Enanta. v. Pfizer: Alcohol analogy best for explaining 2≠1?

Enanta Pharma. Inc. v. Pfizer Inc., No. 2025-1427 (June 23, 2026)

“[Enanta] did not invent what they did not disclose.”

Boom! Enanta’s provisional patent application did not disclose -NCH(O)-C₁-alkyl. It only recited -NCH(O)-C₂-C₁₂-alky. Therefore, it did not support Enanta’s non-provisional patent disclosure of -NCH(O)-C₁-C₁₂-alkyl. In between filing dates, Pfizer disclosed Nirmatrelvir, a.k.a. PF-07321332¹ in Paxlovid®, comprising a -NCH(O)-CF₃ substituent, which is a -NCH(O)-C₁-alkyl. One carbon made a big difference.

The court followed this conclusion with the following analogy:

“The issue in this case is akin to asking whether a disclosure of ethanol, a two-carbon alcohol regularly consumed by people, would provide adequate written description support for methanol, a one-carbon alcohol that is highly toxic to people.”

Fair point. Chemistry is often understood as an unpredictable art. Simply adding one atom to a molecule can significantly change its activity. Magic methyls are indeed real for various properties of various chemical compounds. Indeed, here the methanol/ethanol analogy was decidedly persuasive. Logically in this case, if ethanol (CH₃CH₂OH), which is a -C₂-alkyl-OH, cannot support methanol (CH₃OH), which is a -C₁-alkyl-OH, then -NCH(O)-C₂-C₁₂-alkyl cannot support -NCH(O)-C₁-C₁₂-alkyl.

However, even though this methyl/ethyl alcohol analogy was persuasive, was it the best analogy? Perhaps not. It was definitely good enough. Such an analogy may be persuasive only in respect to which property you are observing. In this analogy, that property is toxicity. What about other properties? Is toxicity itself even the best property to focus on?

I believe there are at least two reasons why the alcohol analogy may not be the best analogy.

Ethanol is toxic, albeit to a lesser degree than methanol.

Both ethanol and methanol are highly flammable.

Firstly, Ethanol is indeed toxic. Just ask someone who is drunk and praying to the porcelain god. Moreover, heavy long-term alcohol use is a common cause of cirrhosis.² Granted, compared to ethanol, methanol is drastically more toxic. DO NOT DRINK METHANOL. You will go blind.³ Literally. My discomfort with the alcohol analogy is that it appears to imply that ethanol is as safe to drink as distilled water and has no toxicity at all, which is not accurate. Most skilled artisan parents would likely not give their toddlers shots of 100 proof vodka. Rum perhaps, if they are pirates.

Secondly, both ethanol and methanol are highly flammable. Let’s extend the analogy to even simpler molecules such as ethane (two carbons) and methane (one carbon). Both are also highly flammable. Just ask Blue Origin about their New Glenn Rocket.⁴ Granted, methanol and ethanol indeed have different burn rates depending on various factors such as concentration. However, though the lens of flammability, I think that a provisional application claiming a flammable composition and describing ethanol would likely provide adequate written description support for methanol.

Perhaps a good “magic methyl” analogy might be a better than the alcohol analogy. However, while it might be technically better, it might not be as persuasive the alcohol analogy. I fret that it may be dismissed as pedantic. Kudos to the alcohol analogy. It is simple to understand and impactful. Dare I say elegant? Most people, skilled in the art or not, understand the axiom of whisky good, wood alcohol bad.

“Pfizer unveils its oral SARS-CoV-2 inhibitor” B. Halford, C&EN Global Enterprise 2021 99 (13), 7-7. DOI: 10.1021/cen-09913-scicon3. C&EN, 2021, 99 (13), p 7 April 12, 2021 ↩︎
https://www.mayoclinic.org/diseases-conditions/cirrhosis/symptoms-causes/syc-20351487 ↩︎
P.F. Suit, at al., “Methanol intoxication: clinical features and differential diagnosis” Cleve Clin J Med 1990; 57:464-471 https://www.ccjm.org/content/ccjom/57/5/464.full.pdf ↩︎
https://apnews.com/article/blue-origin-rocket-explosion ↩︎

2 ≠ 1: Enanta v. Pfizer

The U.S. Court of Appeals for the Federal Circuit (CAFC) issued another decision where they held an applicant to a narrow interpretation of one their application’s definitions.

