Details for Patent: 7,297,761

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Summary for Patent: 7,297,761

Title:	Pharmaceutical compositions containing exendins
Abstract:	Methods for treating conditions or disorders which can be alleviated by reducing food intake are disclosed which comprise administration of an effective amount of an exendin or an exendin agonist, alone or in conjunction with other compounds or compositions that affect satiety. The methods are useful for treating conditions or disorders, including obesity, Type II diabetes, eating disorders, and insulin-resistance syndrome. The methods are also useful for lowering the plasma glucose level, lowering the plasma lipid level, reducing the cardiac risk, reducing the appetite, and reducing the weight of subjects. Pharmaceutical compositions for use in the methods of the invention are also disclosed.
Inventor(s):	Nigel Robert Arnold Beeley, Kathryn S. Prickett, Sunil Bhavsar, Andrew Young, Bronislava Gedulin
Assignee:	Amylin Pharmaceuticals LLC
Application Number:	US10/894,999
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,297,761
Patent Claim Types: see list of patent claims	Composition; Compound;

US Patent 7,297,761: Exendin Pharmaceutical Compositions, Claim Scope and Patent Landscape

US Patent 7,297,761 protects pharmaceutical compositions containing exendin-3 or exendin-4 in an acidic buffered formulation, with the broadest independent claims focused on acetate-buffered or otherwise buffered compositions at approximately pH 3.5 to 5. The principal commercial relevance was Byetta, the exenatide injection marketed by Amylin Pharmaceuticals and later AstraZeneca. The patent’s statutory term ended in December 2022, so it no longer creates a current U.S. patent barrier to generic exenatide development.

The patent remains important as a historical formulation patent because it illustrates the technical and claim strategies used to protect exendin products after the active peptide itself had been disclosed in earlier patent families.

What does US Patent 7,297,761 cover?

The patent covers liquid pharmaceutical compositions containing an exendin peptide and a buffer. Its claims extend to:

• Exendin-4 and exendin-3;
• Acetate buffers and, under the broader claims, other buffers;
• Formulations with pH from approximately 3.5 to 5;
• Mannitol and other isotonicity agents;
• Pharmaceutical excipients;
• Specified dosing ranges;
• Combination formulations containing appetite- or weight-reducing agents;
• Multiple administration routes;
• Certain exendin-4 analogs and truncated or amidated variants.

The patent does not claim exendin-4 as a molecule in the abstract. It claims compositions in which the peptide is combined with specified formulation components or formulation characteristics.

The independent claims are claims 1, 18 and 22.

Independent claim	Core required elements	Relative breadth
Claim 1	Exendin-4 plus an acetate buffer	Broad for acetate-buffered exendin-4 compositions; no express pH limitation
Claim 18	Exendin-4, mannitol and acetate buffer, with pH about 3.5 to 5.0	Narrower, compositionally specific
Claim 22	Exendin-3 or exendin-4, a buffer and pH about 3.5 to 5	Broadest species coverage, but pH-limited

The use of “comprising” makes the claims open-ended. A formulation can contain additional ingredients and still fall within the claim if all required elements are present.

How are the independent claims different?

Claim 1: acetate-buffered exendin-4

Claim 1 requires only two core components:

1. Exendin-4; and
2. An acetate buffer.

The claim does not expressly require mannitol, a particular pH, a particular dose or a particular route of administration. Dependent claims add those limitations.

A formulation containing exendin-4, sodium acetate or another acetate buffering system, and additional excipients could fall within claim 1 even if it does not contain mannitol or an isotonicity agent.

The main claim-construction issue is whether the accused product contains an “acetate buffer.” A formulation using acetic acid and sodium acetate would present a straightforward case. A formulation using acetate only as an incidental counterion or residual process impurity would raise a more difficult issue.

Claim 18: exendin-4, mannitol and acetate at acidic pH

Claim 18 is narrower because it requires all of the following:

• Exendin-4;
• Mannitol;
• An acetate buffer; and
• A pH from approximately 3.5 to 5.0.

This claim most closely targets a conventional stabilized injectable formulation containing exenatide, acetate and mannitol.

A product could avoid literal infringement of claim 18 by omitting mannitol, using a different buffer, or operating outside the claimed pH range. Those design choices would not necessarily avoid claim 1 or claim 22.

Claim 22: buffered exendin-3 or exendin-4 at pH 3.5 to 5

Claim 22 is the broadest independent claim in terms of buffer identity and exendin species. It requires:

• A buffer;
• Exendin-3 or exendin-4; and
• A pH from approximately 3.5 to 5.

