Details for Patent: 5,686,570
Summary for Patent: 5,686,570
| Title: | Platelet aggregation inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | An assay for screening snake venom for the presence or absence of platelet aggregation inhibitors (PAIs) based on specific receptor binding is described. Using this assay, the identification and characterization of PAIs in a wide range of snake venom samples was accomplished. The isolated and purified PAI from several of these active snake venoms is described and characterized. In addition, PAIs lacking the Arg-Gly-Asp (RGD) adhesion sequence but containing K*-(G/Sar)-D wherein K* is a modified lysyl residue of the formula wherein each R1 is independently H, alkyl(1-6C) or at most one R1 is R2 --C═NR3 wherein R2 is H, alkyl(1-6C), phenyl or benzyl, or is NR4 2 in which each R4 is independently H or alkyl(1-6C) and R3 is H, alkyl(1-6C), phenyl or benzyl, or R2 --C═NR3 is a radical selected from the group consisting of: ##STR1## where m is an integer of 2-3, and each R5 is independently H or alkyl(1-6C);and wherein one or two (CH2) may be replaced by O or S provided said O or S is not adjacent to another heteroatomare prepared and shown to specifically inhibit the binding of fibrinogen or von Willebrand Factor to GP IIb-IIIa. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Robert M. Scarborough, David Lawrence Wolf, Israel F. Charo | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | COR Therapeutics Inc , Millennium Pharmaceuticals Inc | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US08/463,765 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Patent Claim Types: see list of patent claims | Composition; Compound; | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | US Patent 5,686,570: Eptifibatide Claims, Patent Scope, Expiration, and Generic RiskUS Patent No. 5,686,570 covers the cyclic platelet aggregation inhibitor eptifibatide, marketed as Integrilin. Its core claims protect the eptifibatide molecule, physiologically acceptable salts, pharmaceutical compositions, and a structure-defined platelet aggregation inhibitor with preferential activity against platelet glycoprotein IIb/IIIa over vitronectin and fibronectin receptors. The patent was assigned to COR Therapeutics, Inc. and issued on Nov. 11, 1997. Its 20-year US patent term expired in 2014. The patent therefore does not currently block generic eptifibatide development or marketing. What drug does US Patent 5,686,570 protect?The claims identify eptifibatide, a cyclic peptide glycoprotein IIb/IIIa antagonist. The structural elements recited in the claims are:
The claimed molecule corresponds to eptifibatide, whose pharmacological target is the platelet glycoprotein IIb/IIIa receptor. Blocking this receptor prevents fibrinogen and von Willebrand factor from cross-linking activated platelets. FDA approved Integrilin injection in 1998 for use in acute coronary syndromes and during percutaneous coronary intervention. The approved product contains eptifibatide as a sterile injectable solution. [2] What are the independent claims in US Patent 5,686,570?The patent has three principal claim categories. Claim 1: Compound claimClaim 1 covers the specified cyclic peptide structure and its physiologically acceptable salts. The claim is not a broad genus covering all IIb/IIIa antagonists. It fixes the main structural variables:
Because the listed alternatives are narrowed to specific residues, claim 1 operates primarily as a product claim directed to eptifibatide and its salts. Claim 4: Platelet aggregation inhibitor claimClaim 4 repeats substantially the same molecular definition but characterizes the compound as a platelet aggregation inhibitor. This functional language does not materially expand the chemical scope. A compound still must satisfy the structural limitations. A competing product with a different peptide sequence would not fall within claim 4 merely because it also inhibited platelet aggregation. Claim 7: Selective receptor-binding claimClaim 7 covers the same structure where the inhibitor has greater inhibition of:
than of:
This claim adds a pharmacological selectivity limitation. It is narrower than a claim covering any platelet aggregation inhibitor because the product must meet the specified comparative receptor-binding property. How do claims 2, 3, 5, 6, 8, and 9 narrow the patent?Claims 2, 5, and 8 are dependent claims that identify the specific structural formula shown in the patent figures. They remove ambiguity from the generalized formula in claims 1, 4, and 7. Claims 3, 6, and 9 cover acid addition salts of the specifically identified compound. The dependent claims have limited practical breadth because they remain tied to the same active peptide. Their principal legal purpose is to provide fallback positions if a broader parent claim is challenged.
