Details for Patent: 11,351,149

Which drugs does patent 11,351,149 protect, and when does it expire?

Patent 11,351,149 protects PAXLOVID (COPACKAGED) and is included in one NDA.

This patent has seventy-five patent family members in thirty-eight countries.

Summary for Patent: 11,351,149

Title:	Nitrile-containing antiviral compounds
Abstract:	The invention relates to compounds of Formula I″wherein R, R1, R2, R3, p, q and q′ are as defined herein, pharmaceutical compositions comprising the compounds, methods of treating coronavirus infection such as COVID-19 in a patient by administering therapeutically effective amounts of the compounds, and methods of inhibiting or preventing replication of coronaviruses such as SARS-CoV-2 with the compounds.
Inventor(s):	Dafydd Rhys Owen, Martin Youngjin Pettersson, Matthew Richard Reese, Matthew Forrest Sammons, Jamison Bryce Tuttle, Patrick Robert Verhoest, Liuqing Wei, Qingyi YANG, Xiaojing Yang
Assignee:	Pfizer Inc
Application Number:	US17/395,139
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,351,149
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 11,351,149: Nirmatrelvir Crystal Forms, Composition Claims, and Patent Landscape

US Patent 11,351,149 protects nirmatrelvir, the active antiviral component of Paxlovid, in multiple physical forms, including crystalline Forms 1, 2 and 4, amorphous material, methyl tert-butyl ether solvates, compositions, and coronavirus-treatment methods. The patent is a solid-form and product-use patent rather than a broad manufacturing-process patent. Its strongest commercial value is the ability to constrain manufacture and formulation of the same nirmatrelvir solid form used in an approved product.

The patent does not cover ritonavir, the pharmacokinetic booster co-packaged with nirmatrelvir in Paxlovid. It also does not create biologic exclusivity. Competitive entry would proceed through the small-molecule generic pathway, principally an ANDA with Paragraph IV certifications where applicable.

What compound does US Patent 11,351,149 protect?

The claimed compound is nirmatrelvir, also known as PF-07321332, a SARS-CoV-2 main protease, or 3CL protease, inhibitor developed by Pfizer.

The chemical name recited in the claims is:

(1R,2S,5S)-N-{(1S)-1-Cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide.

The compound contains the structural elements associated with nirmatrelvir:

• A nitrile warhead that covalently interacts with the catalytic cysteine of coronavirus main protease.
• A bicyclic proline-derived core.
• A trifluoroacetyl-protected tert-leucine-like side chain.
• A 2-oxopyrrolidine substituent.
• Defined stereochemistry at multiple chiral centers.

The claims cover the compound itself, subject to the specific structure shown in the patent, and include solvates and hydrates in claim 1.

How are the 26 claims organized?

The claims divide into five principal categories.

Claim group	Claims	Subject matter
Compound and solvates	1, 22	Nirmatrelvir, including solvates or hydrates in claim 1
Crystalline and amorphous forms	2-10	Crystalline nirmatrelvir, Solid Forms 1, 2 and 4, amorphous material and MTBE solvate
Pharmaceutical compositions	11, 14-17, 23, 25-26	Compositions containing nirmatrelvir or specified solid forms
Coronavirus treatment	12-13, 18-21, 24	Administration of nirmatrelvir for coronavirus infection and COVID-19
Structural-form repetitions	22-26	Repetition of compound, composition and method claims with structural depictions or solid-form limitations

Claims 1, 11 and 12 are the principal broad claim categories:

• Claim 1 covers the defined nirmatrelvir molecule and its solvate or hydrate.
• Claim 11 covers a pharmaceutical composition containing the molecule and a pharmaceutically acceptable carrier.
• Claim 12 covers treatment of coronavirus infection by administering a therapeutically effective amount.

The later claims narrow those categories by adding solid-state, crystal-form or disease-specific limitations.

What crystalline forms are protected by US Patent 11,351,149?

The patent protects at least three named solid forms and amorphous nirmatrelvir.

Solid Form 1

Claims 3, 4, 15, 19 and 25 cover Solid Form 1. The claim set identifies Solid Form 1 using:

• A powder X-ray diffraction pattern corresponding to Figure 3.
• A listed series of diffraction peaks, generally within ±0.2 degrees two theta.
• A solid-state fluorine-19 NMR peak at -73.3 ± 0.1 ppm.
• Solid-state carbon-13 NMR peaks at 31.0 ± 0.1 ppm, 27.9 ± 0.1 ppm and 178.9 ± 0.2 ppm.

Solid Form 1 is important because it is defined through analytical identity rather than solely through the chemical structure. A generic product containing the same molecular compound could avoid a literal solid-form claim only if its material did not meet the claimed PXRD or NMR limitations and did not otherwise fall within an independent compound or composition claim.