Unlike claim 1, claim 22 is not limited to acetate. Unlike claim 18, it does not require mannitol.

A buffered exendin-4 composition using phosphate, citrate or another pharmaceutically acceptable buffer could potentially satisfy claim 22 if its pH is within the claimed range.

The principal limitation is the pH range. A product at pH 5.5 would not literally satisfy claim 22, although an equivalence analysis could become relevant in litigation depending on the formulation’s technical characteristics and prosecution history.

What dependent-claim limitations are commercially significant?

pH limitations

Claims 2, 3 and 22 limit the composition to an acidic pH range.

• Claims 2 and 22: approximately pH 3.5 to 5;
• Claim 3: approximately pH 4.5;
• Claim 18: approximately pH 3.5 to 5.0.

The “about” language creates a potential boundary dispute. Courts generally interpret “about” in light of the specification, analytical precision, manufacturing tolerances and the relevant technical field. A formulation at pH 5.05 would not automatically infringe or avoid infringement without considering the patent’s intrinsic evidence.

Mannitol and isotonicity agents

Claim 18 specifically requires mannitol. Claim 4 and claim 24 cover isotonicity agents, including:

• Sodium chloride;
• Dextrose;
• Boric acid;
• Sodium tartrate;
• Propylene glycol;
• Polyols; and
• Combinations of those agents.

Mannitol is a polyol and is expressly recited in claim 18. The list is not necessarily exhaustive for infringement of claim 1 or claim 22, because those claims do not require an isotonicity agent. It becomes limiting only in claims that depend on the isotonicity-agent limitation or expressly require mannitol.

Excipients

Claims 6 and 26 identify a broad list of pharmaceutically acceptable carriers and excipients, including:

• Calcium carbonate;
• Calcium phosphate;
• Lactose;
• Glucose;
• Sucrose;
• Starch;
• Cellulose derivatives;
• Gelatin;
• Oils; and
• Polyethylene glycol.

These claims do not independently protect the use of those excipients with exendin. They narrow the claims from which they depend. A formulation lacking the listed excipients may still infringe the relevant independent claim.

Weight-management combination products

Claims 7 through 9 and 21, 27 through 29 cover combinations of exendin with a second substance that reduces food intake, appetite, body weight or obesity.

The listed substances include:

• Amylin;
• Amylin agonists;
• Leptin;
• Cholecystokinin;
• CCK-8;
• Calcitonin; and
• Human amylin.

These claims are relevant to combination-product development but do not cover exendin monotherapy unless the additional substance is present.

Dose limitations

Claims 10 through 16 and 19, 20 and 30 through 34 specify dose ranges. The ranges include:

• Approximately 0.1 to 100 micrograms per kilogram per day;
• Approximately 0.1 to 10 micrograms per kilogram per day;
• Approximately 0.1 to 1 microgram per kilogram per day;
• Approximately 0.01 to 5 milligrams per day;
• Approximately 0.01 to 2 milligrams per day;
• Approximately 0.01 to 1 milligram per day; and
• Approximately 0.01 to 0.5 milligram per day.

The dose claims are dependent composition claims. They require the claimed composition to be formulated to provide the stated dose, but they do not convert the patent into a general method-of-treatment patent.

The supplied claim text contains a duplication: claims 33 and 34 both recite a daily dose of approximately 0.01 to 0.5 mg. That duplication does not expand the scope beyond the shared limitation.

Administration routes

Claim 17 and claim 35 cover formulations for:

• Intravenous;
• Intraperitoneal;
• Subcutaneous;
• Intramuscular;
• Oral;
• Topical;
• Transmucosal; and
• Pulmonary administration.

The route limitation applies only to those dependent claims. Claim 1 and claim 22 are not limited to subcutaneous injection or any other route.

What exendin molecules are covered?

Claim 22 covers exendin-3 and exendin-4. Claim 36 narrows the scope to particular exendin-4 forms, including:

• Exendin-4 (1-30);
• Exendin-4 (1-30) amide;
• Exendin-4 (1-28) amide;
• 14Leu, 25Phe exendin-4 amide;
• 14Leu, 25Phe exendin-4 (1-28) amide; and
• 14Leu, 22Ala, 25Phe exendin-4 (1-28) amide.

Claim 37 narrows the composition to exendin-4.

