The rethink(ip) guys (Matt, Steve and Doug) have announced a new patent caselaw portal, FedCirc.us. Currently, FedCirc.us is a website that allows professionals to access, digest and manage patent caselaw information. The site has reviews of patent decisions from the Supreme Court of the United States (SCOTUS) and the Court of Appeals for the Federal Circuit (CAFC).
One notable feature is GimmeTen! – press a button and get concise summaries of the last ten case reviews written…all on one page.
Matt says that a whole slate of informational products and services will be announced over the next several months so “Stay tuned“. You can bet we will.
A court has upheld a verdict that Abbott Laboratories infringed Innogenetics’U.S. Patent No. 5,846,704, which claims a method of genotyping the Hepatitis C Virus (“HCV”) by specifically hybridizing probes to a particular region of the HCV genome known as the 5 prime untranslated region (5′ UTR). The speed and relative inexpensiveness of the method disclosed in the patent make it possible for clinicians to learn quickly what particular genotype of HCV virus has infected their patient and thus, what antiviral medications will be most effective.
Hepatitis C viruses (HCV) are a family of positive-stranded, enveloped RNA viruses causing the majority of non-A, non-B (NANB) hepatitis. The ‘704 patent claims:
1. A method of genotyping HCV present in a biological sample comprising hybridizing nucleic acids in a biological sample with at least one probe and detecting a complex as formed with said probe and said nucleic acids of HCV, using a probe that specifically hybridizes to the domain extending from the nucleotides at positions -291 to -66 of the 5′ untranslated region of HCV.
The asserted novelty of the ‘704 patent is its disclosure of a method of gentotyping the HCV present in a particular biological sample. Although other researchers had developed methods of detecting HCV in the 5′ UTR, this assay can distinguish among different types and subtypes of HCV in a sample, using probes that hybridize specifically to the 5′ UTR of the HCV genome. This is a region of the HCV nucleic acid that other scientists knew could be used to detect the presence of HCV but had not realized could be used to determine and classify different HCV genotypes.
Abbott has been selling HCV genotyping assays that practice the method claimed in the ‘704 patent but do so using real-time polymerase chain reaction (PCR), a technology that it asserted was not covered by the ‘704 patent. Innogenetics obviously disagreed and filed suit.
On September 2, 2006, a jury returned a unanimous verdict for Innogenetics that the ‘704 patent was valid and the court has now determined damages and whether the infringement had been willful.
Now, the court has concluded that Abbott has not shown that it is entitled to a new trial on the issues of infringement or invalidity or to judgment as a matter of law on the issue of damages but that it is entitled to judgment as a matter of law on the issue of willful infringement. The court noted that:
Defendant conceded at the start of trial that it had no evidence to defeat plaintiff’s claim of infringement other than what was before the court on defendant’s motion for summary judgment, which I found insufficient to defeat the claim. Defendant conceded that it would be unable to prove obviousness to the jury in light of the court’s rulings and it failed to adduce sufficient evidence to persuade the jury that plaintiff’s ‘704 patent was invalid because it had been anticipated by the prior art. As to damages, plaintiff adduced sufficient evidence to support the jury’s award of $7,000,000 in damages. On the issue of willful infringement, however, plaintiff’s evidence was not sufficient to allow a reasonable jury to find that defendant acted willfully when it developed and sold its infringing products. Defendant is not entitled to a new trial on damages pursuant to Rule 60(b)(2) or (3) because it has not shown that plaintiff obtained its jury verdict through fraud or that newly discovered evidence would affect the outcome of the trial.
There seems to be a lot of angst these days over the U.S. patent system. Generally, complaints come from those who feel they can’t do whatever it is they want to do and they want new rules. Now, the Council on Foreign Relations has released a study, entitled “Reforming the U.S. Patent System: Getting the Incentives Right,” which blamed increased patent protection for a lack of new technology. “Over the past twenty-five years, American legislators and judges have operated on the principle that stronger patent protection engenders more innovation … this principle is misguided.”
