Source: https://www.patentdocs.org/2007/04/index.html
Timestamp: 2019-04-18 10:42:14+00:00

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In an eagerly awaited decision regarding the Federal Circuit's "teaching, suggestion, or motivation" (TSM) test for analyzing obviousness, the Supreme Court on Monday issued its ruling in KSR Int'l Co. v. Teleflex Inc. In a 24-page opinion, the Court reversed the Federal Circuit's determination of validity with respect to claim 4 of U.S. Patent No. 6,237,565 and found the claim to be invalid as obvious under 35 U.S.C. § 103.
Teleflex initiated the present litigation when it accused KSR of infringing claim 4 of the '565 patent. KSR, in turn, countered that this claim was invalid as obvious. The District Court granted summary judgment in KSR's favor, finding "little difference" between the combined teachings of the prior art and the asserted claim. In addition to analyzing the issue pursuant to Graham v. John Deere Co. of Kansas City, the District Court also found claim 4 to be obvious under the Federal Circuit's TSM test.
The Federal Circuit reversed, determining that the District Court had not been "strict enough" in applying the TSM test. In particular, the Federal Circuit found that the District Court had failed to make "finding[s] as to the specific understanding or principle within the knowledge of a skilled artisan that would have motivated one with no knowledge of [the] invention" to make the claimed combination.
The Supreme Court began its analysis by rejecting the Federal Circuit's "rigid" application of the TSM test in the present case, stating that "[t]hroughout this Court's engagement with the question of obviousness, our cases have set forth an expansive and flexible approach inconsistent with the way the Court of Appeals applied its TSM test here." After discussing three of its post-Graham decisions (United States v. Adams; Anderson's-Black Rock, Inc. v. Pavement Salvage Co.; and Sakraida v. AG Pro, Inc.), the Court concluded that its precedents make clear that a proper analysis "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ."
It is important to note that while the Court rejected the Federal Circuit's "rigid" application of the TSM test in the present case, the Court did not discount that the test might serve as a useful analytical device in the context of a proper obviousness analysis. In fact, the Supreme Court observed that when the Federal Circuit's predecessor first established the TSM test, it had "captured a helpful insight," and further, that "[t]here is no necessary inconsistency between the idea underlying the TSM test and the Graham analysis." The Court concluded, however that "[h]elpful insights . . . need not become rigid and mandatory formulas; and when it is so applied, the TSM test is incompatible with our precedents."
Note: Patent Docs plans to provide additional commentary regarding this important Supreme Court decision and its impact on biotech/pharma patent prosecution and litigation in the coming days and weeks.
Wyeth v. Osmotica Pharmaceutical Corp.
Infringement of U.S. Patent Nos. 6,403,120 ("Extended Release Formulation of Venlafaxine Hydrochloride," issued June 11, 2002) and 6,419,958 (same title, issued July 16, 2002) based on Osmotica's filing of an NDA (under § 505(b)(2) of the Food, Drug and Cosmetic Act) to manufacture a generic version of Wyeth's Effexor® XR (venlafaxine hydrochloride, used to treat depression). View the complaint here.
On Thursday, CEL-SCI Corporation announced that it had been granted U.S. Patent No. 7,199,216 by the U.S. Patent & Trademark Office. The '216 patent relates to conjugated peptides in which an antigenic peptide that is associated with an immune disorder is covalently bonded to a T-cell binding ligand that has been modified to inhibit or suppress the activation of the class or subclass of T-cells to which the antigenic peptide selectively binds. The conjugated peptides of the '216 patent can be used to decrease or completely retard undesirable immune response outcomes such as autoimmune diseases, asthma, allergy, or transplantation rejection.
According to the statement released by CEL-SCI, the '216 patent covers the company's T-cell modulation platform technology known as AdapT (for Antigen Directed Apoptosis), which uses peptide constructs to selectively cause the death of immune T-cells involved in autoimmune disease, asthma, allergy, and transplant rejection, by forcing these disease-causing T-cells to undergo apoptosis (programmed cell death) and anergy (a state of immune unresponsiveness). CEL-SCI's AdapT constructs exploit the fact that T-cells receiving only one of two signals required for T-cell activation will undergo apoptosis. In particular, while one peptide component of the AdapT constructs engages the antigen-specific T-cell receptor, the other peptide component blocks and inhibits the second signal needed for activation of disease-causing T-cells.
wherein z is a direct bond or a divalent linker and X represents an amino acid other than Lys.
