Details for Patent: 9,303,051
Which drugs does patent 9,303,051 protect, and when does it expire?
Patent 9,303,051 protects TEMBEXA and is included in two NDAs.
This patent has nineteen patent family members in ten countries.
Summary for Patent: 9,303,051
| Title: | Phosphonate ester derivatives and methods of synthesis thereof | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | The disclosure describes methods of synthesis of phosphonate ester derivatives. Preferred methods according to the disclosure allow for large-scale preparation of phosphonate ester compounds having high purity. In some embodiments, preferred methods according to the disclosure also allow for the preparation of phosphonate ester derivatives without the use of chromatographic purification methods and in better yield than previously used methods for preparing such compounds. Also disclosed are morphic forms of phosphonate ester derivatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Roy W. Ware, Merrick R. Almond, Bernhard M. Lampert | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | Emergent Biodefense Operations Lansing Inc | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US14/808,388 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Patent Claim Types: see list of patent claims | Use; Composition; | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | United States Patent 9,303,051: Brincidofovir Morphic Form B Claims, Patent Scope, and Exclusivity LandscapeU.S. Patent No. 9,303,051 protects Morphic Form B of brincidofovir, the hexadecyloxypropyl ester of cidofovir, through crystal-form claims defined by powder X-ray diffraction peaks. The patent also contains composition and antiviral-treatment claims requiring Morphic Form B. Its principal commercial relevance is Tembexa, the FDA-approved oral antiviral for smallpox. The strongest claim is claim 1, which requires both the specific brincidofovir molecular structure and the claimed crystalline form. Claims 2 through 6 narrow the XRPD characterization. Claims 7 and 8 extend protection to pharmaceutical compositions and treatment methods, while claim 9 identifies covered viral infections. Based on the patent family and FDA product records, the patent has a nominal term extending into 2030, subject to the controlling USPTO term calculation, patent-term adjustment, and any applicable regulatory extensions. Tembexa also received FDA orphan-drug exclusivity separate from patent protection. What drug does U.S. Patent 9,303,051 protect?U.S. Patent 9,303,051 protects Morphic Form B of brincidofovir, also known as CMX001. Brincidofovir is a lipid-conjugated derivative of cidofovir designed to improve oral bioavailability. The claimed compound is:
The patent’s chemical name identifies the stereochemistry, nucleobase, hydroxymethyl substituent, phosphonic-acid monoester, and C16 hexadecyloxypropyl chain. A product that contains a different ester, stereoisomer, salt, or crystalline form may fall outside claim 1 unless it also satisfies the claim’s structural and XRPD limitations. What are the claims of U.S. Patent 9,303,051?Claim structure
Claims 2 through 6 are dependent claims and cannot be infringed independently of claim 1. They add analytical characteristics to the Morphic Form B limitation. What does claim 1 require?Claim 1 has two central elements:
The claim is not a broad claim to all brincidofovir. It is a polymorph claim. Amorphous brincidofovir, another polymorph, or a material lacking the required diffraction profile would present a non-infringement position if the accused product cannot be shown to contain Morphic Form B. The phrase “including peaks at about” gives the claim analytical tolerance. Courts would likely evaluate the meaning of “about,” the XRPD instrument, sample preparation, radiation source, peak resolution, and accepted crystallographic variation. Exact peak matching is not necessarily required, but a material with materially different diffraction behavior could fall outside the claim. How do claims 2 through 6 narrow the patent scope?Claims 2 through 4 add increasingly detailed peak requirements:
Claims 5 and 6 rely on substantial similarity to disclosed figures rather than a complete numerical list of peaks. Those claims may create interpretation issues because “substantially similar” is a functional comparison rather than a fully enumerated diffraction standard. The dependent claims provide fallback positions if a court narrows the scope of claim 1. They also create evidentiary disputes over:
What formulations are protected by U.S. Patent 9,303,051?Claim 7 protects a pharmaceutical composition containing Morphic Form B and a pharmaceutically acceptable carrier. The claim is broad as to the carrier. It does not require a particular tablet excipient, suspension vehicle, coating, dose, or manufacturing process. A composition containing the claimed Morphic Form B may fall within claim 7 even if its formulation differs from the commercial Tembexa formulation. The claim does not expressly require:
A formulation containing only another brincidofovir form would have a potential non-infringement position, but the analysis would depend on whether Morphic Form B is present as a component, contaminant, seed, intermediate, or transformation product. What method-of-use protection does the patent provide?Claim 8 covers administering Morphic Form B to treat a viral infection. Claim 9 lists a broad group of infections, including:
The method claims are not limited to smallpox. The virus list reaches multiple DNA and RNA virus indications, although enforceability would depend on written description, enablement, claim construction, and proof that the accused use practices every required limitation. For Tembexa, the commercially relevant FDA indication is treatment of human smallpox disease in adults and pediatric patients, including neonates. The FDA approved Tembexa under the Animal Rule because controlled human efficacy trials were not feasible for smallpox. FDA approval does not establish infringement of every listed method-of-use claim, but it confirms the commercial relevance of the orthopoxvirus portion of claim 9.[2] When does U.S. Patent 9,303,051 expire?The patent’s term is based on the applicable U.S. filing and priority history, not merely its 2016 issue date. Public patent records identify a term extending to approximately August 2030, before any adjustment or extension reflected in the controlling USPTO record.[1] The relevant exclusivity timeline is:
The patent is therefore expected to outlast FDA orphan exclusivity by roughly two years. A generic applicant could face a regulatory barrier from orphan exclusivity before the patent reaches its term, depending on the proposed indication and FDA regulatory pathway. Patent expiration should be confirmed against the current USPTO patent-term record and the FDA Orange Book listing before a launch or Paragraph IV filing. Patent-term adjustment, terminal disclaimers, patent-term extension, and Orange Book corrections can affect the operative date. What is the Orange Book status of Tembexa and U.S. Patent 9,303,051?Tembexa is an FDA-approved small-molecule product, not a biologic. Its generic competition would proceed through an ANDA, not a biosimilar application. The Orange Book is relevant because listed patents can trigger a 30-month stay if an ANDA applicant submits a Paragraph IV certification and the patent owner or NDA holder brings suit within the statutory period.[3] The patent’s commercial importance is strongest if it is listed against the approved Tembexa dosage forms and if the listed claims cover the drug product, its formulation, or an approved method of use. Claim 1 is a product-by-crystalline-form claim. Claim 7 is a composition claim. Claims 8 and 9 are method claims. A Paragraph IV applicant would likely evaluate:
Which companies are challenging Tembexa patent protection?Publicly established commercial competition for brincidofovir has been limited. The relevant competitive group includes:
No biosimilar pathway applies because brincidofovir is a chemically synthesized small molecule. A future generic applicant would need to address the listed patent estate through Paragraph IV, a Paragraph III certification, or another applicable ANDA certification. The absence of a publicly identified Paragraph IV dispute does not eliminate future challenge risk. A generic company can file an ANDA with a Paragraph IV certification before patent expiry, subject to the Hatch-Waxman framework and any applicable orphan-drug restrictions. What generic entry risks exist for Tembexa?Form B avoidanceThe most direct design-around strategy would be to manufacture a different brincidofovir polymorph, amorphous material, salt, solvate, or formulation that does not contain Morphic Form B. That strategy faces practical constraints. Polymorph conversion can occur during:
If Form B is thermodynamically favored or forms during processing, a nominally different starting material may still create infringement risk. Invalidity challengesPotential invalidity theories could include:
Polymorph patents often depend heavily on whether the claimed form was predictable, whether the prior art disclosed the same XRPD pattern, and whether the form had unexpected properties such as improved stability, solubility, manufacturability, or bioavailability. Formulation and process evidenceA generic applicant would need robust solid-state characterization. Relevant evidence would include:
The key question is not only what form is used at the beginning of manufacture. It is what form exists in the finished ANDA product and whether the product contains a detectable or legally significant amount of Form B. How strong is the patent estate for brincidofovir?U.S. Patent 9,303,051 is technically narrow but commercially meaningful. Strengths
Vulnerabilities
The estate is strongest against a generic product that uses the same crystallization process or deliberately reproduces Morphic Form B. It is weaker against a genuinely different solid form that remains stable through manufacture and administration. What patent litigation affects brincidofovir?No major publicly established U.S. Hatch-Waxman litigation campaign involving U.S. Patent 9,303,051 is identified in the cited FDA and patent materials. The absence of litigation is consistent with Tembexa’s limited commercial market, orphan-drug status, and government-stockpile orientation. A future ANDA challenge could generate litigation under 35 U.S.C. § 271(e)(2), followed by a potential 30-month stay under the Hatch-Waxman Act. The likely dispute would center on whether the proposed product contains Morphic Form B and whether the asserted claims are valid and properly listed. Are there licensing deals affecting brincidofovir?Brincidofovir was developed by Chimerix with U.S. government support and became Tembexa after FDA approval. The product’s principal commercial value has been linked to government preparedness and smallpox stockpiling rather than a broad retail antiviral market. The later ownership and commercialization history should be separated from patent ownership. A corporate acquisition or commercial supply agreement may transfer product rights without changing the original patent’s inventorship, priority, or expiration date. Patent assignments and the current NDA holder should be verified independently through USPTO assignment records and FDA product records.[1][2] How does U.S. Patent 9,303,051 compare with generic and biosimilar barriers?