The report, written by economist and University of Colorado professor Keith Maskus, claims the United States’ “overprotective patent system” has contributed to decreased competition among technology companies and has helped to stifle creativity and innovation. Basically, he argues that the oppressive burdens of the U.S. system are scaring away businesses. Maskus contends that increased litigation, overly broad patents and a laissez-fair antitrust policy regarding patents have all contributed to a downward spiral in competition. He feels that the recent increase in patent protection has not spurred innovation so much as it has impeded the development and use of new technologies. To support his views, he points to the fact that RIM agreed to pay $612.5 million to settle a patent suit that could have shutdown its Blackberry service. Admittedly, the USPTO had preliminarily ruled that all five NTP patents were invalid but RIM faced an increasingly nervous user base that didn’t clearly understand all the issues. RIM needed to placate its customers and potential customers to prevent a mass exodus to other services. This doesn’t necessarily prove a stifling of competition.The report also points to Chiron Corp.’s assertion of its hepatitis C-related patent as a prominent example of this trend. Basically, since Chiron has aggressively enforced its patent, critics claim that its enforcement has held up research by other firms and agencies for years. Although, the right to exclude others would seem to be a basic tenet of patent law.To resolve these problems, Maskus recommends reforms that include:
Change domestic patent policy in order to return to basic patenting principles and restore the system to one that encourages innovation rather than extraction of payments from legitimate competitors;
Abandon the high-level harmonization agenda, especially in free trade agreements; and
Mount a stronger global effort to deal with enforcement problems in developing countries through a combination of incentives and disincentives.
This return to basic patenting principles would include the creation of a competition advocacy office within the USPTO, limiting the grounds of a willful infringement finding, and awarding patents on a first-to-file rather than a first-to-invent basis.
The office of competition advocacy would be an office within USPTO to consider the economic implications of broad patent claims before they are granted but would be restricted to “patent applications on technologies that would have significant market power, an approach similar to the antitrust role of staff economists at the Federal Trade Commission and the Department of Justice.” Not sure who gets to decide what technologies, at the application stage, will trun out to have this significant market power. Also left unsaid is why the current antitrust reviews by the DOJ are inadequate.
In a lot of ways, the report reminds me of Winston Churchill’s remark that “Democracy is the worst form of government except for all those others that have been tried.” Churchill wasn’t really saying that democracy as a system of government was really great, he took a pragmatic approach that it’s not exactly wonderful for everyone but it’s the best we have to go on. If a better approach to the patent system comes along, I thing we should adopt it but it’s a waste of time to condemn the current system just out of spite.
One of the reasons the Patent Office is flooded with patent applications is that AMERICAN companies and universities, big and small, in every industry are in furious competitive races to beat out the competition, including inventing and patenting great and small. In one of the very few serious studies of software patents, Berkeley law and economics professors found no decrease in competition in the heavily patented software industry. Has RIM’s technology been stifled? No – just some of their money has been rearranged.
The current system only seems broken if the money is rearranged away from you.
When I did my Master’s thesis, I studied endocrine physiology in rats. Lots and lots of rats. Hence, I spent many a day preserving and fixing tissue samples and sitting at a microtome cutting slices of tissue for mounting on slides for staining. So, I felt a real affection for the recent patent case of Ventana Medical Systems v. Biogenex Laboratories (06-1074) .Ventana had appealed a judgment of noninfringement of U.S. Pat. No. 6,352,861 in favor of BioGenex claiming the district court erred in its claim construction. The patent at issue relates to automated methods and apparatuses for staining microscope slides. With immunostaining, you first mount tissue samples on microscope slides then treat the slides with various reagents such as antibody stains. The stained slides are examined to detect the presence of diseases.The ’861 patent claims automated apparatuses and methods used to perform a variety of biological assays, including immunostaining and Ventana filed suit against BioGenex alleging infringement of the ’861 patent.
The district court held a Markman hearing and construed certain disputed claim terms and the sole issue on appeal was the proper construction of the claim term “dispensing” in the ’861 patent. Claim 1 reads: “A method of dispensing reagents onto a slide…”
The district court construed the “dispensing” claim limitation to require “direct dispensing,” meaning that the reagent is dispensed directly from the reagent container onto the slide, rather than utilizing an intermediate transport mechanism to transfer reagent from the reagent container to the slide since the claim states that the reagent in the reagent container is dispensed onto the slide, meaning the reagent is dispensed directly from the reagent container.
After construing the term “dispensing” to mean “direct dispensing,” the district court held that the inventors disclaimed a particular type of dispensing, “sip and spit” dispensing, during the prosecution of an ancestor application. In “sip and spit” dispensing, an intermediate transport mechanism such as a pipette uses suction to “sip” the reagent from the reagent container and then releases or “spits” the reagent onto the slide.