The sanctimony continues over the U.S. Patent and Trademark Office re-examination of the Thomson stem cell patents. This time, it is an article by Constance Holden in the April 13, 2007 issue of Science. Although refreshingly factual, it manages in ways both frank and subtle to create the (false) impression that stem cell patenting is a bad idea.
The primary alleged offenses are two: first, that these patents impede scientific research, and second that commercial licenses are too high. The first allegation is supported by complaints from scientists about the material transfer agreements (MTAs) associated with licensing stem cells covered by the Thomson patents from the Wisconsin Alumni Research Foundation (WARF). Although the article acknowledges that "[m]ost scientists doing basic stem cell research in academic or government labs are minimally restricted by WARF's current policies, which require them to pay only $500 for a batch of Wisconsin cells," the process is burdened by too much "red tape." (This allegation is preciously illustrated by a toll booth labeled "WARF" through which nonprofit researchers can pass, but they are festooned with said red tape.) These allegations ignore the fact that the agreement used by WARF was developed with the participation of the National Institutes of Health (NIH) and is consistent with (and in some ways, more lenient than) MTAs commonly used between university tech transfer offices. It also ignores the amount of time and effort WARF spends in training recipients of its cells, which are notoriously difficult to handle and propagate to retain their "stemness." Also unspoken is any acknowledgement that WARF's program (in conjunction with the NIH) has permitted stem cell scientists in federally funded laboratories to continue to do their work in the face of the Bush administration's restrictive prohibitions on stem cell science. Significantly, WARF imposes no restrictions on patenting or publishing the results of basic academic research.
Claim 1 of the '607 patent: A method of modulating the differentiation of undifferentiated, pluripotent human embryonic stem (hES) cell in culture, comprising providing a fibroblast feeder layer which has been selected based on its ability to induce differentiation of undifferentiated, pluripotent human embryonic stem (hES) cells in culture, and growing said undifferentiated, pluripotent human embryonic stem (hES) cells on said fibroblast feeder layer, wherein said fibroblast feeder layer modulates the differentiation of said undifferentiated, pluripotent human embryonic stem (hES) cell in culture.
Claim 1 of the '822 patent: A method of transplanting human ES derived neural progenitor cells in into a host, said method comprising: obtaining undifferentiated or pluripotent human embryonic stem cells; culturing the cells in the presence of serum free medium supplemented with B27 and growth factors comprising EGF and bFGF to obtain neural progenitor cells comprising expressed markers of primitive neuroectoderm and neural stem cells; and injecting the neural progenitor cells into the central nervous system of the host.
Claim 1 of the '437 patent: A method of producing a human neural progenitor cell from a human ES cell, said method comprising: obtaining a source of an undifferentiated human ES cell; and culturing the ES cell in the presence of an antagonist of a BMP mediated default pathway of extra embryonic endoderm differentiation to differentiate the ES cell to a progenitor cell, wherein said progenitor cell lacks at least one marker of said undifferentiated ES cell; and culturing the progenitor cell in a neural progenitor cell culture medium to obtain a neural progenitor cell.
The owner of these patents, ES Cell International of Singapore, provides the same human embryonic stem cells provided by WARF, but at a cost of $6,000. Licensing terms for these patents and whether any licenses are available or have been granted are unknown, but the company is "underpinning its position in the stem cell biotechnology arena through aggressive implementation of its Patent and Intellectual Property Strategy" according to its website.