In Enanta Pharmaceuticals. Inc. v. Pfizer Inc., No. 2025-1427 (June 23, 2026), the court held that Enanta’s U.S. Patent No. 11,358,953 (“the ’953 Patent”) could not claim the benefit of priority to U.S. Provisional Patent No. 63/054,048 because the patent’s recitation of “NCH(O)-C₁-C₁₂-alkyl” in its definition of “substituent” could not be supported by the provisional applications disclosure of only “-NCH(O)-C₂-C₁₂-alkyl” in its own definition. Without that priority, Pfizer’s disclosure of a species that falls within the Enanta’s generic claim is invalidating, novelty-defeating prior art.

Timeline:

July 20, 2020: Enanta filed a provisional patent describing a substituent comprising a “C₂-C₁₂ alkyl.”
April 6, 2021: Pfizer disclosed PF-07321332 (nirmatrelvir), which has a “C₁” for the substituent.
November 9, 2021: Enanta filed the non-provisional correcting C₂ to C₁.

Enanta argued that “C₂” was merely a typographical error that a skilled artisan would recognize the error as such and clearly conclude that the inventor was in possession of the full range of “C₂-C₁₂.” The court disagreed saying that the “disclosure of one chemical compound, or integer in this case, cannot necessarily be a disclosure of another, even one close by structurally.” They backed it up with the analogy of “asking whether a disclosure of ethanol, a two-carbon alcohol regularly consumed by people, would provide adequate written description support for methanol, a one-carbon alcohol that is highly toxic to people.”

Fair point. Magic-methyls are indeed real for various properties of certain chemical compounds. However, I think there is more nuance to discuss. I also think there are other lenses that the court could have used to view the facts in this case.

I intend to follow up this post with further analysis of this case.

Check back soon!

Patent Lexicography: When “Branched Alkyl” ≠ “Branched Alkyl” – A Cautionary Tale

Before fancying yourself as your own lexicographer, read the cautionary tale told by the U.S. Court of Appeals for the Federal Circuit’s decision in Alnylam Pharmaceuticals, Inc. v. Moderna, Inc., No. 2023-2357. In this case, the court held Alnylam to their narrow definition of “branched alkyl” instead of its ordinary meaning. The narrow definition allowed Moderna’s COVID-19 vaccine SPIKEVAX® to avoid infringement of Moderna’s patents (U.S. Patent Nos. 11,246,933 and 11,382,979).

Estimated reading time: 2 minutes

Introduction: Conflict between a term’s ordinary meaning and an applicant’s own definition

Generally, words or phrases are given their ordinary and customary meaning in a patent claim. However, an inventor may act as their own lexicographer and define terms inconsistently from the term’s ordinary meaning. While drafting definitions of terms more narrowly than their ordinary meaning may be advantageous at times, such definitions may be disadvantageous if the broader ordinary and customary meaning is needed in litigation.

High Level Summary

In Alnylam’s case, Moderna did not infringe Alnylam’s patents because Alnylam defined its term “Branched Alkyl” too narrowly. The court held Alnylam to its patent definition of “Branched Alkyl” to mean an “alkyl in which one carbon atom in the group (1) is bound to at least three other carbon atoms, and (2) is not a ring atom of a cyclic group,” instead of Alnylam’s later suggested ordinary meaning of “a saturated hydrocarbon moiety that is not a straight chain.” The patent’s definition limited Alnylam’s claims to covering only lipids that comprised tertiary or quaternary carbons. Therefore, Alnylam’s claims could not cover Moderna’s cationic lipid SM-102, which only comprised primary or secondary carbons, as used in SPIKEVAX®.

The court treated the term “Branched Alkyl” as having a binding lexicographic definition because:
(1) the term was located in a “Definitions” section,
(2) the term was in quotation marks,
(3) the definition included the phrase “refers to,” which confers definition intent,
(4) other definitions used non-liming phrases such as “for example” and “including, but not limited to,” and
(5) the definition included the phrase “unless otherwise specified,” which suggests that the rest of the sentence establishes a generally applicable rule or definition.

For further reading, see these other links to blogs discussing Alnylam v. Moderna:

Home

Updated Reference for Protecting Groups

Greene’s Protective Groups in Organic Synthesis, P. G. M. Wuts, 6^thedition, John Wiley & Sons, 2025.
ISBN: 978-1-394-23318-2

Sample description for adding to a patent application specification:
[0001] Nitrogen protecting groups, oxygen protecting groups and sulfur protecting groups are well known in the art and include, but are not limited to, those described in Greene’s Protective Groups in Organic Synthesis, P. G. M. Wuts, 6^thedition, John Wiley & Sons, 2025, incorporated herein by reference.