The district court felt that the specification disclaimed the sip method in stating:
. . . Wakatake et al teaches reagent tables positioned side by side with a reaction table. (Wakatake et al, Figure 2). This side by side configuration precludes dispensing of the reagent “directly to a sample” or the incorporation of a “reagent delivery zone” as set forth in Claim 1 of the present invention. The Wakatake side by side configuration requires an additional device, a reagent pipetting device, to transfer the reagent between tables and mediate the dispensing of reagent to the sample. The reagent pipetting device is used to suck up an aliquot of reagent from a reagent container on one of at least two reagent tables, pivot so that the pipetting tube of the device is held just above a selected reaction vessel on a separate reaction table, and dispense the aliquot of reagent to the vessel (Wakatake at column 4, line 42 to column 5, line 10). Such devices are referred to in the trade as “sip and spit” devices.
On appeal, the CAFC stated that:
Claim terms “‘are generally given their ordinary and customary meaning.’” Phillips v. AWH Corp., 415 F.3d 1303, 1312 (Fed. Cir. 2005) (en banc) (quoting Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996)). And “the ordinary and customary meaning of a claim term is the meaning that the term would have to a person of ordinary skill in the art.” Id. at 1313.
The CAFC then agreed with Ventana that there is nothing in the record to suggest that a person of ordinary skill in the art would interpret the disclosure and claims of the ’861 patent to mean that the term “dispensing” is limited to “direct dispensing.” Although “direct dispensing” is one type of dispensing, other types of dispensing, such as “sip and spit” dispensing, also fall within the ordinary meaning of “dispensing.”
While BioGenex argued that the patent’s specification requires a narrow construction of “dispensing,” the CAFC held that this is not a case where the inventor’s distinguishing the invention over the prior art in the specification results in a disavowal of coverage by the inventor of features in the prior art:
“It is a ‘bedrock principle’ of patent law that ‘the claims of a patent define the invention to which the patentee is entitled the right to exclude.’” Phillips, 415 F.3d at 1312 (quoting Innova/Pure Water, Inc. v. Safari Water Filtration Sys., Inc., 381 F.3d 1111, 1115 (Fed. Cir. 2004)). “[A]lthough the specification often describes very specific embodiments of the invention, we have repeatedly warned against confining the claims to those embodiments.” Id. at 1323. While the fact that the disclosed embodiments are limited can assist in interpreting claim language, the mere fact that the ’861 patent discloses embodiments in which the reagent container is also the reagent dispenser does not in and of itself mean that the method claims at issue are limited to the disclosed embodiments.
In looking at the doctrine of prosecution disclaimer, the court said:
Accordingly, we examine the patent’s prosecution history, when placed in evidence, to determine whether the inventor disclaimed a particular interpretation of a claim term during the prosecution of the patent in suit or during the prosecution of an ancestor application. Id.; Advanced Cardiovascular Sys. v. Medtronic, Inc., 265 F.3d 1294, 1305-06 (Fed. Cir. 2001). But the doctrine of prosecution disclaimer generally does not apply when the claim term in the descendant patent uses different language.
The court didn’t buy it since claims 1 and 5 of the ’861 patent use different claim language — that is, they do not require that reagent be “dispensable directly to a sample” — the alleged disclaimer of “sip and spit” dispensing during the prosecution of the ’052 application does not apply to the asserted claims of the ’861 patent.
Eli Lilly & Co. had its patent on Zyprexa®, the world’s top- selling schizophrenia drug, upheld by the Court of Appeals for the Federal Circuit. The court affirmed a lower court decision that the patent is valid stating that for a chemical compound, a prima facie case of obviousness requires “structural similarity between claimed and prior art subject matter . . . where the prior art gives reason or motivation to make the claimed compositions.” Eli Lilly v. Zenith Goldline Pharmaceuticals, Inc. and Teva and Dr. Reddy’s (05-1396, -1429, -1430).
Lilly had sued for infringement of U.S. Pat. No. 5,229,382 after Zenith Goldline (now IVAX), Dr. Reddy’s Laboratories, and Teva Pharmaceuticals filed an Abbreviated New Drug Application (ANDA). The U.S. District Court for the Southern District of Indiana found the ’382 patent valid and infringed and the Appeals Court affirmed.
