In previous patent applications, U.S. patent application Ser. No. 12/097,204 (now abandoned), and PCT/FR2007/001042, filed Jun. 22, 2007, each of which expressly incorporated herein by reference in their entirety, the present applicant has described a new method for detecting some low electromagnetic frequency electromagnetic signals in diluted filtrates of the culture medium of certain bacteria and viruses, as well as in diluted plasma of patients infected by the same agents. The electromagnetic signals (EMS) were believed to be produced by certain defined nanostructures induced by the microorganisms, in high dilutions of in water, the nanostructures being previously removed by filtration.
See (each of which is expressly incorporated herein by reference):
See also, U.S. Pat. Nos. 7,412,340, 7,081,747, 6,995,558, and 6,952,652, each of which is expressly incorporated herein by reference.
The present invention concerns the identification of the molecules present in, for example, bacteria which are the sources of the signals. In particular, some particular forms and sequences of DNA from potentially pathogenic bacteria may give rise to these signals. The extraction of DNA has the advantage of facilitating the detection of electromagnetic signals from complex biological fluids, even when they have been kept frozen at low temperature. The method is particularly appropriate for the detection, identification and treatment of chronic bacterial infections in diseases associated with autoimmune components, such as rheumatoid arthritis and multiple sclerosis, or in neuropathies of unknown origin such as Alzheimer's and Parkinson's diseases.
In preliminary experiments, the inventor had observed that a pretreatment of a suspension of Escherichia coli (E. Coli) by 1% formaldehyde did not alter its capacity to induce the electromagnetic signals, while killing the bacteria. This treatment alters the surface proteins of the bacterial cells without attacking their genetic material, i.e., double-helical DNA. This suggested that the source of the signals may be the DNA itself. Indeed, DNA extracted from the bacterial suspension by the classical phenol:chloroform extraction technique was able, upon filtration and appropriate dilutions in water, to emit electromagnetic signals similar to those produced by intact bacteria under the same conditions. DNAse treatment of the extracted DNA solution abolishes the capacity to emit signals, provided one eliminates the source of signal coming from the nanostructures previously induced by the DNA.
It is therefore an object of the invention to provide a method for detecting electromagnetic waves derived from bacterial DNA, comprising extracting and purifying nucleic acids from a sample; diluting the extracted purified nucleic acids in an aqueous solvent; measuring a low frequency electromagnetic emission over time from the diluted extracted purified nucleic acids in an aqueous solvent; performing a signal analysis of the low frequency electromagnetic emission over time; and producing an output, based on the signal analysis, in dependence on the DNA in the sample. The output may vary in dependence on DNA in the sample derived from pathogenic bacteria in plasma of patients suffering from chronic diseases. The sample may contain DNA extracted from at least one of blood or blood plasma, feces, urine, saliva, tears, seminal fluid, sweat, seminal and vaginal fluids of a patient. The sample may also contain DNA extracted from potable water. For example, the sample may contain DNA which is extracted from samples previously frozen and stored at temperatures between about −20° C. and −70° C. The diluting step may, for example, dilute the DNA by about 10−7 to 10−13.
The extracting and purifying process may comprise: diluting the sample with an aqueous buffer and mixing; degrading proteins in the diluted sample; precipitating DNA from the buffer solution; and resuspending the precipitated DNA in an aqueous solution. Further, the resuspended DNA may be filtered through at least one submicron filter, wherein the sample measured comprises the filtrate. The filtrate may be diluted in an aqueous solution prior to measuring. The resuspended DNA may be diluted by 102 to 1020 prior to measurement.
The measuring may comprise placing the diluted extracted purified nucleic acids near an antenna adapted to receive electromagnetic signals having a frequency approaching about 0 Hz and up to 20 kHz, and receiving the electromagnetic signals from the antenna.
The signal analysis may comprise performing a time domain to frequency domain transformation on the signal. Transformed signals from two different samples may be compared. For example, the transform may be a frequency domain (such as an FFT or DFT, generally using an appropriate window function), wavelet domain, or other reversible or irreversible transform. The signal analysis may comprise applying a threshold function to the frequency domain transformed signal. The threshold function may be a static or dynamic or adaptive threshold, and may be uniform or changing over a spectrum of characteristics. The signal analysis may comprise a three-dimensional histogram. The signal analysis may comprise reducing a background noise component of the signal. The signal analysis may comprise selective analysis of signal components having frequencies between about 500-3000 Hz.