Predictably, the loudest complaints come from commercial interests, who cite licensing fees of (gasp!) "up to $400,000," according to Jonathan Auerbach of GlobalStem, Inc. (GlobalStem is reported to have avoided the Thomson patents by using stem cells having abnormal karyotypes.) Unspoken is the reality that these types of licensing fees are not particularly onerous for a commercial concern, particularly when licensing a patented reagent as potentially valuable as a stem cell. Also common are the types of "reach through" provisions for products made using stem cells contained in WARF's commercial licenses; since the commercial entities will typically be selling such products (be they biochemicals produced by the cells or differentiated cells or tissues made from stem cells), it would be unrealistic (and inequitable) for a company to obtain the cells for a simple licensing fee and insulate its commercial products from royalty obligations. Similar considerations apply to the complaints of Robert Lanza (at left) of Advanced Cell Technologies, Inc. (ACT), that WARF requires a $5,000 fee when ACT sells stem cells to third parties. Mr. Lanza ignores the fact that most MTAs preclude ownership, much less transfer, of the material by the licensee, or that ACT's cells benefit from being within the Federal government's stem cell ban as a result of WARF's provenance over these cell lines. (Unmentioned in the article is ATC's market cap of $42M.) Mr. Lanza complains that WARF exclusively licensed the Thomson patents to Geron Corporation for certain indications, but gives no reason (because there really are no reasons) why this isn't a commonplace consequence of patent licensing.
The immediate fate of the Thomson patents will take at least until the end of the year, when the U.S. Patent and Trademark Office is expected to determine whether any of the Thomson patent claims are patentable after considering WARF's responses to the first round of Office Actions in both the ex parte and inter partes interferences.
In an April 26, 2007 press release SciClone Pharmaceuticals Inc. announced that it acquired exclusive rights in the U.S. and Canada to develop and commercialize a compound in the clinical stage for treatment of pancreatic cancer. The drug, RP101, was brought to Phase I clinical trials as a combination treatment with gemcitabine by Resistys, Inc., a wholly-owned subsidiary of Avantogen Oncology, Inc. In acquiring the rights to RP101 from Avantogen, SciClone expects to initiate a Phase II clinical study to assess the compound's effectiveness in treating late-stage pancreatic cancer by the end of 2007.
Under the terms of the agreement, SciClone receives exclusive development and commercialization rights in the U.S. and Canada, in exchange for payments to Resistys, including an upfront payment of about $1.7 million, a $1.3 million milestone payment upon initiation of the Phase II clinical study, post Phase III regulatory and commercial payments of up to $22 million, and royalty payments on future sales.
Bristol-Myers Squibb Co. and Pfizer Inc. announced today that the companies will be entering into two separate collaborations. In the first, the two companies will be working together to develop and commercialize Bristol-Myers Squibb's anticoagulant, apixaban. In the second, the collaboration will focus on the research, development, and commercialization of pre-clinical compounds identified in Pfizer's metabolic disorder discovery program.
With respect to the apixaban collaboration, Pfizer will be making an upfront payment of $250 million to Bristol-Myers Squibb and will be funding 60% of all future developmental costs. Under the terms of the agreement, Bristol-Myers Squibb could receive additional payments of up to $750 million from Pfizer depending on the attainment of development and regulatory milestones. With regard to the commercialization of apixaban, the companies will share expenses and profits/losses equally.
Apixaban is an inhibitor of factor Xa, which plays a role in the coagulation cascade. According to the Bristol-Myers Squibb release, apixaban has entered Phase III clinical trials to investigate the use of the compound to prevent venous thromboembolism (the process by which blood clots travel through the veins) and stroke in patients with atrial fibrillation (abnormal heart rhythm), and has entered Phase II clinical trials to investigate the use of the compound to treat acute symptomatic deep vein thrombosis and to prevent cardiovascular events in patients with acute coronary syndrome.
With respect to the metabolic disorder collaboration, Pfizer will be responsible for early-stage research and development, and the companies will jointly conduct Phase III development and commercialization activities. Under the terms of the agreement, Bristol-Myers Squibb will be making an upfront payment of $50 million to Pfizer and will be responsible for 40% of the expenses for Phase III development and commercialization. The companies will split profits/losses on a 60-40 basis, with Pfizer taking or assuming the larger share.
Additional information regarding the collaboration can be found in Bristol-Myers Squibb's press release and in Pfizer's press release.
The end of the consolidated omeprazole litigation may have been reached this week, when the Federal Circuit ruled on AstraZeneca's appeal over the validity of U.S. Patent No. 6,013,281. In its decision, the Court majority (Judges Rader and Bryson) upheld the District Court's finding that the '281 patent claims at issue were invalid as being inherently anticipated by a Korean patent publication, over a strong dissent by Judge Newman.