Solid Form 4

Claims 5, 6, 16, 20 and 26 cover Solid Form 4. The claim identifies the form through:

• A powder X-ray diffraction pattern corresponding to Figure 6.
• Multiple peaks between approximately 7.6 and 39.8 degrees two theta.
• Solid-state fluorine-19 NMR at -73.6 ± 0.1 ppm.
• Selected carbon-13 NMR peaks at 26.9 ± 0.1 ppm, 21.6 ± 0.1 ppm and 41.5 ± 0.1 ppm.

Claim 5 uses an unusual formulation, stating that each peak is “+0.2 degrees two theta.” That wording is narrower and potentially more vulnerable to claim-construction disputes than the more conventional “±0.2” formulation. The enforceability of that limitation would depend on the prosecution history, specification, and whether the court treats the language as a drafting error or an intentional unilateral tolerance.

Methyl tert-butyl ether solvate, Solid Form 2

Claims 8-10 protect nirmatrelvir methyl tert-butyl ether solvate and its crystalline Solid Form 2. Claim 10 defines the form by a PXRD pattern corresponding to Figure 1 and a list of diffraction peaks.

This is a process-relevant claim category. MTBE solvates can arise during crystallization or isolation. A manufacturer using MTBE in a route could produce an intermediate or final material that falls within the solvate claims, even if the marketed product is subsequently desolvated. The legal risk depends on whether the commercial process makes, uses, imports or sells the claimed solvate and whether the final product retains the claimed form.

Amorphous nirmatrelvir

Claim 7 covers amorphous nirmatrelvir. Claims 17 and 21 extend the amorphous limitation into composition and treatment claims.

Amorphous material normally has no long-range crystal lattice and therefore may not meet the PXRD limitations for Forms 1, 2 or 4. It remains potentially covered by the broader compound claim, the amorphous claim, or the composition and method claims.

What is the scope of the composition claims?

Claim 11 covers a pharmaceutical composition containing nirmatrelvir, including a solvate or hydrate, together with a pharmaceutically acceptable carrier.

The claim does not specify:

• A particular dosage strength.
• A particular tablet or capsule design.
• A particular excipient.
• A particular nirmatrelvir-to-ritonavir ratio.
• A particular release profile.
• A particular manufacturing process.

Claims 14-17 and 23, 25 and 26 narrow the composition to crystalline material, amorphous material, Solid Form 1 or Solid Form 4.

The composition claims could therefore reach a generic tablet or capsule if the dosage form contains the claimed nirmatrelvir material and otherwise satisfies the claim elements. A formulation that changes excipients would not necessarily avoid the claims because claim 11 requires only a pharmaceutically acceptable carrier.

The supplied claims do not expressly recite ritonavir. A Paxlovid-like co-packaged product could implicate the patent through the nirmatrelvir component even though ritonavir is outside the claimed chemical subject matter.

What method-of-use protection does the patent provide?

Claims 12 and 13 cover treatment of coronavirus infection, with claim 13 expressly identifying COVID-19. Claims 18-21 narrow those methods to crystalline, Solid Form 1, Solid Form 4 or amorphous nirmatrelvir.

The method claims require:

1. A patient in need of treatment.
2. A coronavirus infection.
3. Administration of a therapeutically effective amount.
4. The claimed nirmatrelvir compound or specified physical form.

These claims are narrower than a general antiviral-use claim because they are tied to the defined nirmatrelvir structure. Claim 13 is commercially significant because it expressly covers COVID-19 treatment, the indication associated with Paxlovid.

Method-of-use claims can create ANDA risk even when a generic applicant does not seek approval for every patented indication. Under the Hatch-Waxman framework, a generic applicant may use a section viii statement to carve out a patented method of use if the proposed label can omit that indication. A carve-out is less effective where the proposed label, promotional materials or product use would still encourage the patented treatment.

When does US Patent 11,351,149 lose exclusivity?

The nominal patent term is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers and any applicable patent-term extension. A reliable expiration date cannot be calculated from the claims alone.

For a commercial freedom-to-operate analysis, the relevant date must be taken from:

• The patent front page.
• USPTO Patent Center.
• The continuity and priority statements.
• The patent-term adjustment calculation.
• Any terminal disclaimer.
• Any regulatory patent-term extension.

The issuance date, June 7, 2022, does not determine expiration. Nor does the FDA approval date of Paxlovid determine patent expiration.

FDA granted Paxlovid an Emergency Use Authorization in December 2021 and later approved it for eligible adults at high risk of progression to severe COVID-19. FDA approval creates regulatory exclusivity and Orange Book consequences, but those periods are separate from the patent term.[1][2]

What is the Orange Book status of nirmatrelvir and Paxlovid?