The signal analysis may be performed on a general purpose computer, for example having a processor, memory for storing program instructions and data, an operating system, application software, and inputs and outputs, and the output may be presented through a graphic user interface.
A typical experiment is described as follows: First, extreme precautions have to be taken at all steps of the process in order to avoid adventitious contamination from external sources: all manipulations have to be done in a class 100 or better laminar flow hood, and centrifugations are operated in stoppered sterile tubes. The water used for dilutions of reagents and samples has been obtained by distillation at 500° C. (pyrolysis) to destroy any macromolecular organic compound.
1) DNA Extraction:
The sample is first equilibrated at room temperature (15-20° C.), then it is diluted 1:100 in a volume of 400 μl final in sterile PBS 1× in a 2 ml microcentrifuge tube, and mixed by pulse-vortexing for 10 sec.
40 μl of a 10 mg/ml solution of Proteinase K are added (1 mg/ml final concentration) and then 20 μl of an aqueous solution of SDS 10% (Sodium Dodecyl Sulfate) are added (0.5% final concentration). The mixture is mixed by pulse-vortexing for 10 sec, and incubated 15 min at 56° C.
500 μl of Phenol:Chloroform:IsoAmyl Alcohol (25:24:1), are then added and mixed by pulse-vortexing for 20 sec. The mixture is centrifuged for 10 min at room temperature at 6000×9 (8000 rpm). The upper aqueous phase is collected (approximately 500 μl) and placed in a new 2 ml microcentrifuge tube. Cold ethanol, 2.5 volumes (1,125 μl) and 2.5M Sodium Acetate (pH 5.2), 1:10 of final volume (160 μl) are added to precipitate the DNA, mixed by inverting the tube carefully (5-10 times) and left for 15 min at 20° C. The sample is centrifuged for 30 min at 14,000 rpm at 4° C. and the supernatant is discarded. The pellet is washed twice by 500 μl of cold ethanol 70% and the suspension is centrifuged for 10 min at 14,000 rpm at 4° C. The supernatant is discarded and the pellet is dried at room temperature for 15 min. The pellet is then re-suspended in 60 μl Tris 10 mM (pH 7.6), mixed by pipetting and stored at 4° C. for immediate use in the SEM protocol or frozen at −20° C. or preferentially at −70° C. for further analysis.
2) EMS Measurement:
An aliquot of the DNA solution is diluted 1:100 vol/vol in water and the dilution is filtered first through a Millipore filter of pore size 0.45 μm (Millex). The filtrate is filtered again through a 0.1 μm Millipore filter. This filtration step is important, and it has been observed that no signals are detected in its absence at any dilution. In contrast to the microorganism suspensions where the filtration was supposed to retain the bacteria or viruses, this filtration let the DNA pass through, and the latter is therefore still present in the filtrate.
By definition, the “filtrate” is the liquid which has passed through the pores of the filter and is not retained by the filter.
The role of filtration for the DNA solution is probably to dissociate the network of nanostructures which are trapped in a gel at high concentration, thus allowing them to vibrate in resonance with the excitation produced by the electromagnetic background.
The filtration step must be immediately followed by the dilution steps 10 by 10 in water as previously described, for the filtrates of plasma or of microorganism suspensions.
For each dilution, 0.1 ml of the previous dilution is added to 0.9 ml of water in an Eppendorf conical tube, and strongly agitated for 15 seconds in a vortex mixer. Again, 0.1 ml of this solution is diluted in 0.9 ml of water, etc.
Usually, the range of dilutions is made between 10−2 and 10−15, eventually 10−20. Capture and analysis of the EMS is proceeded as previously described in U.S. patent application Ser. No. 12/097,204, and as shown in
The detection of signals is performed with equipment shown in a schematic view in
An amplitude raw global representation is presented. Some background noise is generally present, which can then be filtered. A positive signal is detected when the amplitude exceeds at least 1.5 times the background noise. In general, the detected amplitude is twice and sometimes three times, the background noise. This detected signal is called an SEM electromagnetic signal.
