United States Patent 8,299,209: Pasireotide Liquid Formulation Claims, Patent Scope and Generic Entry Risk

U.S. Patent No. 8,299,209 protects parenteral liquid formulations containing tartaric acid and a defined somatostatin analogue, with narrower claims directed to pasireotide and its di-aspartate salt. The commercially relevant embodiment is pasireotide diaspartate, the active pharmaceutical ingredient in Novartis' Signifor injection. The patent does not broadly cover every pasireotide product. A potentially infringing product must practice the formulation limitations, including liquid parenteral delivery and tartaric acid, either literally or under the doctrine of equivalents.

The patent's primary commercial value is formulation protection. It does not appear to be a basic composition-of-matter patent for pasireotide. The nominal patent term is tied to the earliest effective nonprovisional or PCT filing date and should be confirmed against USPTO term-adjustment records. Based on the public priority record, the expected ordinary expiration is in 2026, subject to patent-term adjustment, terminal disclaimers, or other statutory changes.[1]

What does U.S. Patent 8,299,209 protect?

The patent protects a liquid formulation for parenteral administration comprising two required technical elements:

Tartaric acid.
A somatostatin analogue falling within the claimed formula II genus.

Claim 1 is the independent formulation claim. Claims 2 through 5 narrow the scope by specifying salt form, pH, and the particular somatostatin analogue pasireotide.

Claim	Principal limitation	Commercial significance
1	Liquid parenteral formulation containing tartaric acid and a formula II somatostatin analogue	Broadest formulation claim
2	Claim 1, with the somatostatin analogue in aspartate di-salt form	Covers pasireotide diaspartate-type formulation
3	Claim 1, with pH of about 4 to about 4.5	Narrows the formulation by acidity
4	Claim 1, where the analogue is the specified cyclic peptide	Directly targets pasireotide or its defined pharmaceutical salts
5	Claim 2, where the analogue is the specified cyclic peptide	Narrowest express claim to pasireotide in aspartate di-salt form

Claim 5 is the most commercially specific claim. It combines the formulation vehicle, tartaric acid, the pasireotide peptide, and the aspartate di-salt form.

What compound is covered by claims 4 and 5?

The compound in claims 4 and 5 is pasireotide, also known as SOM230. The claimed cyclic peptide is:

cyclo[{4-(NH2-C2H4-NH-CO-O)Pro}-Phg-DTrp-Lys-Tyr(4-Bzl)-Phe]

Pasireotide is a cyclohexapeptide somatostatin receptor ligand. It is marketed by Novartis as pasireotide diaspartate under the Signifor brand. Signifor injection is supplied for subcutaneous administration, while Signifor LAR is a separate long-acting intramuscular depot product and should not be assumed to fall within these liquid formulation claims.[2]

The claim language uses "the somatostatin" broadly in claims 1 through 3, but claim 4 expressly identifies pasireotide. Claim 5 adds the aspartate di-salt limitation.

How broad is independent claim 1?

Claim 1 is materially broader than the pasireotide-specific claims. It does not require:

Pasireotide specifically;
An aspartate salt;
A pH between 4 and 4.5;
A particular concentration;
A particular injection device;
A particular preservative;
A particular container;
A particular dosing schedule.

The claim instead relies on a Markush definition of the somatostatin analogue. The formula requires the claimed peptide scaffold and permits variation at the specified substituent. The R group may contain an amino-containing or guanidine-containing C2-C6 alkylene chain, with the relevant nitrogen substituents being hydrogen or C1-C4 alkyl.

A formulation can therefore fall within claim 1 even if it does not contain pasireotide, provided that:

It is liquid;
It is suitable for parenteral administration;
It contains tartaric acid; and
It contains a somatostatin analogue within the formula II definition.

The phrase "in free form, salt form, or protected form" expands the chemical-form coverage. A product cannot necessarily avoid claim 1 merely by changing the counterion, using a protected intermediate, or presenting the peptide in a different salt form.

What does claim 3 add through the pH limitation?

