethylene) having a pore size and diameter sized to remove leukocytes by depth filtration. The material of the main filter region can have the characteristics described in Watanabe et al. U.S. Pat. No. 4,701,267 or Nishimura et al. U.S. Pat. No. 4,936,998, which are incorporated herein by reference.




As disclosed, the filtration medium


28


can be made symmetric, meaning that the material layers of filtration medium encountered during flow through the medium


28


are the same regardless of the direction of flow. Thus, either side of the medium


28


can serve as an inlet or an outlet. The symmetric nature of the filtration medium


28


further simplifies manufacture, as it is not necessary to differentiate between “inlet” and “outlet” side of the filtration medium


28


or “inlet” or “outlet” orientation of the sheets


32


and


34


.




According to the invention, a unitary, continuous peripheral seal


36


is formed by the application of pressure and radio frequency heating in a single process to the two sheets


32


and


34


and filtration medium


28


. The seal


36


joins the two sheets


32


and


34


to each other, as well as joins the filtration medium


28


to the two sheets


32


and


34


. The seal


36


integrates the material of the filtration medium


28


and the material of the plastic sheets


32


and


34


, for a reliable, robust, leak-proof boundary. Since the seal


36


is unitary and continuous, the possibility of blood shunting around the periphery of the filtration medium


30


is eliminated.




The filter


20


also includes inlet and outlet ports


38


and


40


. The ports


38


and


40


comprise tubes made of medical grade plastic material, like PVC-DEHP. As

FIG. 3

shows, the ports


38


and


40


can be located in the integrated peripheral seal


36


, and be sealed in place at the same time that the unitary peripheral seal


36


is formed. Alternatively (see FIG.


4


), the ports


38


and


40


can be inserted and sealed to each sheet


32


and


34


in a separate assembly process before the unitary peripheral seal is formed, in the manner shown in Fischer et al. U.S. Pat. No. 5,507,904. Still alternatively, the ports


38


and


40


can comprise separately molded parts that are heat sealed by radio frequency energy over a hole formed in the sheets.




The symmetric orientation of filtration medium


28


, described above, makes the filter


30


“non-directional.” The port


38


can be oriented to serve either as an inlet port or an outlet port, with the other port


40


serving, respectively, as the corresponding outlet port or inlet port, and vice versa.




The filter


20


(see

FIG. 5

) is formed from roll stock


42


and


44


of the first and second plastic sheets


32


. The layer or layers of filtration medium


28


are also supplied from roll stock


46


. The roll stock


42


,


44


, and


46


supply a continuous, layered filter pre-assembly


48


. The pre-assembly


48


is advanced in measured steps between a pair of opposed dies


50


and


52


(see FIG.


6


). Between each step, the opposed dies


50


and


52


are moved together (see FIG.


7


), to apply pressure to press the peripheral edge of the pre-assembly


48


together. Preferably a stop


54


is provided to accurately space the dies


50


and


52


apart from each other.




As the dies


50


and


52


apply pressure about the peripheral edge, RF energy is applied through the dies


50


and


52


, The combination of RF energy and pressure softens the plastic material of the sheets


32


and


34


. The applied pressure causes the heat softened material of the sheets


32


,


34


to penetrate the interstices of the filtration medium


28


, creating an interior matrix of sheet material commingled with filtration medium material. Within the matrix, the filtration medium melts, creating a composite seal


36


.




At its surface, along the sheets


32


and


34


, the seal


36


comprises mostly the material of the sheets


32


and


34


. With increasing distance from the surface, the seal


36


comprises a commingled melted matrix of the material of the sheets


32


and


34


and the material of the filtration medium


28


. This is believed to occur because the sheet material, which is electrically heated and caused to flow by the applied radio frequency energy, is further caused by the applied pressure to flow into and penetrate the interstices of the medium


28


. The heated sheet material that flows under pressure into the interstices of the medium


28


causes the medium


28


itself to melt about it.




After a brief period of cooling, the seal


36


sets and the dies


50


and


52


are withdrawn. In a representative embodiment, the dies


50


and


52


are coupled to a 4 KW radio frequency energy generator. Pressure of 60 PSI is applied, maintaining a die gap of 1.2 mm. A sealing time of about 5.5 seconds is realized, followed by a cooling time of about 5 seconds.