Caution! Before fancying yourself as your own lexicographer, read the cautionary tale told by the U.S. Court of Appeals for the Federal Circuit’s decision in Alnylam Pharmaceuticals, Inc. v. Moderna, Inc., No. 2023-2357. In this case, the court held Alnylam to their narrow definition of “branched alkyl” instead of its ordinary meaning.
Look out for an more detailed post on the case shortly.

Reference for Pharmaceutical Formulations

It is time to update your draft patent applications with the latest version of Remington.

Remington: The Science and Practice of Pharmacy
23^rd Edition – October 30, 2020
Imprint: Academic Press
Editor: Adeboye Adejare
Language: English
Hardback ISBN: 978-0-12-820007-0

“A thorough discussion of pharmaceutically acceptable excipients is available in Remington: The Science and Practice of Pharmacy, A. Adejare, 23^rd edition, Academic Press, New York, NY, 2020, incorporated herein by reference.”

SCHRÖDINGER’S POLYMORPH: WHEN A CRYSTALLINE FORM CLAIM IS OBVIOUS AND INVALID

Salix Pharmaceuticals, Ltd. v. Norwich Pharmaceuticals Inc., No. 22-2153 (Fed. Cir. 2024)

“Schrödinger’s cat,” is a paradoxical thought experiment devised by physicist Erwin Schrödinger, while debating quantum superposition in 1935. Oversimplified, in the thought experiment, there is a cat in a box, and you have no way of knowing what physical state the cat is in, like a quantum wave function, until you open the box and observe it.

While studying polymorphic forms, like Schrödinger’s hypothetical [albeit a long stretch], you do not know what form a solid compound is until you measure it with x-ray crystallography. However, unlike Schrödinger’s hypothetical, you may have a reasonable expectation of succeeding to figure out what form your compound is depending on the prior art and knowledge of a person of ordinary skill.

Shifting from quantum to organic chemistry patent law, if there is a reasonable expectation of success in characterizing a known crystalline product for potential polymorphism using routine, conventional methods and skill, then a claim to that crystalline product would be invalid for obviousness. Such was the decision in Salix Pharmaceuticals, Ltd. v. Norwich Pharmaceuticals Inc., No. 22-2153 (Fed. Cir. 2024).

Salix claimed a specific crystalline form (form β) of rifaximin. The United States patent and Trademark Office (USPTO) granted Salix a patent on it. However, when litigated, the United States Court of Appeals for the Federal Circuit (CAFC) affirmed the District Court of Delaware’s finding that Salix’s claims to rifaximin form β were invalid for obviousness.*

“The difference between the prior art and the claims is thus effectively nothing more than the performance of routine characterization to identify the polymorphic forms that result from the known Cannata processes.”
Salix Pharmaceuticals, Ltd. v. Norwich Pharmaceuticals Inc., No. 22-2153 (Fed. Cir. 2024), at 15.

In other words, you cannot claim ownership of a compound just by making the expected crystalline form using someone else’s process and taking an x-ray crystal structure of it and giving a Greek letter name.

Background

Salix markets Xifaxan® (rifaximin), and Norwich wanted to sell a generic version.
Xifaxan® is a formulation of rifaximin crystalline form β.
- Polymorph β is a commonly produced polymorph.
- Polymorph β the most stable form of rifaximin.
Disputed patent claims: Claim 4 of U.S. Patent No. 7,612,199 and Claim 36 of U.S. Patent No. 7,902,206.
- Claim 4. Rifaximin in polymorphic form β, wherein the rifaximin has x-ray powder diffraction pattern peaks at about 5.4°; 9.0°; and 20.9°2θ and wherein the rifaximin has a water content of greater than 5%.
Prior art: Cannata et al. U.S. Patent No. 4,557,866.
- Although Cannata does not discuss rifaximin’s crystal structure in detail, it does disclose several preparation protocols for rifaximin that include solvents used for crystallization.
- Experts testified that Cannata’s preparation of crystalline Rifaximin would have yielded its β form. But they could not say it would every time.
Rifaximin was a known compound with a known, useful activity (antibiotic).
- While rifaximin was a known antibiotic, Salix owns rights to patents covering new method of use (hepatic encephalopathy). Salix won on appeal for such method-of-use claims.
Experts testified that Cannata’s preparation of crystalline rifaximin would have easily made and taken an X-Ray diffraction pattern to determine that rifaximin was in its β form.
- The experts could not convince the judge that the prior art process would produce rifaximin form β “every time.” If they could, then Salix’s claims would have been anticipated (not novel) as inherently present in the prior art.^‡
- Although the experts could not convince the judge of the certainty of form β (novelty), they at least convinced the judge that form β was reasonably expected (obviousness).