Paxlovid is a small-molecule prescription product, not a biologic. Its relevant FDA pathway is an NDA, not a BLA. Any listed patents would appear in the FDA Orange Book under the approved product and NDA, subject to FDA listing rules.[3]

The claims supplied do not establish whether US 11,351,149 is currently listed in the Orange Book, whether it was listed at approval, or whether any listing has been delisted or challenged. Patent issuance alone does not prove Orange Book listing.

The regulatory structure is:

Issue	Relevance to US 11,351,149
Product	Paxlovid
Active antiviral	Nirmatrelvir
Booster	Ritonavir
FDA pathway	NDA
Generic pathway	ANDA
Biosimilar pathway	Not applicable
Potential certification	Paragraph IV if an applicable listed patent is challenged
Method-of-use carve-out	Potentially available under section viii, depending on the approved label

FDA’s Orange Book identifies patents submitted by NDA sponsors, but it does not resolve infringement, validity or enforceability.[3]

Which patents compete with or surround US Patent 11,351,149?

The nirmatrelvir estate is expected to include several patent families with different technical functions.

Core compound patents

Core compound families cover nirmatrelvir and related coronavirus protease inhibitors. These patents generally present the highest blocking risk because they may reach the active pharmaceutical ingredient regardless of crystal form.

Solid-form patents

US 11,351,149 is principally in this category. It protects:

• Specific polymorphs.
• Amorphous nirmatrelvir.
• An MTBE solvate.
• Solid-state analytical signatures.
• Compositions and treatments using those materials.

Formulation patents

A separate formulation family could cover tablets, co-formulations, dosage ratios, coatings, excipients, stability systems or packaging. The claims supplied here do not recite a specific formulation architecture and should not be treated as a complete Paxlovid formulation estate.

Manufacturing patents

Process patents may cover:

• Preparation of chiral intermediates.
• Formation of the nitrile-containing warhead.
• Peptide coupling.
• Protection and deprotection steps.
• Crystallization and solvent exchange.
• Control of residual solvent and polymorphic conversion.

US 11,351,149 creates a manufacturing barrier where a process produces a claimed polymorph or MTBE solvate. It does not, based on the supplied claims, claim the synthetic route itself.

Combination and treatment patents

Method claims may cover nirmatrelvir with ritonavir, dosing schedules, patient populations or treatment windows. The supplied claims cover coronavirus infection and COVID-19 but do not expressly require ritonavir.

How strong is the patent estate?

The patent has meaningful layered protection, but the claims have different enforcement strength.

Claim type	Relative commercial strength	Principal issue
Claim 1 compound/solvate	High if valid and unexpired	Broad chemical identity and possible overlap with earlier compound patents
Claims 3-6 solid forms	High against matching polymorphs	Analytical proof, polymorph identity and claim construction
Claims 7-10 amorphous and MTBE solvate	Moderate to high	Whether commercial material contains the claimed state or solvate
Claim 11 composition	Moderate	Requires presence of claimed compound in a pharmaceutical composition
Claims 12-13 treatment	Moderate	Label scope, induced infringement and section viii carve-out
Claims 14-26 dependent claims	Narrower	More limitations create design-around and non-infringement opportunities

The strongest practical protection comes from the combination of compound, solid-form and composition claims. A generic manufacturer must avoid more than one risk layer: the active molecule may be covered by a core compound patent, while the selected polymorph may be covered by US 11,351,149 and the marketed dosage form may be covered by a separate formulation patent.

What generic launch scenarios exist?

Scenario 1: Paragraph IV challenge

A generic applicant may certify that a listed patent is invalid, unenforceable or not infringed. The NDA holder may file patent litigation within the statutory period, potentially triggering a 30-month stay of final ANDA approval under Hatch-Waxman.[4]

For US 11,351,149, likely challenge theories could include:

• Anticipation by an earlier disclosure of nirmatrelvir or the same solid form.
• Obviousness based on known protease inhibitors and polymorph-screening techniques.
• Lack of written description for the full scope of solvates, hydrates or amorphous material.
• Lack of enablement for all claimed forms.
• Indefiniteness of PXRD tolerance language.
• Non-infringement because the generic uses a different polymorph or amorphous state.

Scenario 2: Paragraph III certification

A generic applicant may accept the patent and defer approval until expiration. This avoids immediate validity litigation but preserves the patent as a timing barrier.

Scenario 3: Section viii carve-out

A generic label may omit the COVID-19 indication if the relevant patent is listed only for a method of use and the FDA accepts the carve-out. This approach does not avoid compound or composition claims.

Scenario 4: Different polymorph or formulation

A manufacturer may attempt to use a non-claimed polymorph, a controlled amorphous dispersion or a different solvate. That strategy requires analytical evidence because processing can cause conversion between forms during milling, granulation, drying, storage or tableting.

What patent litigation and settlements affect nirmatrelvir entry?