As

FIG. 8

shows, multiple sealed filter assemblies


56


can be sequentially formed along the pre-assembly


48


. The filter assemblies are die cut into individual filters


20


(as shown by phantom lines


84


in FIG.


8


). The filter


20


is then integrated into a blood processing and collection system


10


, as shown in FIG.


1


.




As

FIGS. 6 and 7

show, when the port tubes


38


and


40


are to be located within the peripheral seal


36


, the dies


50


and


52


can be provided with aligned concave recesses


58


. The recesses


58


register to receive the port tubes


38


and


40


. The dies


50


and


52


are brought together about the port tubes


38


and


40


and along the remaining periphery of the pre-assembly


48


. Mandrels (not shown) are inserted into the tubes


38


and


40


to prevent deformation of the tubes


38


and


40


while the seal


36


forms. The mandrels are removed after the seal


36


cools.




Once integrated into the system


10


, the flexible filter housing


30


comprises a variable volume reservoir that can be used, after filtration, to receive residual air trapped in the transfer bag


18


. In this arrangement, after leukocyte-depleted red blood cells have been transferred from the filter


20


into the bag


18


, residual air is expressed from the transfer bag


18


back into the filter housing


30


. Tubing upstream of the filter


20


can be clamped closed to trap air in the filter housing


30


. Being flexible, the housing


30


expands to accommodate the residual air volume.




Alternatively, the residual air in the transfer bag


18


can be transferred back into the primary bag


12


through an air vent path that bypasses the filter


20


. For example, as

FIG. 1

shows, a tubing path


60


leads from the transfer bag


18


to the primary bag


12


, through which residual air can be vented out of the transfer bag


18


.




Instead of the tubing path


60


(see FIG.


9


), an air bypass channel


62


can be provided around the filter


20


. An in-line one-way valve


64


can be placed in the bypass channel


62


, to prevent blood flow through the channel in the direction toward the transfer bag


18


. In another alternative arrangement (see FIG.


10


), residual air in the transfer bag


18


can be transferred into an air vent bag


66


through an integral air vent tube


68


.




A flexible filter can be integrated in different ways into multiple blood bag systems. For example (see FIG.


11


), a system


10


′ like that shown in

FIG. 1

can include a second integral flexible filter


20


′ in-line between the primary bag


12


and the transfer bag


14


. In this arrangement, the filtration medium


28


′ is selected to remove leukocytes from platelet-poor plasma prior to entering the transfer bag


14


.




As another example,

FIG. 12

shows a system


70


that includes a primary bag


72


and transfer bags


74


,


76


,


78


. The primary bag


72


receives whole blood from a donor. The whole blood is transferred from the primary bag


72


through tubing


80


into the transfer bag


74


. The tubing


80


carries in-line an integral, flexible filter


82


of the type previously described. The filtration medium


84


is selected to remove leukocytes from the whole blood, without also removing platelets or red blood cells. The leukocyte-depleted whole blood is centrifugally processed in the transfer bag


74


into red blood cells and platelet-rich plasma, both of which are in a leukocyte-depleted condition.




The transfer bag


76


receives the leukocyte-depleted platelet-rich plasma, leaving the leukocyte-depleted red blood cells in the transfer bag


74


for storage. The platelet-rich plasma is centrifugally separated by conventional means in the transfer bag


76


into platelet concentrate and platelet-poor plasma. The platelet-poor plasma is transferred into the transfer bag


78


for storage. This leaves the platelet concentrate in the transfer bag


76


, which serves as its storage container.




The flexible filter that embodies the invention avoids the handling and processing problems rigid filter housings have presented in the past. Unlike a rigid housing, the flexible housing


30


will not puncture associated bags, which are also made of flexible plastic materials. Unlike a rigid housing, the flexible housing


30


conforms and is compliant to stress and pressures induced during use.




The close proximity of the flexible sheet


32


and the filtration medium


28


on the inlet side of the filter


20


creates a capillary effect, which promotes displacement of air and automatic priming of the filter


30


under the fluid head pressure of gravity flow from a source container. The fluid head pressure causes the flexible sheet


32


to distend or expand after priming. It thus creates a natural pressure manifold, which evenly distributes the fluid across the inlet face of the filtration medium


28


. This assures that entrapped air is vented and that the fluid flows through the filtration medium


28


under uniform pressure and distribution.