A 3D histogram analysis may be performed, respectively of the background noise and the signal in presence of the sample. The recorded signal may be broken down into individual frequencies through a Fourier transform of the background noise and the signal respectively in the presence of the sample. Of course, other types of signal analysis may be employed, for example wavelet analysis, principal component analysis, or other linear, non-linear, statistical, discrete, etc. analysis techniques which analyze a signal amplitude with respect to time signals, particularly those which extract or emphasize information represented therein.
Each dilution tube is placed on the top of a solenoid transforming changes in the magnetic field into an electric current. The current is amplified 500 times by a SoundBlaster® card and analyzed on a computer employing three software applications: one for direct recording of the waves, and two for performing Fourier analysis of the harmonics, as shown in
A positive signal is generally defined by an increase of higher frequencies (500-3,000 Hz) over the respective background sample, though the criteria may be different for different types of analysis; that is, using a Fourier analysis, the positive experimental show a significant difference from control with respect to an increase in signal energy in the 500-3,000 Hz band. Using other analysis techniques, the definition of a positive result will correspondingly be different.
Usually positive signals are found in the range of the 10−7 to 10−13 dilutions. At high dilutions (from 10−12), calculations indicate that there is no DNA left and that the EMS should come for self-maintained nanostructures induced in water by the DNA from which they originated.
3) Effect of DNAse:
Destruction of DNA sequences by DNAse abolishes their capacity to induce EMS in water. Since the nanostructures formed in water are fully resistant to DNAse, but are sensitive to heat, the DNAse effect is shown according to the following protocol, designed to suppress this secondary source of EMS. The DNA preparation is heated at 100° C. for 30 min to destroy the nanostructures. After cooling at 37° C., DNAse I at a final concentration of 10 U/μg of DNA is added to the DNA solution and incubated in the presence of 5 mM MgCl2 for 16 Hours at 37° C. An aliquot of untreated DNA solution is kept as a positive control. The DNAse treated preparation is completely devoid of EMS emission at any dilutions. Therefore the main source of EMS is DNA.
4) Nature of the DNA sequences at the origin of EMS:
A survey of the main bacteria species involved in human infections indicated that the following species are producing signals, either as pure culture suspension, or as DNA:
Escherichia coli (strain K1)
Streptococcus B
Staphylococcus aureus
Proteus mirabilis
Pseudomonas aeruginosa
Bacillus aeruginosa
Mycoplasma pirum
Positive dilutions were all in the range of 10−7 to 10−13 and the signal frequency profiles were similar, although small differences may exist between species and may be revealed by a more refined signal analysis. By contrast, no signals were detected from certain strains of E. Coli used as plasmid vector for molecular cloning such as E. coli XL1 B (Stratagene) and E. coli TOP10 (Invitrogen) and also in bacteria known to be apathogenic, such as Lactobacillus and Bacillus Calmette-Guerin. This indicated that only some specific sequences of bacterial DNA were at the origin of EMS. As shown in
This data suggests that a simplified analysis of spectral energy at about 1,500 Hz or more generally in the 1,400-2,000 Hz band may be sufficient to determine the presence of the effect, and therefore than a relatively simple instrument, without requiring complex analytical software, may be used for screening samples.
In an attempt to analyze the nature of the sequences involved, Mycoplasma pirum species was used, in which a gene indispensable for its eventual pathogenic role was cloned, the gene coding for the adhesin protein, a protein necessary for the attachment of the bacterium to eukaryotic cells.
This gene was cloned in a plasmid carried by an E. Coli strain in two fragments corresponding respectively to the N-terminus and the C-terminus of the protein.
The vector E. Coli strain (XL1 B) lacking the plasmid did not produce EMS as well as its extracted DNA.
By contrast, when the bacterial strain was transformed by the plasmids carrying the adhesin gene fragments, its extracted DNA produced EMS as well as the purified plasmid DNA.
The two gene fragments were excised by appropriate restriction enzymes from the plasmid and purified by electrophoresis in agarose gel. The electrophoretic bands corresponding to their molecular weight (respectively 1.5 Kb for the N-terminus and 3.5 Kb for C-terminus) were cut from the gel and the DNA fragments were eluted.