The claim text does not identify litigation, Paragraph IV notices or settlement agreements. Those matters cannot be inferred from the patent claims.

For diligence purposes, the relevant records are:

• PACER district-court complaints and judgments.
• USPTO Patent Center prosecution history.
• FDA Orange Book patent listings.
• ANDA litigation docket entries.
• FDA exclusivity and approval records.
• Public license or access agreements involving Pfizer, the Medicines Patent Pool or authorized manufacturers.

Pfizer entered into a Medicines Patent Pool agreement relating to certain COVID-19 antivirals, permitting qualified manufacturers to supply nirmatrelvir/ritonavir to specified lower- and middle-income countries under defined conditions.[5] That licensing arrangement does not itself establish freedom to operate in the United States and does not eliminate US patent rights.

What is the geographic coverage?

US 11,351,149 is a United States patent. Its direct exclusionary rights are limited to US manufacture, use, sale, offer for sale and importation under US patent law.

Equivalent protection may exist in other jurisdictions through related national-phase applications or separately granted patents. Geographic risk must be assessed country by country because:

• Claim scope can differ.
• Patent term can differ.
• Examination outcomes can differ.
• Regulatory patent linkage is not uniform.
• Compulsory licensing and public-health provisions differ.
• Patent opposition or revocation proceedings may affect foreign rights.

The United States patent cannot be used as evidence that a corresponding foreign patent is granted, valid or enforceable.

Key Takeaways

• US 11,351,149 is a nirmatrelvir solid-form patent associated with Paxlovid.
• Claim 1 covers the defined nirmatrelvir compound and solvate or hydrate forms.
• Claims 3-10 protect Solid Forms 1, 2 and 4, amorphous material and an MTBE solvate.
• Claims 11-26 extend protection to compositions and coronavirus, including COVID-19, treatment methods.
• The patent does not claim ritonavir or a specific Paxlovid formulation in the supplied claims.
• Generic competition would use the ANDA pathway, not the biosimilar pathway.
• Paragraph IV, Paragraph III and section viii strategies present different launch routes.
• Solid-form claims can be commercially important because manufacturing, drying, storage and tableting can determine infringement.
• The patent’s exact expiration, Orange Book status, litigation history and settlement position require official patent and FDA records rather than claim-text analysis.

FAQs

Does US Patent 11,351,149 cover Paxlovid itself?

It covers nirmatrelvir-related compounds, solid forms, compositions and COVID-19 treatment methods. The supplied claims do not expressly claim ritonavir or the complete two-drug Paxlovid product.

Can a generic avoid this patent by using amorphous nirmatrelvir?

Not necessarily. Claim 7 expressly covers amorphous nirmatrelvir, and claims 17 and 21 extend that limitation to compositions and treatment methods. A generic would also need to assess broader compound and composition claims.

Does the patent cover every nirmatrelvir polymorph?

The claims cover the compound broadly in claim 1 and specifically identify Forms 1, 2 and 4. They do not, based on the supplied text, expressly identify every possible future polymorph.

Can a generic manufacturer use a different solvent to avoid the MTBE solvate claims?

A different solvent may avoid the specific MTBE-solvate limitation, but it would not automatically avoid the compound, amorphous, crystalline, composition or method claims. The final material and manufacturing intermediates require separate analysis.

Is a biosimilar challenge available for Paxlovid?

No. Paxlovid is a small-molecule drug approved under an NDA. A competing product would generally use the ANDA pathway, with patent certifications and possible Hatch-Waxman litigation.

References

1. U.S. Food and Drug Administration. (2021). FDA authorizes first oral antiviral for treatment of COVID-19.
2. U.S. Food and Drug Administration. (2023). FDA approves first oral antiviral treatment for COVID-19 in adults.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. U.S. Code. (2023). 21 U.S.C. § 355(j): Abbreviated applications for new drugs.
5. Medicines Patent Pool. (2022). MPP and Pfizer sign licensing agreement for COVID-19 oral treatment candidate.
6. U.S. Patent and Trademark Office. (2022). U.S. Patent No. 11,351,149, crystalline forms of nirmatrelvir-related compound.

Drugs Protected by US Patent 11,351,149

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Pfizer	PAXLOVID (COPACKAGED)	nirmatrelvir; ritonavir	TABLET;ORAL	217188-001	May 25, 2023		RX	Yes	Yes	11,351,149		Y	Y		TREATMENT OF MILD-TO-MODERATE CORONAVIRUS DISEASE 2019 (COVID-19) IN ADULTS WHO ARE AT HIGH RISK FOR PROGRESSION TO SEVERE COVID-19, INCLUDING HOSPITALIZATION OR DEATH

International Family Members for US Patent 11,351,149

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	123111
Argentina	128528
Australia	2021266232
Australia	2022202158
Australia	2022221493
Brazil	112021022419