Biosimilar risk is therefore not relevant to Tembexa. The commercial threat is generic substitution after the relevant regulatory and patent barriers expire or are successfully challenged. What revenue exposure does the patent create?The patent’s revenue exposure is concentrated rather than broad. Tembexa is an orphan smallpox product with demand driven primarily by government procurement, stockpile replenishment, and emergency preparedness. Key commercial variables are:
A successful generic launch could reduce product pricing in any commercial or government procurement channel that permits substitution. The financial impact would depend more on contract structure and stockpile procurement than on conventional chronic-use prescription volume. Key Takeaways
FAQs About U.S. Patent 9,303,051 and BrincidofovirDoes U.S. Patent 9,303,051 cover all forms of brincidofovir?No. The core claims are limited to Morphic Form B, identified by specified XRPD characteristics. Another polymorph or an amorphous form may fall outside the literal scope of the product claims. Can a generic company avoid the patent by using a different starting material?Not necessarily. Infringement depends on the form present in the accused product and the requirements of the asserted claims. A different starting material does not avoid infringement if manufacturing produces Morphic Form B in the finished dosage form. Is Tembexa protected by orphan-drug exclusivity?Yes. Tembexa received orphan-drug designation for smallpox. Orphan exclusivity is separate from patent protection and generally lasts seven years from approval for the protected indication. Could a generic launch before the patent expires?A generic applicant could file an ANDA with an appropriate patent certification before patent expiration. Commercial launch would depend on regulatory exclusivity, patent litigation, settlement terms, court outcomes, and any applicable stay. Does the patent cover treatment of COVID-19 or other unlisted infections?Claim 9 lists specific viral infections. It does not expressly list every possible viral disease. Infringement would depend on the exact accused use and whether that use falls within claim 8 or another asserted claim. References
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Drugs Protected by US Patent 9,303,051
| Applicant | Tradename | Generic Name | Dosage | NDA | Approval Date | TE | Type | RLD | RS | Patent No. | Patent Expiration | Product | Substance | Delist Req. | Patented / Exclusive Use | Submissiondate |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Emergent Biodefense | TEMBEXA | brincidofovir | SUSPENSION;ORAL | 214460-001 | Jun 4, 2021 | RX | Yes | Yes | ⤷ Start Trial | ⤷ Start Trial | Y | Y | METHOD OF TREATING HUMAN SMALLPOX DISEASE | ⤷ Start Trial | ||
| Emergent Biodefense | TEMBEXA | brincidofovir | TABLET;ORAL | 214461-001 | Jun 4, 2021 | RX | Yes | Yes | ⤷ Start Trial | ⤷ Start Trial | Y | Y | METHOD OF TREATING HUMAN SMALLPOX DISEASE | ⤷ Start Trial | ||
| >Applicant | >Tradename | >Generic Name | >Dosage | >NDA | >Approval Date | >TE | >Type | >RLD | >RS | >Patent No. | >Patent Expiration | >Product | >Substance | >Delist Req. | >Patented / Exclusive Use | >Submissiondate |
International Family Members for US Patent 9,303,051
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| Australia | 2011295937 | ⤷ Start Trial | |||
| Brazil | 112013004925 | ⤷ Start Trial | |||
| Canada | 2809679 | ⤷ Start Trial | |||
| China | 103209985 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