As the fluid container empties, negative pressure is created downstream of the filter


20


. Because the inlet and outlet sheets


32


and


34


of the housing


30


are flexible, they will collapse around the space occupied by the filtration medium


28


, minimizing the amount of residual blood left in the filter


30


after use. Fluid drains from the outlet side without the use of an auxiliary air vent.




By the same process, the flexible filter


30


provides a visual indication of an upstream occlusion or blockage during use. If an occlusion occurs in the inlet tubing upstream of the filter


30


during use (e.g., by formation of a kink in the tubing or by formation of an in-line blood clot), the inlet and outlet sheets


32


and


34


of the housing


30


will respond by collapsing, in the same fashion occasioned by an empty source container. Thus, an unexpected collapse of the filter


30


during use visually signifies the presence of an occlusion upstream of the filter


30


.




Furthermore, the flexible housing


30


will not crack during heat sterilization. The flexible housing


30


also does not impede heat penetration during heat sterilization processes. Instead, the housing


30


accommodates uniform heat penetration into the filtration medium


28


. The filter


20


can undergo sterilization at the same time the entire system


10


is sterilized, making a one-step sterilization process possible.




Various features of the invention are set forth in the following claims.



Claims
  • 1. A blood filter device comprisingfirst and second flexible sheets, each sheet comprising a meltable material, a filter medium comprising a prefilter layer, a main filter layer, and a postfilter layer, each layer comprising a meltable material, a peripheral seal formed by application of radio frequency heating and pressure in a single step to join the first and second flexible sheets directly to the filter medium and encapsulate the filter medium between the first and second flexible sheets, with the first flexible sheet overlying the prefilter layer, the second flexible sheet overlying the postfilter layer, and the main filter layer sandwiched between the prefilter and postfilter layers, the peripheral seal comprising a commingled melted matrix comprising material of the sheets and material of the filter medium, an inlet port located in the first flexible sheet spaced from the peripheral seal for conveying blood to the filter medium, and an outlet port located in the second flexible sheet spaced from the peripheral seal for conveying blood from the filter medium.
  • 2. A blood filter device according to claim 1wherein the meltable material of the main filter layer serves to remove leukocytes from blood by depth filtration.
  • 3. A blood filter device according to claim 1wherein the meltable material of the prefilter layer serves to remove aggregations present in blood.
  • 4. A blood collection system comprisinga container for holding blood, a blood filter device as defined in claim 1 or 2 or 3, and tubing connecting the blood filter device to the container.
  • 5. A blood filter assembly comprising a plurality of blood filter devices, each as defined in claim 1, arranged in series in an adjacent side-by-side relationship.
RELATED APPLICATIONS

This application is a division of application Ser. No. 09/593,782 filed Jun. 14, 2000 (now U.S. Pat. No. 6,422,397), which is a continuation-in-part of application Ser. No. 09/498,085 filed Feb. 4, 2000 (now U.S. Pat. No. 6,367,634), which application is also a continuation-in-part of U.S. patent application, Ser. No. 08/697,270, filed Aug. 21, 1996 (now U.S. Pat. No. 6,032,807), which is a continuation of U.S. patent application Ser. No. 08/558,458, filed Nov. 16, 1995 (now abandoned), which is a continuation of U.S. patent application Ser. No. 08/392,297, filed Feb. 22, 1995 (now abandoned), which is a continuation of U.S. patent application Ser. No. 08/173,608, filed Dec. 22, 1993 (now abandoned).