Claim 3 requires a formulation pH of about 4 to about 4.5. The word "about" creates a claim-construction issue. Courts generally interpret "about" in view of the specification, examples, measurement precision, and technical context. A formulation at pH 4.1 or 4.4 would present a strong literal-infringement risk. A formulation at pH 3.8 or 4.7 would require a more fact-specific analysis.

The pH limitation may be important because tartaric acid performs more than a nominal excipient function. The combination can affect:

Peptide solubility;
Chemical stability;
Aggregation;
Injection-site tolerability;
Shelf life;
Compatibility with the intended container and closure system.

A generic manufacturer that uses citrate, acetate, phosphate, or another acidulant instead of tartaric acid may reduce literal infringement risk. That design-around would not eliminate risk if the patent's specification and prosecution history support an equivalents theory, but excipient substitution is a more credible strategy than merely changing the tartaric acid concentration.

What formulations are protected by U.S. Patent 8,299,209?

The principal protected formulation is an acidic, liquid, parenteral pasireotide formulation containing tartaric acid. Claim 5 is the closest claim to the commercial pasireotide diaspartate embodiment.

Potentially covered products include:

A ready-to-use pasireotide diaspartate injection containing tartaric acid;
A liquid pasireotide formulation adjusted to approximately pH 4 to 4.5;
A pharmaceutical salt of pasireotide in a tartaric-acid-containing injectable solution;
A formulation using pasireotide in a different salt form, where the product satisfies claim 1 or claim 4.

A formulation may avoid claim 5 but still implicate claim 1 or claim 4. For example, a pasireotide formulation that uses a non-aspartate salt would not meet claim 5's aspartate di-salt limitation, but it could remain within claim 4 because claim 4 covers pasireotide "or a pharmaceutically acceptable salt thereof."

The claims do not expressly require that tartaric acid be the sole buffer or acidulant. A product containing tartaric acid together with another buffer could still satisfy the claims.

Does the patent cover Signifor and Signifor LAR?

Signifor injection

Signifor injection contains pasireotide diaspartate and is administered subcutaneously. A product with tartaric acid and the claimed pasireotide salt would align closely with claim 5. The formulation claim is therefore commercially relevant to the immediate-release injectable product.[2]

Signifor LAR

Signifor LAR is a long-acting intramuscular formulation using a depot delivery system. Its dosage form, administration route, and manufacturing process differ from a simple liquid formulation for parenteral administration. The existence of this patent does not establish infringement by Signifor LAR.

A depot product could raise separate issues under other patents covering:

Microsphere or depot technology;
Reconstitution before injection;
Long-acting release profiles;
Manufacturing processes;
Particle-size control;
Peptide stabilization.

Those issues are distinct from the five claims provided for U.S. Patent 8,299,209.

What is the patent's likely expiration date?

The ordinary U.S. patent term is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment and other statutory rules.[3] The patent's public priority record indicates an effective priority date in 2005. On that basis, the ordinary term would end in approximately 2026.

Item	Assessment
U.S. patent	8,299,209
Patent type	Utility patent
Patent subject	Liquid somatostatin analogue formulations
Commercial analogue	Pasireotide
Key assignee	Novartis AG
Earliest public priority period	2005
Nominal ordinary term	Approximately 20 years from the effective nonprovisional/PCT filing date
Expected ordinary expiration	Approximately 2026
Patent-term adjustment	Must be checked in USPTO Patent Center
FDA product relevance	Signifor pasireotide injection

The priority date alone does not establish the final enforceable expiration date. USPTO patent-term adjustment, terminal disclaimer information, and any patent-term extension record control the final date. A regulatory extension for a formulation patent would also require confirmation in the USPTO and FDA records. The Hatch-Waxman regulatory exclusivity period for pasireotide is separate from the patent term.[3][4]

What is the FDA and Orange Book status of pasireotide?

The FDA approved Signifor injection in December 2012 for Cushing's disease and later approved pasireotide products for additional indications, including acromegaly.[2] Pasireotide is a small-molecule peptide drug, not a biologic approved under the Public Health Service Act.