CAFC Opinion Discussion

The CAFC decided that “the district court found a reasonable expectation of success in characterizing the crystalline product of Cannata for potential polymorphism using routine, conventional methods and skill [Salix Pharm., Ltd. v. Norwich Pharm., Inc., Civil Action No. 20-cv-430-RGA, (D. Del. Apr. 29, 2021), at *6–7].^† We see no clear error in that conclusion. Indeed, Salix has done no more than combine known elements of the prior art to verify readily accessible information concerning a compound already in the hands of those of ordinary skill in the art, and such routine efforts do not justify removing this polymorph from the public domain. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 427 (2007); see also Pfizer, 480 F.3d at 1367−68.”

The District Court supported its factual determinations of obviousness with expert testimony that:

(1) a skilled artisan would have had good reason to characterize the crystalline rifaximin obtained by following the Cannata protocols,

(2) such characterization was routine and could have been performed “in one day,” and

(3) doing so would have led the skilled artisan to have “detected rifaximin β.”

Salix argued that a person of ordinary skill in the art would not have “expect[ed] to succeed” because, as of the critical date, the polymorphic nature of rifaximin had not yet been reported and the identity of the β form remained undisclosed. They further argue that a skilled artisan would not have been able to predict which polymorphic form Cannata made. This argument was flawed. The CAFC states that Salix’s is incorrect in framing of the issue, as it suggests that no unknown entity could ever be obvious, as one cannot reasonably expect what was hitherto unknown.

* In the same appeal, The CAFC did affirm the District Court’s finding that Salix’s other claims to methods of treating hepatic encephalopathy were valid and nonobvious.

† Whether or not there would have been a reasonable expectation of success is a question of fact. “Whether or not there would have been a reasonable expectation of success is a question of fact, (IXI IP, LLC v. Samsung Elecs. Co., 903 F.3d 1257, 1262 (Fed. Cir. 2018)), which we review for clear error, Hospira, 946 F.3d at 1328. We review the ultimate conclusion of obviousness de novo.” Did the Justices themselves believe that the claims were obvious? Unknown. The CAFC perhaps equivocated or sidestepped the question. The justices did not say that they themselves believe that the polymorph claims were obvious. Rather, they merely said that they found no clear error in the District Court’s finding of obviousness.

‡ The CAFC did not opine on whether or not the polymorph claims were invalid for being inherently anticipated (§102). The court said that they did not need to go that far since they already determined that the claims were invalid for obviousness (§103). The district court said that the polymorph claims were not anticipated as being inherent because Norwich did not prove with clear and convincing evidence that the prior art method would produce rifaximin form β “every time.” The inherency issue may deserve its own post. Question for discussion: Does the “every time” requirement go too high for “clear and “convincing evidence?” Perhaps requiring a specific result Every time may go up to the realm of “beyond a reasonable doubt,” which is not the level of burden of proof for patent law. Recall last year’s discussion of the Amgen case where there were arguments about how many examples enable the “full scope” of a claim. Stay tuned.

Additional Information

OrganicPatents.com page on Obviousness of Stereoisomers &Purified Compounds

Obviousness of Stereoisomers & Purified Compounds

May 8, 2024

10-Month Rule: Federally Funded Provisional Patent Applications

File your non-provisional patent application early, within 10 months of filing your provisional application if your invention was conceived using Federal funding.

ISSUE: What might be the consequences for a contractor after failing to timely file a non-provisional patent application within 10 months of filing its provisional patent application?

RULE: The agency can request conveyance of title upon contractor’s omission to timely file patent applications in any country.¹ Timely filing means filing a non-provisional patent application within 10 months of filing a provisional patent application (the “10-Month Rule”).

RULE NEEDS CLARIFICATION: Though the 10-Month Rule may sound straightforward, the rule may conjure further issues. The authority is found in the Federal Regulations at 37 C.F.R. 401.14(c)(3). However, the C.F.R.’s wording may leave matters open for debate.