The ’382 patent claims both olanzapine and use of the compound to treat schizophrenia, i.e., 2-Methyl-10- (4-methyl-1-piperazinyl)-4H-thieno[2,3-b] [1,5] benzodiazepine, or an acid addition salt thereof. The defendants claimed an article in 1980 described (anticipated) claim 1 of the ’382 patent because it identified compounds from the same family of compounds (thienobenzodiazepines). However, the number of compounds actually disclosed by the reference numbers in the millions (including all proposed alternative substituents). It does provide a general structural formula with possible substituents of “R,” “R1,” and “R2,” but it does not define them at all. The court felt that no possible combination of those preferred substituents would lead to the components that make up olanzapine, because each would contain a fluorine or a chlorine.
In seeking to have the patent declared invalid based on obviousness, IVAX argued that the district court erred by erecting “a threshold requirement that defendants establish a teaching or incentive to treat the closest prior art (i.e., Compound ‘222) as a ‘lead compound.’” IVAX also claimed that the district court disregarded (1) the structural characteristic of olanzapine as the adjacent homolog of Compound ‘222, (2) the suggestions to delete fluorine from the prior art compound flumezapine, and (3) the observation that Compound ‘222 and flumezapine “bracket” olanzapine.
The CAFC avoided an issue with the KSR “teaching-suggestion-motivation” test stating that:
The factual underpinnings are: (1) the scope and content of the prior art, (2) the differences between the prior art and the claimed invention at the time of invention, (3) the level of ordinary skill in the art, and (4) the objective indicia of nonobviousness. See Graham v. John Deere Co., 383 U.S. 1, 17 (1966); Panduit Corp. v. Dennison Mfg., 810 F.2d 1561, 1566-67 (Fed. Cir. 1987). For a chemical compound, a prima facie case of obviousness requires “structural similarity between claimed and prior art subject matter . . . where the prior art gives reason or motivation to make the claimed compositions.” In re Dillon, 919 F.2d 688, 692 (Fed. Cir. 1990) (en banc). “[A] reasonable expectation of success, not absolute predictability” supports a conclusion of obviousness. In re Longi, 759 F.2d 887, 896 (Fed. Cir. 1985).
The CAFC held that the reference did not suggest or make obvious, among other things, olanzapine’s hydrogen component. The prior art references at the time of this invention taught away from using a non-halogenated compound as a substituent in the benzene ring, exactly where olanzapine has a hydrogen atom.
Also, the CAFC did not feel that IVAX proved that a person ordinarily skilled in this art would have selected Compound ‘222 as a lead compound because it contained hydrogen rather than fluorine or chlorine noting that at the time of invention, the state of the art would have directed the person of ordinary skill in the art away from unfluorinated compounds like Compound ‘222:
After all, the primary example of the state of the art at that time, the ’574 patent, did not provide any biological data for compound ‘222, suggested a preference for halogen-containing compounds, and identified a fluorine-containing compound, ethyl flumezapine, as “particularly active.” Findings of Fact and Conclusions of Law, slip op. at p. 170. Moreover, as the trial court detailed, Chakrabarti 1980a expressly taught that the addition of a fluorine or chlorine enhanced anti-psychotic activity. It also taught that the unfluorinated Compound ‘222 was less active than the benchmark compound, clozapine. Id. Thus, rather than providing the requisite motivation, the prior art taught away from selecting Compound ‘222 as a lead compound for further development.
Furthermore, the court felt that Lilly overcame any prima facie case of obviousness with extensive secondary considerations to rebut obviousness such as (1) a long-felt and unmet need; (2) failure of others; (3) industry acclaim; and (4) unexpected results.
The CAFC also looked at the trial court’s conclusion that Lilly’s clinical trials of olanzapine were not a public, but an experimental, use that negated any section 102 bar. Under section 102, a person is entitled to a patent, unless “the invention was . . . in public use . . . in this country, more than one year prior to the date of the application for patent in the United States.” 35 U.S.C. § 102(b).
In considering whether a particular use was “public” within the meaning of section 102(b), the CAFC held that several indicia may show the negating experimental character of a use, including (1) the length of the test period, (2) any confidentiality agreement, (3) any records of testing, (4) any monitoring and control of the test results, (5) the number of tests, and (6) the length of the test period in relation to tests of similar inventions. In this case, Lilly restricted access to the facility and closely monitored and confined the movements of the volunteers.