Unlike earlier incarnations of the dispute, which named several defendants, this case named generic pharmaceutical maker Andrx as the sole alleged infringer. The patent claims at issue recited AstraZeneca's formulation method for omeprazole. This formulation contains an alkaline reacting compound (ARC) to protect acid-sensitive omeprazole during transit through the stomach. The Federal Circuit affirmed the District Court's finding that Andrx infringed, but also affirmed the District Court's determination that AstraZeneca's claims were invalid for being either anticipated or obvious.
The claimed process was directed at the formation of a water-soluble separating layer between the acid-sensitive omeprazole core and the enteric coating, wherein the separating layer was formed in situ by a reaction between the ARC in the core and the enteric coating. As the Federal Circuit explained, "the '281 process produces an omeprazole formulation with three distinct layers, but starts with only two of the three layers," wherein the reaction produced a separating layer comprising a salt form of the enteric coating material. Independent claim 1 recited a minimum ARC concentration in the core required to form the separating layer, and dependent claims recited specific ARC compounds. Significant to the Federal Circuit's decision, the '281 specification contained process parameters (including temperature) not recited in the claims.
The prior art the District Court found invalidating was a Korean patent application that was in the art two years before AstraZeneca's earliest priority date. This patent application was not unknown to AstraZeneca, because it had been the basis for a lawsuit in Korea between AstraZeneca and the Korean applicant, Chong Kun Dan (CKD) Corp. over one of AstraZeneca's own Korean omeprazole formulation patents. CKD's patents did not provide any process conditions, which CKD was allowed to keep as trade secrets under Korean patent law. However, AstraZeneca's own testing done with regard to this Korean action supported the conclusion that the CKD formulation indeed contained a separating layer (albeit, according to AstraZeneca, a conventionally-applied layer), and AstraZeneca scientists testified to that effect in the Korean action. CKD's scientists steadfastly maintained throughout that their formulation did not contain a separating layer.
It was undisputed that AstraZeneca's inventors were unaware of the process conditions used by CKD when they conceived the '281 invention. After the AstraZeneca inventors determined the proper conditions for producing a separating layer in situ they became aware of CKD's conditions, which differed from their own and did not produce a separating layer in situ. One important difference was the formulation temperature: 42ºC using AstraZeneca's process and 70ºC using CKD's process.
Despite these differences, the District Court found the CKD patent application to be invalidating. The District Court's basis for finding anticipation was the disclosure in the CKD application of all the limitations of Claim 1 of the '281 patent except the phrase "forming in situ a separating layer." AstraZeneca contended that this phrase implicated the process steps recited in the '281 specification, specifically the 42ºC inlet air temperature, which was not disclosed in CKD's application. The District Court declined to import the temperature limitation into the claim, discerning no basis for doing so. Instead, the District Court determined whether the limitation in the disputed phrase was inherently disclosed in CKD's application not from the reference itself, but using AstraZeneca's assertions made in the Korean infringement action. Specifically, the District Court relied upon expert testimony by AstraZeneca's witnesses in the Korean action, that CKD's formulation contained a separating layer that was inherently produced by its formulation. These admissions were coupled by the District Court with testimony from Andrx's expert that a separating layer would form in CKD's formulation "each and every time," and the absence of contrary experimental evidence from AstraZeneca at trial. Moreover, AstraZeneca's trial expert's contrary testimony was proffered in the absence of his consideration of AstraZeneca's earlier testimony and other evidence from the Korean action, permitting the District Court to discount his testimony.
The Federal Circuit affirmed, applying its clear error standard of review for the factual findings made by the District Court. The presence of a separating layer in the CKD formulation was deemed inherent from the combination of the ingredients specified in CKD's Korean patent application, and thus the absence of any disclosure of the process by which CKD made its formulation was determined to be without any significance. The CAFC also affirmed the District Court's obviousness determination for AstraZeneca's dependent claim 9, which recited different ARC species than were disclosed in the CKD patent application. According to the CAFC, the District Court was correct in holding that there was no patentable difference between the ARC disclosed by CKD (arginine) and the ARC's recited in AstraZeneca's dependent claim 9 (alkaline salts of phosphoric acid, carbonic acid, or silicic acid).