Unfortunately, guidance from other sources appears to be sparse. The 10-Month Rule is not specifically recited in 35 U.S.C. § 202 and the Federal Statutes that codified the Bayh-Dole Act. Furthermore, the manual of Manual of Patent Examining Procedure (MPEP) does not appear to refer to the 10-Month Rule. Furthermore, there does not appear to be any case law opining on the 10-Month Rule.² This is likely because no Federal Agency has yet to enforce the 10-Month Rule, analogously to how no Federal Agency to-date has not activated any march-in-rights they may have under the Bayh-Dole Act. At least no litigation has arisen after an enforcement of the 10-Month Rule.

ISSUES FOR CLARIFICATION:

Timing?

QUESTION: When can the Federal agency request conveyance of title? The question may be further split up into two questions of when:

(1) From what time?; and

(2) Until what time?

ANALYSIS (1): The C.F.R. clearly shows that the Federal agency may request conveyance of title from the time the contractor fails to timely file its non-provisional application. This means that the Federal agency may request conveyance of title after the 10-month deadline if the contractor has not yet filed its non-provisional patent application.

ANALYSIS (2): The C.F.R. does not provide clear guidance. The Federal agency clearly my request title from at least 10 months to 12 months (i.e., the Statutory deadline to file in the US/PCT). But the Federal agency may not clearly continue to have the right to request conveyance after 12 months, even if the contractor filed its non-provisional application in compliance with the statutory 12-months anyway.

DISCUSSION:

The 10-Month Rule makes sense under the scenario where a contractor has not filed the non-provisional and the time is now 11-months from the contractor’s provisional application filing date. In this scenario, I can see the Federal agency saying: “You did not file it after 10-months, it is now 11-months. This invention is ours now. We are going to file it ourselves and own it 100% now. And by the way, you are not getting it back.”

What I believe may remain ambiguous, is whether or not the federal agency can still require conveyance of resulting non-provisional application even if the non-provisional application was filed anyway, after 10 months, yet before 12 months. One could argue that, yes, the Federal agency can, at any time over the next 20 years, take the patent away from the contractor. That would be cruel. However, while I believe that Federal agencies such as the NIH would not be so cruel,³ perhaps a potential infringer might indeed be so cruel to a patent owner by asking a court to rule that the patent owner forfeited its rights to the NIH, long after a patent is granted. A countering argument is that, no, federal agencies cannot do so, because that was not what the rules intended.

Patent Validity and Enforceability

QUESTION:

Is a patent valid and enforceable if it resulted from an non-provisional application that was filed after 10 months of the provisional application, yet filed before the statutory 12 months?

ANALYSIS:

There should not be any challenges to the enforceability or the validity of such a patent because it complied with a Federal Statute, even though it may not have complied with a Federal Regulation.
- This would be contrary to the intent of the Federal Regulations, which appear to have been intended to support the policy of keeping patent applications alive rather than letting them lapse and go abandoned.
The Federal Agency would not want the resulting non-provisional application or patent to be then held invalid or unenforceable. The 10-Month Rule is in place to ensure that a Federal Agency may rescue an invention after a contractor fails to file a non-provisional application after 10 months. The reason for the rule being 10 months is to allow the Federal agency to wrestle control (ownership) of the invention and still have 2 months of time to file the non-provisional application by itself, after the contractor neglected to do so.

See, https://www.nist.gov/tpo/bayh-dole-act/2018-faqs. See also, https://www.fenwick.com/insights/publications/avoiding-loss-of-title-to-inventions-m[…]al-funding-as-new-bayh-dole-requirements-affect-patent-rights – Fenwick & West, LLP. ↩︎
I checked Westlaw & Lexis at the Worcester Law Library. But I may be rusty. ↩︎
Disclosure: I received a Post-Doctoral Research Grant from the NIH in 2000. ↩︎

Inherency & Therapeutic Mechanisms: Reviewing In re Couvaras – (With No-Frills Diagrams)

Q: When can you patent a composition’s mechanism of action?

A: When the mechanism is not inherent in a known use of the composition.