The claim set therefore reaches beyond commercially marketed native exenatide if a listed analog is formulated within the required buffer and pH parameters. It does not automatically cover every GLP-1 receptor agonist. Liraglutide, dulaglutide, semaglutide and lixisenatide are chemically distinct molecules and would not satisfy the exendin limitation.

When did US Patent 7,297,761 lose exclusivity?

US Patent 7,297,761 was granted on November 20, 2007. Its priority and filing history place the ordinary U.S. patent term in December 2022. The patent therefore no longer provides an enforceable U.S. patent exclusion for the claimed formulations.

Event	Date or period
Earliest priority period	December 2000
U.S. filing period	December 2001
U.S. patent grant	November 20, 2007
Statutory patent-term endpoint	December 2022
Current status	Expired by term

Patent expiration does not invalidate the historical relevance of the patent. It removes the right to exclude others after the term ends. It also means that a current generic applicant would not need to file a Paragraph IV certification against this patent solely because the patent once covered the reference product.

What was the FDA and Orange Book relevance?

Byetta, the principal U.S. exenatide product associated with this formulation technology, was approved by FDA in 2005. Exenatide is a synthetic peptide drug rather than a monoclonal antibody or other biologic. A follow-on exenatide product may therefore proceed through an abbreviated new drug application if it satisfies the applicable requirements for pharmaceutical equivalence, bioequivalence, quality and labeling.

The patent’s relevance to the Orange Book was formulation-based. It did not provide a basic compound patent on all exenatide. An Orange Book listing would have affected the timing and litigation posture of an ANDA applicant while the patent remained unexpired.

After expiration, the patent no longer supports a current Paragraph IV barrier. A generic applicant could still need to address other unexpired patents, regulatory exclusivities, device-related rights, manufacturing patents or non-patent product requirements associated with the reference product.

There is no biosimilar pathway issue for exenatide in the same sense as for insulin analogs, monoclonal antibodies or other licensed biologics. The principal competitive route is a generic or follow-on peptide drug pathway, not a traditional biosimilar challenge.

What Paragraph IV challenges and litigation risks did the patent create?

While unexpired, the patent could be challenged through an ANDA Paragraph IV certification. A generic applicant could assert that:

• The patent claims were invalid;
• The claims were unenforceable; or
• The proposed product would not infringe.

The strongest non-infringement strategies would have focused on formulation design:

Design-around approach	Likely claim target avoided
Use citrate, phosphate or another non-acetate buffer	Claim 1 and acetate-dependent claims
Use pH outside approximately 3.5 to 5	Claims 2, 3, 18 and 22
Omit mannitol	Claim 18
Use a non-exendin GLP-1 agonist	All claims
Use a different active peptide not covered by claim 22	Claims 22 and its dependents
Avoid listed combination agents	Claims 7-9, 21 and 27-29

Those strategies would require confirmation that the alternative formulation remains stable, manufacturable and bioequivalent. Avoiding one claim does not necessarily avoid all claims. For example, replacing acetate with citrate could avoid claim 1 but still leave potential exposure under claim 22 if the product remains an exendin-4 formulation at pH 3.5 to 5.

The patent’s expired status eliminates current infringement exposure under this patent. Any historical Paragraph IV litigation or settlement terms would need to be analyzed separately from current enforceability.

How strong was the patent estate?

The patent was moderately strong as a formulation patent but narrow relative to a composition-of-matter patent.

Strengths

• Claim 1 captured acetate-buffered exendin-4 formulations without requiring mannitol or a stated pH.
• Claim 22 covered buffered exendin-3 and exendin-4 across multiple buffer systems.
• The pH range corresponded to a commercially plausible acidic injectable formulation.
• Claim 18 targeted a defined exendin-4, mannitol and acetate combination.
• The open-ended “comprising” language made it difficult to avoid infringement merely by adding excipients.

Weaknesses

• The claims did not cover exendin-4 as a molecule.
• The pH and buffer limitations created practical design-around options.
• The composition claims could face validity challenges based on earlier exendin disclosures, known peptide formulation practice and obviousness arguments.
• Dose and route limitations were dependent and did not materially expand the independent claims.
• The patent expired in 2022.

The estate’s commercial value depended on whether the reference product used the claimed formulation and whether competing products needed the same acidic acetate-buffered system. A product using a different buffer or pH could reduce exposure substantially.

How does this patent compare with competing GLP-1 formulation patents?

US 7,297,761 is materially narrower than a compound patent and technically different from later formulation patents covering long-acting delivery systems.