Matt Buchanan at Promote the Progress has an article on some clues about the direction in which patent reform will move once the 110th Congress convenes. Senator Leahy, the incoming chair of the Judiciary Committee, wants patent reform to include efforts “to increase access to essential medicines throughout the world” saying he intends “to redouble efforts to re-examine our patent laws in the hope that by making thoughtful and practical changes we can greatly increase access to essential medicines throughout the world.”
According to Leahy:
“We can help struggling families in developing nations, while improving US relations with large segments of the world’s population…The current global health crisis is one of the great callings of our time. Whether it is the Avian Flu, AIDS, SARS, West Nile Virus, or the approaching menace of multi-drug resistant bacteria, we need to recognize that the health of those half-way around the world now influences our security and affects our lives here in the United States….I want the work of the Judiciary Committee to be a catalyst to help make life-saving medicines more readily available around the world.”
Apparently, having the developed nations collectively help pay for such life-saving medicines by spreading the burden across all segments of society instead of asking pharmaceutical companies to foot the bill didn’t come up. I wonder if we’ll see a call to increased access to “life-saving software”?
Under current law, if a drug company wants to promote a new use of its drug, it can do so by submitting an efficacy supplement to the FDA and getting that use onto the label. Or, the company can rely on off-label prescriptions.
While federal law makes it illegal for drug companies to promote drugs for non-approved use, doctors have the right to prescribe what they consider the best treatment for their patients. This is where “off-label” use – that is using a drug approved for one condition to treat another – comes into practice. Today, more than one of seven prescriptions for common drugs are for off-label uses.
A lawyer handling the lawsuits of mentally ill patients is alleging that Eli Lilly carried on a campaign to influence doctors to prescribe its drug for off-label uses. The New York Times broke the story, citing internal documents from Eli Lilly and e-mail messages of its managers showing the company has allegedly been promoting off-label use of antipsychotic drug olanzapine (branded as Zyprexa) to treat dementia.
Currently, olanzapine is only approved by the FDA for the long-term treatment of schizophrenia, maintenance treatment of bipolar disorder, as well as treatment of certain types of acute episodes of bipolar disorder. Even so, Zyprexa is Lilly’s best-selling product with sales of $4.2 billion last year, accounting for 30 percent of its overall revenue. Not a bad return of the effort.
In response to the New York Times story, Lilly argues that numerous studies in the last ten years that the drug has been on the market performed by Lilly, government agencies such as the National Institute of Mental Health, and others, did not show a causal link between Zyprexa and diabetes.
Lilly contends that since Zyprexa was approved by the FDA in 1996, “the labeling provided to physicians identified the potentially clinically-significant weight gain that was observed in more than half of all patients treated long-term with Zyprexa, as well as the diabetes-related adverse events observed in clinical trials.”
Undeer current law, drug makers are barred from pitching doctors directly on unapproved uses of their drugs but, if a doctor or nurse asks a sales representative about it, those questions can be addressed. Companies can also sponsor continuing medical education (CME) sessions where off-label uses can be discussed.
The problem, of course, is that drug companies may push off-label uses of drugs harder than warranted given the evidence. Even if they follow the rules and only hand out journal articles, the information may not tell the whole story since they don’t have to also distribute less favorable studies.
It remains to be seen if the FDA will take action against activities by drug companies that promote off-label uses. If the FDA does take an aggressive stance on off-label use marketing, then it could significantly impact drug sales for companies whose revenues are derived in large part by such off-label use.
President Bush gave out an early Christmas present to the biotech industry on Tuesday after signing a bill that creates a somewhat controversial bureaucracy that would give tax dollars to private companies and universities to develop vaccines and treatments. The bill, the “Pandemic and All-Hazards Preparedness Act” (S. 3678) creates the Biomedical Advanced Research and Development Agency (BARDA), which will dole out $1.07 billion over two years to be used to help biotechnology companies make the leap from initial research to market ready – a gap known now as the “Valley of Death.”
Earlier, Congress appropriated $3.3 billion for pandemic preparation. Project Bioshield, created in 2004, set aside $5.6 billion over 10 years for drugs against bioterrorism threats such as anthrax, smallpox, and the plague. Project Bioshield was intended to promote the development of medical defenses against biological, chemical, and radiological weapons by guaranteeing that the government would buy promising products, which otherwise would be unlikely to find a market. Large pharmaceutical companies have shown little interest in pursuing BioShield contracts so contracts have gone to smaller companies.