Again, upon the procedure previously described (filtration with 0.45 μm and 0.1 μm filters) the two pure DNA fragments corresponding to the adhesin gene each yielded typical EMS.
This result indicates that the present method is able to distinguish in a given bacterium between the specific DNA sequences which are responsible for emitting the electromagnetic signals.
The adhesin gene of M. pirum is, in its native state, part of the chromosomal DNA, indicating that whatever be its location, plasmidic or integrated, its sequences by themselves are able to induce EMS.
This procedure opens the way to a more refined intragenic analysis of the minimal sequences of a gene which are responsible for the EMS.
It is noted that, while the signals themselves may be similar for various DNA samples which are associated with the EMS, the DNA sequences themselves are different. Therefore, the DNA sequence giving rise to a signal may be inferred based on similarities of the EMS to the corresponding EMS of authentic samples (either gathered contemporaneously or retrieved from a database), and/or by studies which target particular DNA sequences, and thereby modify signals associated with those sequences. For example, the EMS associated with DNA may be modified by small molecule agents, binding proteins and factors, DNA (e.g., primer-type sequences) or RNA (e.g., siRNA) or other nucleic acid targeting molecules, restriction endonucleases, antibodies and immunoglobulin-type agents, etc. Therefore, even if an EMS is not itself diagnostic for a pathological condition, the selective extinction or enhancement of the EMS based on selective modification of the sample may indeed play a role in the diagnosis.
However it is already applicable for the detection of infections by pathogenic bacteria in human and animal diseases, especially when there are no available molecular or serological methods of detection.
Patients suffering from chronic diseases such as rheumatoid arthritis, multiple sclerosis, Alzheimer's and Parkinson's diseases are generally positive for EMS in their plasma. However, freezing of the plasma will abolish the emission of EMS.
Therefore, the plasma has to be analyzed soon after separation from the drawn blood.
The present method described here is a significant improvement in that it allows detection of EMS from DNA extracted from plasma stored frozen.
The present application is a Continuation of U.S. patent application Ser. No. 14/706,336, filed May 7, 2015, now U.S. Pat. No. 9,316,610, issued Apr. 19, 2016, which is a Continuation of U.S. patent application Ser. No. 14/273,679, filed May 9, 2014, now U.S. Pat. No. 9,029,165, issued May 12, 2015, which is a Continuation of U.S. patent application Ser. No. 13/835,162, filed Mar. 15, 2013, issued May 27, 2014 as U.S. Pat. No. 8,736,250, which is a Continuation of U.S. patent application Ser. No. 12/560,772, filed Sep. 16, 2009, issued Mar. 26, 2013 as U.S. Pat. No. 8,405,379, which claims benefit of priority from U.S. Provisional Patent Application No. 61/098,405, filed Sep. 19, 2008, and U.S. Provisional Patent Application No. 61/098,227, filed Sep. 18, 2008, each of which is expressly incorporated herein by reference in its entirety.