“Reciting the mechanism for known compounds to yield a known result cannot overcome a prima facie case of obviousness, even if the nature of that mechanism is unexpected.”
In re Couvaras, 22-1489 (Fed. Cir., 2023)

In re Couvaras, 22-1489, 2023 WL 3984753 (Fed. Cir., June 14, 2023)

Precedential Opinion by Circuit Judge Lourie; joined by Circuit Judges Lourie, Dyk, and Stoll

The United States Court of Appeals for the Federal Circuit (CAFC) agreed with the Patent Trial & Appeals Board (PTAB), and the USPTO examiner, that claims in U.S. Patent Application No. 15/131,442 (US2016/228,393), which recites methods of increasing prostacyclin release in the systemic blood vessels of a human with essential hypertension to improve vasodilation, were obvious because the claims relate to combatting hypertension with known antihypertensive agents and merely disclose their previously unappreciated mechanism of action.”

High Level Summary

The prior art taught that GABA-a agonists and ARBs reduce anti-hypertension. Dr. Couvaras discovered that GABA-a agonists and ARBs reduce anti-hypertension, in part, because they increase prostacyclin and promote vasodilation. Dr. Couvaras applied for a patent claiming a method of increasing prostacyclin in an individual with hypertension to improve vasodilation by providing an ARB and a GABA-a agonist. However, the USPTO rejected the claims because the element of increasing prostacyclin was inherent in the well-known prior art method of independently treating hypertension with an ARB or a GABA-a agonist.

Visualizing the case with diagrams

Now let’s skeletonize the elements of this case down to arrow diagrams. We don’t need too many facts getting in the way of this good story. 🙂 *

Claim 11 (abridged): A method of increasing prostacyclin in an individual with hypertension to improve vasodilation by providing an ARB and a GABA-a agonist.

A = Providing an ARB and a GABA-a agonist

X = Increasing prostacyclin

B = Vasodilation (treating hypertension)

* But seriously, although I am scientist reluctant to loose any nuance, technical terms such as Angiotensin II Receptor Blocker (“ARB”) can be distracting in analyzing the the law in case. Also, I believe that knowing the claims recite a combination therapy is superfluous and thereby distracting itself. (At least I found them distracting at first. Maybe that’s just me. Please work with me for now.) The CAFC’s rule of law works for both mono and combo therapies. See below for a discussion regarding combination therapies.

The overall goal is to get from A to B. Doctors already know how to get from A to B. It is prior art. No argument there. Then an inventor discovers that X is the mechanism of action that leads to B.

Doctors did not already know that going from A to B involves X. This is not taught in the prior art. A→X is a genuine new discovery. No argument there either.

Now you have A→ X→ B.

Although the discovery of A→ X is indeed new, inventors should not be able to patent a claim to the discovery. Even though doctors did not know it, doctors were inherently doing the process of A→ X→ B by simply prescribing A to treat B. It makes sense that someone should not be able to patent a claim to A→ X→ B, or even simply A→X, then suddenly prevent doctors from prescribing A→ B, which they have been doing all along.

New methods and mechanisms of action may still be patented

In re Couvaras, however, does not mean that all mechanisms and new uses are not patentable. New uses for old compounds May still be patentable. For example, an inventor may discover that A also renders the benefit of C, and that A affects B by going through mechanism Y.

In this example, the inventor may be able to patent a claim to A→C.

If an inventor simultaneously discovers that A→C goes through the mechanism “Y” then they may be able to patent a claim covering both A→C, A→Y, and A→Y→C.

NOTE: The inventor should file both claims simultaneously so the inventor’s disclosure of A→C does not block the claim to A→Y. If not, then the inventor will have the same problem from In re Couvaras.

In summary, patentability of mechanisms (X/Y) rest on the whether the overall benefit (B/C) is unexpected from the known composition (A).

Secondary Considerations

Of course, secondary considerations provide some leniency. But the secondary considerations surely need to be compelling.

“To establish unexpected results, Couvaras would have needed to show that the co-administration of GABA-s agonist and an ARB provided an unexpected benefit,” such as, e.g., better control of hypertension or less toxicity.

Failure of others: “The purported failure to achieve prostacyclin increase through pursuing an unrelated goal did not establish the non-obviousness of the claimed method.”

No long felt need: The anti-hypertensive agents were admitted to be available already.

“The pending claims of the ’422 application literally recite methods of increasing prostacyclin release in the systemic blood vessels of a human with essential hypertension to improve vasodilation. That increased prostacyclin release is achieved by co-administering two well-known types of antihypertensive agents: a GABA-a agonist and an Angiotensin II Receptor Blocker (“ARB”). In reality, the claims relate to combatting hypertension with known antihypertensive agents and claiming their previously unappreciated mechanism of action.”