The problem remained that most companies didn’t want to take on all the risk of the drug development process for a chance at the sale. The cost of the liability (and, hence, liability insurance) in relation to the projected profit margin made the deal unattractive to most companies. It is noteworthy that eighteen percent of all biotechnology companies rate the cost of product liability insurance as the most important problem facing their firms. It is hoped that BARDA will help fund the early development and share in the risk. The legislation says the HHS Secretary will coordinate the product research and development by:
facilitating collaboration between HHS and other agencies, industry, academia, and other persons, with respect to such advanced research and development;
promoting countermeasure and product advanced research and development;
facilitating contacts between interested persons and the offices or employees authorized by the Secretary to advise such persons regarding requirements under the Federal Food, Drug, and Cosmetic Act; and
promoting innovation to reduce the time and cost of countermeasure and product advanced research and development.
The Act will also reform the contracts authorized by Project BioShield to include advanced payments worth up to 5 percent of the value of a contract. It will also create exemptions from anti-trust laws for such work developing and manufacturing countermeasure products. That provision is set to end six years after enactment.
The bill was supported in Congress by Sen. Richard Burr, R-N.C., who spent the last two years trying to create a program acceptable both to biotechnology companies and to the public. There were lots of critcs to the original language that would have exempted BARDA from the Freedom of Information Act when no other government agency has such a broad veil of secrecy.
The act signed into law contains a provision prohibiting disclosure of “technical data or scientific information” that would reveal vulnerabilities of the nation’s defenses that aren’t publicly known. Defining that trigger is up to the secretary of health and human services.The legislation limits any disclosure of “specific technical data or scientific information that is created or obtained during the countermeasure and product advanced research and development carried out under subsection (c) that reveals significant and not otherwise publicly known vulnerabilities of existing medical or public health defense against biological, chemical, nuclear, or radiological threats.”
The Federation of American Scientists fears the secrecy could prevent any information from coming out.Meanwhile, the Department of Health and Human Services (HHS) has canceled its $877.5 million contract with VaxGen Inc. for a new anthrax vaccine, after problems with the vaccine’s stability caused the company to miss a critical deadline for starting a clinical trial. Because of concerns about the vaccine’s stability, the Food and Drug Administration (FDA) refused to allow VaxGen to start a Phase II Clinical Trial on Dec 18, as required by HHS so the government terminated for default.
The contract, awarded in 2004, called for VaxGen to produce 75 million doses of a new anthrax vaccine — enough to immunize 25 million people. The hope was that the vaccine would improve on the anthrax vaccine used by the US military, called anthrax vaccine adsorbed (AVA). The VaxGen vaccine is based on a recombinant form of protective antigen (rPA), a key anthrax protein. It was expected to provide immunity in 3 doses, rather than the 6 doses required for AVA, and to cause fewer side effects.
Editor-in-Chief Barista Stephen Jenei is a patent attorney and Owner of Jenei LLC. When not serving up patent chat over a steaming cup of java, he's handling a diverse intellectual property practice in the biotechnology, pharmaceutical and chemical fields. More info @ Jenei LLC
The rethink(ip) guys (Matt, Steve and Doug) have announced a new patent caselaw portal, FedCirc.us. Currently, FedCirc.us is a website that allows professionals to access, digest and manage patent caselaw information. The site has reviews of patent decisions from the Supreme Court of the United States (SCOTUS) and the Court of Appeals for the Federal Circuit (CAFC).
The ’382 patent claims both olanzapine and use of the compound to treat schizophrenia, i.e., 2-Methyl-10- (4-methyl-1-piperazinyl)-4H-thieno[2,3-b] [1,5] benzodiazepine, or an acid addition salt thereof. The defendants claimed an article in 1980 described (anticipated) claim 1 of the ’382 patent because it identified compounds from the same family of compounds (thienobenzodiazepines). However, the number of compounds actually disclosed by the reference numbers in the millions (including all proposed alternative substituents). It does provide a general structural formula with possible substituents of “R,” “R1,” and “R2,” but it does not define them at all. The court felt that no possible combination of those preferred substituents would lead to the components that make up olanzapine, because each would contain a fluorine or a chlorine.