What pharmaceutical compositions are protected by claims 10 and 11?Claim 10 covers a pharmaceutical composition containing a compound of claims 1 through 9 mixed with a pharmaceutically acceptable excipient. Claim 11 requires the compound to be present in an amount effective to inhibit platelet aggregation. These claims are composition claims, not detailed formulation claims. They do not expressly require:
The claims could cover an injectable composition containing eptifibatide and conventional excipients. Their scope does not appear to depend on the exact formulation used in the commercial Integrilin product, provided the composition contains the claimed compound and the excipient combination satisfies ordinary pharmaceutical-composition requirements. What formulations are protected by US Patent 5,686,570?The patent protects the active ingredient in admixture with a pharmaceutically acceptable excipient, but it does not create a comprehensive formulation monopoly. A generic eptifibatide injection could avoid infringement of claim 10 if it did not contain the claimed active compound. In practice, however, a generic eptifibatide product necessarily contains eptifibatide, so the principal historical risk came from the expired compound claims rather than from a separate formulation-specific patent. The patent does not appear to claim:
Does the patent contain method-of-use claims?No conventional method-of-treatment claim appears in the supplied claims. The patent claims compounds and compositions. Claims 4 and 7 describe pharmacological activity, but they do not recite administering eptifibatide to a patient to treat acute coronary syndrome, myocardial infarction, or another disease. Claim 11 requires an effective amount in the composition, but it is still drafted as a composition claim. It is not a conventional method claim of the form “administering to a patient.” This distinction matters for Orange Book analysis. A patent directed only to a compound or composition is generally listed differently from a patent claiming a specific approved use. The supplied claims do not establish a separate method-of-use patent covering a particular clinical indication. When did US Patent 5,686,570 expire?The patent’s nominal US patent term ended in 2014, approximately 20 years after the relevant nonprovisional filing date. The patent issued on Nov. 11, 1997, as US 5,686,570. Public patent records identify the expiration period as May 2014. [1]
Patent term extension under 35 U.S.C. § 156 can extend certain pharmaceutical patents after regulatory review. The available patent and product records do not establish a current enforceable extension for US 5,686,570. The patent is therefore not a current US exclusivity barrier. What is the Orange Book status of eptifibatide?Integrilin was approved under NDA 20-718. The Orange Book historically listed US 5,686,570 in connection with the product. Any listing associated with that patent no longer creates an active patent barrier because the patent term has expired. [3] The relevant regulatory distinction is:
Eptifibatide is a chemically defined peptide drug, not a biologic licensed under section 351 of the Public Health Service Act. A follow-on product would generally use the generic-drug framework rather than the biosimilar pathway. Which companies challenged or could challenge the patent?The principal commercial opportunity arose after expiration, when generic manufacturers could file ANDAs without facing an unexpired patent claim. A Paragraph IV certification would have been relevant before the 2014 expiration date if an ANDA applicant asserted that the patent was invalid, unenforceable, or not infringed. After expiration, a Paragraph IV challenge to this patent would no longer provide the same commercial value because the patent could not block launch. The available record does not establish a material current Paragraph IV litigation proceeding involving US 5,686,570. The commercial issue is therefore generic entry after expiration, not ongoing patent litigation. Potential generic applicants include manufacturers of sterile injectable peptide products. The main competitive barriers are technical and regulatory:
These are manufacturing and approval risks, not surviving patent barriers. What patent litigation affects eptifibatide?US 5,686,570 was the principal patent associated with the core eptifibatide molecule. Its expiration removes the strongest historical litigation basis against a generic that uses the same active ingredient. The supplied claims do not show a separate surviving patent covering:
A complete current freedom-to-operate conclusion would require a live search of later continuations, divisionals, formulation filings, process patents, and third-party rights. The patent itself, however, no longer provides enforceable exclusivity. What licensing deals affected eptifibatide commercialization?COR Therapeutics developed eptifibatide and commercialized it through a strategic relationship with Schering-Plough. Schering-Plough marketed Integrilin in the United States and other markets. Merck later acquired Schering-Plough in 2009. The commercial relationship was important because patent ownership and product commercialization were separate business functions:
The license or commercialization arrangement did not extend the statutory life of US 5,686,570. How strong was the patent estate for eptifibatide?The core compound patent was commercially strong during its term because it covered the active molecule itself. A generic using the same eptifibatide molecule would have had difficulty avoiding claims 1, 2, 4, 5, 7, or 8 while the patent remained enforceable. Its strength was based on claim type:
The patent estate is now weak from an exclusivity standpoint because the principal patent has expired. Patent strength after expiration is effectively zero for blocking generic entry, although the patent remains relevant as prior art and as a historical record of the product’s claimed structure. What generic launch risks exist for eptifibatide?A generic eptifibatide launch is primarily exposed to regulatory and manufacturing risk. Regulatory riskThe applicant must demonstrate pharmaceutical equivalence and bioequivalence or otherwise satisfy FDA requirements for the injectable product. For a parenteral product, FDA may evaluate whether the formulation and route of administration permit reliance on applicable waivers or alternative equivalence standards. [4] Manufacturing riskEptifibatide contains a disulfide-linked cyclic peptide. Manufacturing controls must address:
Commercial riskEptifibatide competes with other antiplatelet agents used in acute coronary intervention, including intravenous cangrelor and other historical GP IIb/IIIa inhibitors such as abciximab and tirofiban. Product demand depends on hospital protocols, cardiology practice, formulary placement, and the continuing use of intravenous GP IIb/IIIa therapy. How does eptifibatide compare with tirofiban and abciximab?
Eptifibatide’s distinctive technical feature is its cyclic peptide structure with a disulfide bond and homoarginine-containing binding motif. Its development and manufacturing profile therefore differ from those of small-molecule tirofiban and antibody-based abciximab. What is the current commercial exposure from US Patent 5,686,570?The patent creates no current direct revenue protection for Integrilin. All historical branded revenue associated with the patent depended on exclusivity before its 2014 expiration. Current commercial exposure is determined by:
The patent does not support a current royalty claim against a generic eptifibatide product based solely on use of the claimed molecule. Key Takeaways
FAQsIs US Patent 5,686,570 still enforceable?No. The patent’s US term expired in 2014, eliminating its ability to block current generic eptifibatide marketing. Does the patent cover Integrilin specifically?Yes. The claimed cyclic peptide structure corresponds to eptifibatide, the active ingredient in Integrilin. Does the patent cover eptifibatide hydrochloride or other salts?The claims cover physiologically acceptable acid or basic addition salts, including the salt forms falling within the claim language. Is a generic eptifibatide product a biosimilar?No. Eptifibatide is a chemically defined peptide drug. A generic applicant would generally pursue an ANDA rather than a biosimilar application under section 351(k). Are eptifibatide manufacturing processes still patent protected?US 5,686,570 does not contain the supplied manufacturing-process claims. Separate later patents would need to be reviewed independently, but this patent itself does not create current process exclusivity. References
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Drugs Protected by US Patent 5,686,570
| Applicant | Tradename | Generic Name | Dosage | NDA | Approval Date | TE | Type | RLD | RS | Patent No. | Patent Expiration | Product | Substance | Delist Req. | Patented / Exclusive Use | Submissiondate |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| >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 5,686,570
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| European Patent Office | 0477295 | ⤷ Start Trial | SPC/GB99/046 | United Kingdom | ⤷ Start Trial |
| European Patent Office | 0477295 | ⤷ Start Trial | C990043 | Netherlands | ⤷ Start Trial |
| European Patent Office | 0477295 | ⤷ Start Trial | 51/1999 | Austria | ⤷ Start Trial |
| Austria | 146969 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