Patent category	Typical protected subject matter	Relevance to exenatide competition
Compound patent	Exendin-4 structure or analog	Broadest molecule-level exclusion
Use patent	Treatment of diabetes, obesity or appetite disorders	Can affect labeled-use strategies
Formulation patent	Buffer, pH, excipient and stability profile	Targets the finished dosage form
Depot or microsphere patent	Extended-release delivery system	Relevant to products such as long-acting exenatide
Device patent	Pen injector, cartridge or delivery mechanism	Can affect product presentation
Manufacturing patent	Peptide synthesis, purification or formulation process	May create process-specific barriers

US 7,297,761 is a conventional formulation patent. It does not, based on the supplied claims, cover the extended-release microsphere technology used for once-weekly exenatide products. It also does not cover liraglutide, semaglutide, dulaglutide or other non-exendin GLP-1 agonists.

What generic entry risks exist for exenatide products?

The patent-specific risk from US 7,297,761 is now zero after expiration. Before expiration, risk depended on the formulation:

1. An acetate-buffered exenatide-4 product had the clearest exposure under claim 1.
2. A product at pH 3.5 to 5 using any buffer had potential exposure under claim 22.
3. A product containing exenatide-4, mannitol and acetate at the claimed pH had the most concentrated exposure under claim 18.
4. A product with a different buffer and pH outside the claimed range had the strongest design-around position.
5. A product using a different GLP-1 active ingredient was outside the literal exendin scope.

Current market-entry analysis must focus on the remaining patent and regulatory landscape, including:

• Other exenatide compound or use patents;
• Long-acting delivery patents;
• Injection-device patents;
• Manufacturing and purification patents;
• FDA exclusivity records;
• Reference-product labeling;
• Product-specific bioequivalence requirements; and
• Any later patent families owned by Amylin, AstraZeneca, Eli Lilly, Teva, Amneal, Sandoz or other developers.

What are the key takeaways from US Patent 7,297,761?

• Claim 1 is the principal acetate-buffered exendin-4 claim.
• Claim 22 is broader in buffer identity but requires pH of approximately 3.5 to 5.
• Claim 18 is narrower and requires mannitol, acetate and the claimed acidic pH.
• The patent covers formulations, not exendin-4 as a molecule.
• Dose, excipient, isotonicity, combination-agent and administration-route claims are dependent limitations.
• The patent does not cover non-exendin GLP-1 agonists.
• The patent does not cover extended-release exenatide delivery systems merely because they contain exenatide.
• The U.S. patent term ended in December 2022.
• The patent is no longer a current Paragraph IV barrier or enforceable generic-entry restriction.

FAQs about US Patent 7,297,761 and exendin formulations

Does US 7,297,761 cover Byetta?

Historically, the claims were relevant to Byetta-type exenatide formulations, particularly formulations containing exenatide-4, acetate buffer and an acidic pH. The patent expired in December 2022.

Does the patent cover Bydureon?

The supplied claims do not specifically claim extended-release microspheres, poly-lactide-co-glycolide systems or other depot technologies. Bydureon-related exposure would depend on other patents and the actual formulation.

Can a generic exenatide product use acetate buffer today?

Yes, expiration of US 7,297,761 removes this patent as a current exclusionary barrier. The generic applicant must still satisfy FDA quality, bioequivalence, labeling and manufacturing requirements and address any other unexpired rights.

Is exendin-4 the same as semaglutide?

No. Exendin-4 is the active peptide in exenatide. Semaglutide is a chemically modified GLP-1 analog with a different molecular structure and is outside the exendin limitations in US 7,297,761.

Does claim 22 cover any peptide at pH 4?

No. Claim 22 requires a buffer, exendin-3 or exendin-4, and a pH of approximately 3.5 to 5. A non-exendin peptide does not satisfy the claimed active-ingredient limitation.

References

1. United States Patent and Trademark Office. (2007). U.S. Patent No. 7,297,761, Exendin pharmaceutical compositions.
2. U.S. Food and Drug Administration. (2005). FDA approves Byetta for the treatment of type 2 diabetes.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
4. U.S. Food and Drug Administration. (2024). Approved drug products and patent and exclusivity information.
5. United States Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation provisions.

Drugs Protected by US Patent 7,297,761

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 7,297,761

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0996459		CA 2007 00034	Denmark
European Patent Office	0996459		91342	Luxembourg
European Patent Office	0996459		C00996459/01	Switzerland
European Patent Office	0996459		0790031-9	Sweden
European Patent Office	0996459		464	Finland
European Patent Office	0996459		SZ 31/2007	Austria
Austria	304864