Novelty vs. Obviousness: Inherency

Q: Why is inherency in a case about obviousness and not about novelty?

A: Here is where the combo-therapy aspect comes in. A combination of two known compounds that render the same benefit is obvious. Dr. Couvaras argued that the discovery of the compounds’ mechanism of action overcame the obviousness rejection. Essentially the argument tried to convince the examiner that each mono therapy was novel. With two novel monotherapies in hand, reasoning follows that combination of two novel monotherapies would have been non-obvious.

Post Script

On bright side, The USPTO awarded Dr. Couvaras with U.S. Patent No. 9,339,542 in his earlier application. Composition claims to combinations were non-obvious.

Granted Claim 1: A composition effective to relax Smooth muscles in an individual in an altered state, the composition comprising: a dosage of GABA or GABA-a analogue; and a dosage of at least one of an ACE inhibitor and a ARB combined with the dosage of GABA or GABA-a analogue into a deliverable form.

Small Molecule Lens for Viewing Amgen v. Sanofi

The U.S. Supreme Court’s opinion in Amgen v. Sanofi (No. 21–757, Decided May 18, 2023) was indeed a big deal. From a small molecule chemistry perspective however, I do not believe that the Amgen decision will alter chemical patent prosecution practice regarding enablement law. True, applications may need even more examples to enable small molecule genus claims. But providing enough examples to enable claims has always been a challenge. And we have been already progressively honing our strategy likewise along with the USPTO’s progressively stringent requirements. Meanwhile, patent practitioners typically do not describe small molecules in functional terms anyway.

Imagine Amgen’s claim 1 of U.S. 8,829,165 (the ’165 patent) being written for a small molecule.

1. A small molecule that binds to PCSK9, wherein the small molecule binds an epitope on PCSK9 comprising at least one of residues 237 or 238 of SEQ ID NO: 3, and wherein the small molecule blocks binding of PCSK9 to LDLR.

I am confident that most chemical patent agents and attorneys would expect such a claim to fail as not enabled. No quantity of exemplary compounds can enable the full scope of covering any small molecule.

Idenix v. Gilead

Regarding enablement of small molecules, the law still stands from the Federal Circuit’s decision in Idenix Pharmaceuticals LLC v. Gilead Sciences Inc. (Fed. Cir. 2019); 941 F.3d 1149 (2018 WL 922125). Prior to Amgen, the U.S. Supreme Court refused to hear Idenix’s appeal [cert. denied, 141 S. Ct. 1234 (2021) No. 20-380].

Please see my earlier post: Idenix v. Gilead: Split CAFC Panel at Least Agrees – Valid or Not, Either Way it’s Idenix Loss – Claims Too Broad.

Recall in Idenix, all three justices– including Justice Newman – agreed that Idenix did not enable the claims with regard to the claim’s infringed elements. Justice Newman disagreed, however, with the majority’s ruling that the claims were invalid. Instead, she argued that the claims should have been ruled to be unenforceable over the infringing product rather than be draconianly ruled as invalid as a whole. I would tend to agree with Justice Newman. Idenix should be at least able to enforce their claims on some other competing product that would be covered by the enabled embodiments. However, I would tend agree with the majority if there were a broad claim to any small molecule defined by functionality alone, without a structure. I don’t believe such a claim should be valid, if not for enablement, perhaps for insufficient written description requirement.

Idenix claimed a method for the treatment of a hepatitis C virus infection by administering an effective amount of a purine or pyrimidine β-D-2′-methyl-ribofuranosyl nucleoside or a phosphate thereof. However, none of their examples included a 2′-methyl “up” / 2’- fluoro “down” analog like Gilead’s sofosbuvir (Solvadi®). Rather, most examples showed 2′-methyl “up” / 2’- hydroxyl “down” analogs.

As Justice Gorsuch opined, “in some cases, disclosing that general quality may reliably enable a person skilled in the art to make and use all of what is claimed, not merely a subset.” Channeling SCOTUS’s preference for seeing a common-quality within the claims, the common quality for Idenix would probably have been the 2’- fluoro “down” element, and not just the broad 2′-methyl element.