Judge Newman was strenuous in her dissent. For her, the fact that the CKD Korean application does not disclose formulation conditions, much less describe AstraZeneca's conditions, and that it is "undisputed" that the practice of the disclosed CKD formulation does not produce a separating layer, was dispositive. The mere possibility that the cited art could produce the claimed product or that the skilled worker might be able to arrive at the claimed process from the teachings of the reference is not enough. While Judge Newman focused on whether the CKD patent application disclosed the process (which she determined did not), the majority agreed with the District Court that the presence of the recited ingredients was sufficient to produce a separating layer "each and every time" according to unrefuted (or at least insufficiently refuted) trial testimony. Curiously, the affirmative statements by Andrx's expert that formulations made according to CKD's patent specification would inherently produce a separating layer were unverified by experimental evidence, and as Judge Newman points out, were contrary to the conclusions of the Korean tribunal and CKD's own expert. Judge Newman also argued that the CKD application is not enabling, since it does not disclose the conditions necessary for preparing its formulations. Finally, Judge Newman was troubled by the majority's use of "secret information," i.e., the formulation conditions admittedly not disclosed in the CKD patent application.
Judge Newman has the better legal argument, but it is clear that AstraZeneca was defeated by a combination of poor claim drafting, its own prior inconsistent admissions, and the CAFC's standard of review. The fact that AstraZeneca's inventors were "spurred on" in their own developmental work by their belief that CKD inherently produced a separating layer in situ may also have been a consideration. AstraZeneca did not prevail, however, at least in part because the process limitations it relied upon at trial, including the inlet air temperature, were not recited even in a dependent claim. Under these circumstances, the clear lesson is to include process limitations in at least some dependent claims to a process, if a patentee intends to rely upon these limitations to distinguish over the prior art.
Luminex Corporation announced that it received a non-exclusive license from Johns Hopkins University with rights to use the University's patented cystic fibrosis (CF) genetic markers. CF is a chronic autosomal recessive disorder affecting the lungs and digestive tract caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein.
The license rights apply to technology that is included in the Tag-It® Cystic Fibrosis Kit from Luminex Molecular Diagnostics (formerly Tm Bioscience). The Tag-It® technology aids diagnosis and screening of CF in newborns, children, and can be used to determine whether an adult is a carrier of CF. The license from Johns Hopkins provides the rights to four mutations (549N, 551D, 553X, and 559T) which are included in the Cystic Fibrosis Kit, and covers two mutations (551D, 553X) in a screening panel of 23 cystic fibrosis gene mutations.
Specific terms of the license agreement were not disclosed in Luminex's press release.
Cytos Biotechnology AG has granted a worldwide, exclusive license to Novartis to develop, manufacture, and commercialize its therapeutic vaccine for nicotine addiction, CYT002-NicQb. The vaccine is currently in Phase II clinical development. Cytos may receive upfront and milestone payments, as well as royalty payments, based on the successful commercial launch and sales of CYT002-NicQb. The agreement is subject to regulatory review before final approval. The press release can be viewed here.
SinoBiomed announced today that the U.S. Patent & Trademark Office has issued U.S. Patent No. 7,101,556, which is directed to fusion proteins comprising the Plasmodium merozoite surface protein-1 (MSP1) and the Plasmodium apical membrane antigen 1 (AMA-1) and the production of anti-malarial vaccines using such proteins. In its release, SinoBiomed states that the '556 patent covers the malaria vaccine PfCP2.9, the exclusive rights to which SinoBiomed acquired through its subsidiary, Shanghai Wanxing Bio-pharmaceuticals Co. Ltd. Shanghai Wanxing Bio-pharmaceuticals had previously acquired the rights to the '556 patent from assignee Second Military Medical University.
Although the '556 patent issued last fall, SinoBiomed's statement is likely timed to coincide with news that its PfCP2.9 vaccine had been approved for Phase II clinical trials to be conducted in Ghana this summer by the Chinese State Food and Drug Administration (SFDA) - which SinoBiomed notes has a drug approval process similar to that of the U.S. FDA. In Phase I clinical trials, the vaccine, which targets the malaria parasite Plasmodium falciparum during its replication stage in human red blood cells, showed greater immunogenicity and fewer adverse reactions than other malaria candidate vaccines being tested. The Shanghai-based biotech company is developing and testing the vaccine with the support of the World Health Organization (WHO), the Malaria Vaccine Initiative (MVI) of the Program for the Appropriate Technology in Health (PATH), and the Bill & Melinda Gates Foundation, the latter of which has committed $258.3 million to the global fight to eradicate malaria.