US Referenced Citations (72)
Number Name Date Kind
3506130 Shaye Apr 1970 A
3747769 Brumfield Jul 1973 A
4025618 Garber et al. May 1977 A
4035304 Watanabe Jul 1977 A
4066556 Vaillancourt Jan 1978 A
4113627 Leason Sep 1978 A
4157967 Meyst et al. Jun 1979 A
4170056 Meyst et al. Oct 1979 A
4193876 Leeke et al. Mar 1980 A
4211825 Shipman Jul 1980 A
4234026 Bayham Nov 1980 A
4235233 Mouwen Nov 1980 A
4240481 Bayham Dec 1980 A
4268338 Peterson May 1981 A
4305443 Bayham Dec 1981 A
4380484 Repik et al. Apr 1983 A
4417753 Bacehowski et al. Nov 1983 A
4425177 Shinno Jan 1984 A
4437472 Naftulin Mar 1984 A
4460366 Shinno Jul 1984 A
4466888 Verkaart Aug 1984 A
4482585 Ohodaira et al. Nov 1984 A
4493705 Gordon et al. Jan 1985 A
4507123 Yoshida Mar 1985 A
4539793 Malek Sep 1985 A
4707402 Thorsrud Nov 1987 A
4767541 Wisdom Aug 1988 A
4770295 Carveth et al. Sep 1988 A
4798578 Ranford Jan 1989 A
4857129 Jensen et al. Aug 1989 A
4863603 Lehmann et al. Sep 1989 A
4892603 Lustig et al. Jan 1990 A
4892604 Measells et al. Jan 1990 A
4894107 Tse et al. Jan 1990 A
4900389 Schnell et al. Feb 1990 A
4900441 Graus et al. Feb 1990 A
4950347 Futagawa Aug 1990 A
4954251 Barnes et al. Sep 1990 A
4976851 Tanokura et al. Dec 1990 A
4997577 Stewart Mar 1991 A
5049146 Bringham et al. Sep 1991 A
5055198 Shettigar Oct 1991 A
5066290 Measells et al. Nov 1991 A
5180504 Johnson et al. Jan 1993 A
5190657 Heagle et al. Mar 1993 A
5225014 Ogata et al. Jul 1993 A
5269924 Rochat Dec 1993 A
5306269 Lewis et al. Apr 1994 A
5316678 Heaslip May 1994 A
5360498 Blomqvist et al. Nov 1994 A
5420962 Bakke May 1995 A
5435878 Delmar et al. Jul 1995 A
5449428 Desmarais et al. Sep 1995 A
5489385 Raabe et al. Feb 1996 A
5507904 Fisher et al. Apr 1996 A
5527472 Bellotti et al. Jun 1996 A
5556541 Ruschke Sep 1996 A
5575880 Strassberg Nov 1996 A
5580349 Thor et al. Dec 1996 A
5583577 Tsukagoshi Dec 1996 A
5591337 Lynn et al. Jan 1997 A
5601730 Page et al. Feb 1997 A
5683768 Shang et al. Nov 1997 A
5688460 Ruschke Nov 1997 A
5724988 Dennehey et al. Mar 1998 A
5728249 Kinsey, Jr. et al. Mar 1998 A
5728306 Breillatt, Jr. et al. Mar 1998 A
5736719 Lawson et al. Apr 1998 A
5772880 Lynn et al. Jun 1998 A
5858016 Bacehowski et al. Jan 1999 A
5976300 Buchanan et al. Nov 1999 A
6032807 Sternberg et al. Mar 2000 A
Foreign Referenced Citations (15)
Number Date Country
0155003 Sep 1985 EP
0328038 Aug 1989 EP
0365676 May 1990 EP
0 365 676 May 1990 EP
0 516 846 Dec 1992 EP
0 521 222 Jan 1993 EP
0 525 493 Feb 1993 EP
0526678 Feb 1993 EP
0526678 Feb 1993 EP
0614675 Sep 1994 EP
0 654 303 May 1995 EP
0679490 Nov 1995 EP
684867 Dec 1995 EP
WO9507818 Mar 1995 WO
WO9517237 Jun 1995 WO
Non-Patent Literature Citations (2)
Entry
Excerpts from Opposition involving EP 684,867 (European Counterpart of Lynn US 5,591,337) including (1) Notice of Opposition; (2) Response to Opposition; (3) Statement Replying to Response; (4) Reply to Statement in Response; and (5) Opposition Decision.
Opposition Decision, European Patent Office, May 15, 2001; Ref. No. BAXR/M7328EP EP 684867.
Continuations (3)
Number Date Country
Parent 08/558458 Nov 1995 US
Child 08/697270 US
Parent 08/392297 Feb 1995 US
Child 08/558458 US
Parent 08/173608 Dec 1993 US
Child 08/392297 US
Continuation in Parts (2)
Number Date Country
Parent 09/498085 Feb 2000 US
Child 09/593782 US
Parent 08/697270 Aug 1996 US
Child 09/498085 US