Number | Name | Date | Kind |
---|---|---|---|
4708818 | Montagnier et al. | Nov 1987 | A |
4759929 | Chermann et al. | Jul 1988 | A |
4798797 | Montagnier et al. | Jan 1989 | A |
4839288 | Montagnier et al. | Jun 1989 | A |
5003000 | Bock et al. | Mar 1991 | A |
5030714 | Alizon et al. | Jul 1991 | A |
5030718 | Montagnier et al. | Jul 1991 | A |
5034511 | Alizon et al. | Jul 1991 | A |
5051496 | Alizon et al. | Sep 1991 | A |
5055391 | Montagnier et al. | Oct 1991 | A |
5066782 | Montagnier et al. | Nov 1991 | A |
5079342 | Alizon et al. | Jan 1992 | A |
5135864 | Montagnier et al. | Aug 1992 | A |
5169763 | Kieny et al. | Dec 1992 | A |
5173400 | Montagnier et al. | Dec 1992 | A |
5188963 | Stapleton | Feb 1993 | A |
5208321 | Hovanessian et al. | May 1993 | A |
5217861 | Montagnier et al. | Jun 1993 | A |
5221610 | Montagnier et al. | Jun 1993 | A |
5268265 | Montagnier et al. | Dec 1993 | A |
5304481 | Davies et al. | Apr 1994 | A |
5306614 | Alizon et al. | Apr 1994 | A |
5310651 | Alizon et al. | May 1994 | A |
5312902 | Montagnier et al. | May 1994 | A |
5358937 | Huynh Dinh et al. | Oct 1994 | A |
5364933 | Montagnier et al. | Nov 1994 | A |
5374519 | Montagnier et al. | Dec 1994 | A |
5403918 | Metz | Apr 1995 | A |
5407811 | Montagnier et al. | Apr 1995 | A |
5470702 | Hovanessian et al. | Nov 1995 | A |
5514542 | Nowinski et al. | May 1996 | A |
5545520 | Collandre et al. | Aug 1996 | A |
5545726 | Alizon et al. | Aug 1996 | A |
5550052 | Montagnier et al. | Aug 1996 | A |
5578715 | Alizon et al. | Nov 1996 | A |
5580739 | Alizon et al. | Dec 1996 | A |
5597896 | Montagnier et al. | Jan 1997 | A |
5610035 | Montagnier et al. | Mar 1997 | A |
5618701 | Landegren | Apr 1997 | A |
5626617 | Brewitt | May 1997 | A |
5629286 | Brewitt | May 1997 | A |
5672689 | Kieny et al. | Sep 1997 | A |
5677123 | Montagnier et al. | Oct 1997 | A |
5688637 | Moncany et al. | Nov 1997 | A |
5688646 | Montagnier et al. | Nov 1997 | A |
5698392 | Collandre et al. | Dec 1997 | A |
5747242 | Alizon et al. | May 1998 | A |
5770703 | Alizon et al. | Jun 1998 | A |
5773602 | Alizon et al. | Jun 1998 | A |
5786177 | Moncany et al. | Jul 1998 | A |
5795577 | Kieny et al. | Aug 1998 | A |
5807992 | Hovanessian et al. | Sep 1998 | A |
5824482 | Alizon et al. | Oct 1998 | A |
5830641 | Montagnier et al. | Nov 1998 | A |
5843638 | Montagnier et al. | Dec 1998 | A |
5858651 | Alizon et al. | Jan 1999 | A |
5866319 | Alizon et al. | Feb 1999 | A |
5869631 | Alizon et al. | Feb 1999 | A |
5874260 | Cleuziat et al. | Feb 1999 | A |
5889158 | Montagnier et al. | Mar 1999 | A |
5976785 | Alizon et al. | Nov 1999 | A |
6024734 | Brewitt | Feb 2000 | A |
6037165 | Montagnier et al. | Mar 2000 | A |
6048685 | Alizon et al. | Apr 2000 | A |
6054565 | Alizon et al. | Apr 2000 | A |
6056963 | Montagnier et al. | May 2000 | A |
6142927 | Clark | Nov 2000 | A |
6162439 | Alizon et al. | Dec 2000 | A |
6194142 | Moncany et al. | Feb 2001 | B1 |
6197496 | Montagnier et al. | Mar 2001 | B1 |
6232455 | Kroeger et al. | May 2001 | B1 |
6261571 | Hovanessian et al. | Jul 2001 | B1 |