The possible impact of SinoBiomed's research becomes clear when one learns that malaria threatens more than 2 billion people globally and kills more than a million people a year - most of whom are children. Further complicating matters is the fact that the treatment and control of malaria has become more difficult with the spread of drug-resistant strains of parasites and insecticide-resistant strains of mosquito vectors.
(ii) isolating the polyclonal antibody.
The USPTO released this pre-OG notice regarding its electronic priority document exchange program (PDX) implemented in conjunction with the European Patent Office (EPO). This program is intended to benefit applicants that have filed an application with the U.S. or European Patent Offices (a "priority document"), and subsequently wish to file a corresponding application in Europe or the U.S. within 12 months of the first filed application. This document exchange program is free to applicants (avoiding the prior $20 administration fee).
The notice contains a bit more explanation regarding how and when to make the request for priority document exchange, as a number of submitted requests have apparently been made improperly, and thus, gone unfulfilled. I admit (only somewhat sheepishly) that I fall into the category of those who have failed to make a proper request under the new program. In any case, the USPTO clarifies that form PTO/SB/38 should be used when an applicant wishes to have the USPTO electronically retrieve a copy of a priority document from the EPO. Importantly, the USPTO will not attempt to retrieve a copy of the document until the document is identified in an oath/declaration or application data sheet (ADS) in compliance with 37 C.F.R. § 1.63(c). The USPTO's receipt of the electronic copy of the priority document will satisfy the requirement of 37 C.F.R. § 1.55 (providing the Office with a certified copy of the priority document).
In the reverse situation, an applicant can also request that the EPO make a request to retrieve an electronic copy of a U.S. patent application to which an EP patent application claims priority. However, the EPO will only retrieve copies of a priority document when (1) the USPTO receives written authorization to "permit access" under 37 C.F.R. § 1.14(h) and 35 U.S.C. § 122, if the application is not published; or (2) the U.S. application is published or issued as a patent. The USPTO clarifies in the notice that form PTO/SB/39 should be filed in the relevant U.S. application(s) in order to provide proper authorization to permit access to the application by "participating offices."
The notice provides telephone and e-mail (PDX@uspto.gov) contact information should one have additional questions.
On Friday, April 27, 2007 at 9:00 am, the Seton Hall University School of Law (SHU Law) will hold a press conference to announce the establishment of the Center for Health & Pharmaceutical Law. The mission of the new Center will be "to address the evolving legal and public policy framework of modern drug and device regulation and practice."
As reported by the Associated Press, the Center will be funded primarily by endowments totaling more than $8 million from Bristol-Myers Squibb, Johnson & Johnson, Sanofi-Avenis, and Schering-Plough. Bristol-Myers Squibb itself will be donating $5 million to endow a professorship in corporate governance and business.
The research and policy center will focus on various issues affecting the pharmaceutical and medical device industries, including legal, business ethics, regulatory, enforcement, among others. According to Ms. Denise Pinney, who is the Assistant Dean of Health, Science, and Technology Law at SHU Law, the research will include not only the view of industry personnel and legal scholars, but also the views of patients, doctors, politicians, and students.
More information about the press conference can be found here.
AstraZeneca PLC announced on Monday that it plans to acquire MedImmune Inc. in a deal estimated to be worth about $15 billion. AstraZeneca expects that this acquisition, in combination with its earlier acquisition of Cambridge Antibody Technology (CAT) will place it among the top biologics companies in the world, accelerating its biologics strategy. The company now will be able to approach its research and development strategy through well developed small molecule, biologic, and vaccine technologies. The acquisition of MedImmune should provide several immediate benefits to AstraZeneca, including adding personnel having experience with the regulatory issues involved with Biologics License Applications; acquiring facilities having large capacity for biologics manufacturing and protein engineering; increasing revenue from sales of existing products including Synagis®, FluMist®, and anticipated sales from Numax®; and expanding its biologics pipeline from 7% to 27%.

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