Even prior to Amgen, chemical patent practitioners have been keen to include so-called common qualities in core aspects of generic structure formulas. Skilled patent practitioners draft intermediate and narrow sub-generic formulas for embodiments in case broad generic formulas are challenged. Such intermediate formulas often surround a preferred set of species. The preferred set of species often have a common quality that may make them more active or stable than other series of compounds. Seek out your favorite medicinal chemist. They can explain it better than I can.

Examples

For example, a patent application may include a generic formula that recites the broad term “aromatic group.” Meanwhile, the patent application should also include backup provisions such as a sub-generic formula that narrows the term “aromatic” to “heteroaromatic.” Furthermore, the application should include an even narrower backup embodiment wherein the “heterocyclic group can be a specific heterocycle such as pyridine, pyrimidine or pyrazine. The scope of the generic formula would be guided by the compounds exemplified in the application.

In one hypothetical scenario, a claim to any aromatic group may fail if only heteroaromatic groups are shown in examples. In a further scenario, a claim to a heteroaromatic group may fail if only pyridines are exemplified. Perhaps pyrimidines or pyrazines, with two nitrogens, may have significantly different functional properties than a pyridine having only one nitrogen.

As before Amgen v. Sanofi, a greater variety of exemplary compounds provides a stronger argument for enablement.

[ I intend to add more discussion soon. Check back. Thank you for reading! ]

Amgen Throws Patent Attorneys Under Bus

“Chemists would not routinely rely on the statements of patent lawyers.”

Amgen v. Sandoz, 22-1147 (CAFC, 2023)

Please pardon my delay in posting. I needed to check my wall to see if my diploma was still hanging there. Yes, it is still there. Like many of my fellow patent attorneys, I have a PhD in chemistry. Being a patent attorney and a chemist is not mutually exclusive. To be fair, my laboratory technique might be quite rusty after 20 years behind a desk. But I still consider myself 100% a chemist.

Twice, Amgen’s litigators successfully argued that Amgen’s own patent prosecutors were wrong and should be ignored. First, Amgen persuaded the court to ignore disclosure in the patent application specification regarding purification processes using crystallization. Second, Amgen persuaded the court to ignore statements that their European Council made to the European Patent Office (EPO) regarding which products resulting from Example 2 of Amgen’s U.S. Provisional Application 60/366,515.

Patent attorneys often worry about potential adverse statements that anybody makes during prosecution of patent applications. Keep statements and arguments minimal because, once in writing, you cannot take them back. This case appears to be a rare exception. Depending on whose side you’re on, perhaps it is refreshing that cases such as this show that potentially detrimental statements may be ignored once in a while provided the right evidence.

Otezla® (apremilast) ANDA litigation

Background

Apremalist is an optically pure dextrorotary “(+)” enantiomer of 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, having its
stereo center in the “S” conformation. Stereoisomers regarding apremalist are a big deal because of their similarities to thalidomide.

The dispute arose from Sandoz’s filing an Abbreviated New Drug Application (ANDA) to sell a generic version of Amgen’s Otezla® (apremalist), a PDE-4 inhibitor used for treating psoriasis.

Amgen then sued Sandoz to enforce, among others, U S. Patent 7,427,638 claiming a pharmaceutical composition comprising the (+) enantiomer, and U.S. Patent 10,092,541 claims a crystalline solid form of the (+) enantiomer (Form B).

There were several other issues in this opinion. One that I have spent much time considering is the issue of patenting of stereoisomers. Look out for my subsequent post to the page “Obviousness of Stereoisomers & Purified Compounds” regarding the decision in this case.

Priority Claim

U S. Patent 7,893,101 claims priority to earlier provisional patent application 60/366,515. Sandoz argued that the priority claim was invalid because Example 2 in the provisional application, instead of making only crystalline Form B, also made Form C. Sandoz cited as evidence Amgen patent council’s statements to the EPO stating that Example 2 made both forms. However, counsel’s statement was wrong because Example 2 indeed only made Form B. Amgen was allowed to present data to prove it, including thirteen third-party experiments. With the data as evidence, Amgen was able to take back their erroneous, detrimental statement.

Non-Obviousness

Sandoz argued that Amgen’s claims to optically pure compound were obvious because statements in the specification about the separation of the enantiomers. The Statements made the process of isolating enantiomers sound routine. However, Amgen was able to persuade the court that isolating the (+) enantiomer was not routine because, contrary to the specification, formation of chiral salts was not viable. In other words, oversimplified colloquially, the patent attorney drafting the application made the invention sound too easy describing techniques that real chemists would know actually would not work.