6261762 | Alizon et al. | Jul 2001 | B1 |
6265149 | Montagnier et al. | Jul 2001 | B1 |
6284454 | Alizon et al. | Sep 2001 | B1 |
6296807 | Montagnier et al. | Oct 2001 | B1 |
6316183 | Alizon et al. | Nov 2001 | B1 |
6322964 | Cosand et al. | Nov 2001 | B1 |
6337179 | Alizon et al. | Jan 2002 | B1 |
6355789 | Alizon et al. | Mar 2002 | B1 |
6395495 | Montagnier et al. | May 2002 | B1 |
6399294 | Charneau et al. | Jun 2002 | B1 |
6426073 | Alizon et al. | Jul 2002 | B1 |
6428952 | Montagnier et al. | Aug 2002 | B1 |
6429306 | Montagnier et al. | Aug 2002 | B1 |
6485480 | Brewitt | Nov 2002 | B1 |
6514691 | Alizon et al. | Feb 2003 | B1 |
6518015 | Alizon et al. | Feb 2003 | B1 |
6541978 | Benveniste et al. | Apr 2003 | B1 |
6544728 | Alizon et al. | Apr 2003 | B1 |
6600023 | Montagnier et al. | Jul 2003 | B1 |
6608179 | Hovanessian et al. | Aug 2003 | B1 |
6627395 | Montagnier et al. | Sep 2003 | B1 |
6635752 | Alizon et al. | Oct 2003 | B2 |
6664041 | Montagnier et al. | Dec 2003 | B2 |
6724188 | Butters et al. | Apr 2004 | B2 |
6730304 | Alizon et al. | May 2004 | B2 |
6951648 | Alizon et al. | Oct 2005 | B2 |
6952652 | Butters | Oct 2005 | B2 |
6979535 | Alizon et al. | Dec 2005 | B2 |
6984721 | Montagnier et al. | Jan 2006 | B2 |
6995558 | Butters et al. | Feb 2006 | B2 |
7022814 | Moncany et al. | Apr 2006 | B1 |
7029679 | Alizon et al. | Apr 2006 | B2 |
7078516 | Moncany et al. | Jul 2006 | B1 |
7081747 | Butters et al. | Jul 2006 | B2 |
7115363 | Montagnier et al. | Oct 2006 | B1 |
7122188 | Montagnier et al. | Oct 2006 | B1 |
7157225 | Charneau et al. | Jan 2007 | B2 |
7205102 | Montagnier et al. | Apr 2007 | B1 |
7217508 | Wain-Hobson et al. | May 2007 | B1 |
7218764 | Vaisberg et al. | May 2007 | B2 |
7232654 | Chermann et al. | Jun 2007 | B1 |
7235353 | Mattheakis et al. | Jun 2007 | B2 |
7309589 | Montagnier et al. | Dec 2007 | B2 |
7323318 | Fan et al. | Jan 2008 | B2 |
7341731 | Montagnier et al. | Mar 2008 | B2 |
7412340 | Butters | Aug 2008 | B2 |
7507417 | Montagnier et al. | Mar 2009 | B2 |
7585619 | Alizon et al. | Sep 2009 | B1 |
7626013 | Alizon et al. | Dec 2009 | B1 |
7759477 | Moncany et al. | Jul 2010 | B2 |
7767800 | Alizon et al. | Aug 2010 | B2 |
7777020 | Moncany et al. | Aug 2010 | B2 |
7817840 | Mattheakis et al. | Oct 2010 | B2 |
8236324 | Charneau et al. | Aug 2012 | B2 |
8329396 | Alizon et al. | Dec 2012 | B1 |
8405379 | Montagnier | Mar 2013 | B1 |
8507196 | Alizon et al. | Aug 2013 | B1 |
8736250 | Montagnier | May 2014 | B1 |
9029165 | Montagnier | May 2015 | B1 |
9133525 | Montagnier | Sep 2015 | B2 |
9316610 | Montagnier | Apr 2016 | B1 |
20010006641 | Montagnier et al. | Jul 2001 | A1 |
20020022033 | Alizon et al. | Feb 2002 | A1 |
20020051967 | Montagnier et al. | May 2002 | A1 |
20020076691 | Alizon et al. | Jun 2002 | A1 |
20020086285 | Alizon et al. | Jul 2002 | A1 |
20020127144 | Mehta | Sep 2002 | A1 |
20020168628 | Alizon et al. | Nov 2002 | A1 |
20020169112 | Montagnier | Nov 2002 | A1 |
20020177128 | Alizon et al. | Nov 2002 | A1 |
20030049604 | Charneau et al. | Mar 2003 | A1 |
20030070604 | Holzrichter et al. | Apr 2003 | A1 |
20030082523 | Alizon et al. | May 2003 | A1 |
20030091985 | Alizon et al. | May 2003 | A1 |
20030170658 | Montagnier et al. | Sep 2003 | A1 |
20030186219 | Alizon et al. | Oct 2003 | A1 |
20030191061 | Brewitt | Oct 2003 | A1 |
20030224352 | Alizon et al. | Dec 2003 | A1 |
20030235835 | Alizon et al. | Dec 2003 | A1 |
20040010125 | Hovanessian et al. | Jan 2004 | A1 |
20040022781 | Spytek et al. | Feb 2004 | A1 |
20040038937 | Benveniste et al. | Feb 2004 | A1 |
20040111221 | Beattie et al. | Jun 2004 | A1 |
20050037340 | Moncany et al. | Feb 2005 | A1 |
20050158285 | Giampapa | Jul 2005 | A1 |
20050164173 | Montagnier | Jul 2005 | A1 |
20050203578 | Weiner et al. | Sep 2005 | A1 |
20050255129 | Montagnier | Nov 2005 | A1 |
20060035260 | Moncany et al. | Feb 2006 | A1 |
20060057616 | Montagnier et al. | Mar 2006 | A1 |
20060057699 | Munderloh | Mar 2006 | A1 |
20060078998 | Puskas et al. | Apr 2006 | A1 |
20060241392 | Feinstein et al. | Oct 2006 | A1 |
20070172927 | Montagnier et al. | Jul 2007 | A1 |
20070218489 | Sampath et al. | Sep 2007 | A1 |
20070248537 | Yang et al. | Oct 2007 | A1 |
20080039339 | Hassibi et al. | Feb 2008 | A1 |
20080213773 | Montagnier et al. | Sep 2008 | A1 |
20080261197 | Charneau et al. | Oct 2008 | A1 |
20080287856 | MacDonald et al. | Nov 2008 | A1 |
20090035757 | Owen et al. | Feb 2009 | A1 |
20090111159 | Brolaski et al. | Apr 2009 | A1 |
20090226891 | Nova et al. | Sep 2009 | A2 |
20100041011 | Van Agthoven et al. | Feb 2010 | A1 |
20100137474 | Goh et al. | Jun 2010 | A1 |
20100233296 | Benveniste et al. | Sep 2010 | A1 |
20100260677 | Bhatia et al. | Oct 2010 | A1 |
20100323391 | Montagnier et al. | Dec 2010 | A1 |
20110027774 | Montagnier | Feb 2011 | A1 |
20110076710 | Montagnier | Mar 2011 | A1 |
20110184025 | Hensel | Jul 2011 | A1 |
20120010859 | Spera | Jan 2012 | A1 |
20120024701 | Montagnier et al. | Feb 2012 | A1 |
20120071543 | Carter et al. | Mar 2012 | A1 |
20120185016 | Weiner et al. | Jul 2012 | A1 |
20120245084 | Carter et al. | Sep 2012 | A1 |
20130143205 | Montagnier | Jun 2013 | A1 |
20130196939 | Montagnier | Aug 2013 | A1 |
20130217000 | Montagnier | Aug 2013 | A1 |
20130224788 | Montagnier et al. | Aug 2013 | A1 |
20150132343 | Montagnier | May 2015 | A1 |
20150376724 | Montagnier | Dec 2015 | A1 |
20160002620 | Montagnier | Jan 2016 | A1 |
Number | Date | Country |
---|---|---|
1112748 | Jul 2001 | EP |
2700628 | Jul 1994 | FR |
2811591 | Jan 2002 | FR |
2894673 | Jun 2007 | FR |
2894673 | Jun 2007 | FR |
WO9417406 | Aug 1994 | WO |
WO9954731 | Oct 1999 | WO |
WO0001412 | Jan 2000 | WO |
WO0017637 | Mar 2000 | WO |
WO0017638 | Mar 2000 | WO |
WO0204067 | Jan 2002 | WO |
WO0204958 | Jan 2002 | WO |
WO2005119271 | Dec 2005 | WO |
Number | Date | Country | |
---|---|---|---|
61098227 | Sep 2008 | US | |
61098405 | Sep 2008 | US |
Number | Date | Country | |
---|---|---|---|
Parent | 14706336 | May 2015 | US |
Child | 15130484 | US | |
Parent | 14273679 | May 2014 | US |
Child | 14706336 | US | |
Parent | 13835162 | Mar 2013 | US |
Child | 14273679 | US | |
Parent | 12560772 | Sep 2009 | US |
Child | 13835162 | US |