The relevant regulatory pathway for a conventional generic is an abbreviated new drug application, or ANDA, rather than a biosimilar application under section 351(k). A generic applicant would need to address listed patents and exclusivities through the Orange Book and make the applicable certification under 21 U.S.C. § 355(j).[4]

Regulatory issue	Pasireotide assessment
FDA product	Signifor
Active ingredient	Pasireotide diaspartate
Drug category	Synthetic somatostatin analogue peptide
Generic pathway	ANDA
Biosimilar pathway	Not applicable
Patent certification	Paragraph I, II, III, or IV depending on listed patent status
Relevant dosage forms	Immediate-release injection; separate analysis for LAR depot
Regulatory exclusivity	Separate from patent protection and dependent on indication and approval history

An Orange Book listing does not determine whether every claim is valid or infringed. It determines whether a listed patent can create a statutory obstacle to approval of an ANDA. A Paragraph IV certification can trigger patent litigation and, if suit is timely filed, a 30-month stay of approval under the Hatch-Waxman framework.[4]

Are there Paragraph IV challenges or generic litigation?

The claims provided do not establish whether an ANDA applicant has filed a Paragraph IV certification, whether Novartis has sued, or whether a settlement exists. Those facts must be established from FDA Orange Book records, FDA patent-listing updates, PACER, and the relevant district-court docket.

The legal risk from a Paragraph IV challenge would focus on four issues:

Whether the proposed generic contains tartaric acid.
Whether the product is a liquid formulation for parenteral administration.
Whether the active ingredient is pasireotide or another formula II compound.
Whether the proposed pH and salt form satisfy claims 2 through 5.

A generic applicant could pursue a formulation that avoids the narrow claims while challenging the broader claim 1 on validity grounds. Likely validity theories would include:

Anticipation by an earlier injectable somatostatin formulation;
Obviousness based on known peptide salts, acids, and pH conditions;
Lack of written description across the full formula II genus;
Lack of enablement for the full scope of the Markush claim;
Indefiniteness in terms such as "about" or the definition of formula II.

The patent holder would likely respond that the claimed tartaric-acid formulation solves a specific stability or solubility problem and that the formulation combination was not predictable from the prior art.

How strong is the patent estate?

The estate is strongest against a formulation that copies the commercial product architecture:

Pasireotide diaspartate;
Liquid injectable dosage form;
Tartaric acid;
Acidic pH near 4 to 4.5.

The estate is weaker against products that use:

A different acid or buffer;
A nonliquid or dry formulation;
A different delivery system;
A different somatostatin analogue;
A non-parenteral route;
A pH outside the claim 3 range.

Product strategy	Claim risk
Pasireotide diaspartate with tartaric acid, pH 4.2	High
Pasireotide free base with tartaric acid	Potentially high under claims 1 and 4
Pasireotide with citrate and no tartaric acid	Lower literal risk
Pasireotide lyophilized powder for reconstitution	Depends on whether the claimed liquid exists at the relevant infringement stage
Pasireotide depot microspheres	Lower risk under these claims; separate patents may apply
Different somatostatin analogue within formula II	Potentially covered by claim 1
Pasireotide oral formulation	Outside the express parenteral limitation

The patent's commercial durability depends heavily on the remaining term. Because it is a formulation patent rather than a foundational composition patent, its value declines sharply once a technically viable noninfringing formulation reaches the market.

What licensing and settlement issues matter?

A license covering pasireotide's active ingredient, a liquid formulation, or a long-acting delivery system may not automatically cover U.S. Patent 8,299,209. License diligence should identify:

Whether the license includes formulation patents;
Whether it covers U.S. ANDA rights;
Whether it includes settlement restrictions;
Whether it grants a date-certain generic launch;
Whether it covers Signifor injection, Signifor LAR, or both;
Whether it includes manufacturing know-how separate from patent rights.

No settlement agreement or licensing transaction should be attributed to this patent without a specific agreement, court filing, SEC disclosure, or regulatory record.

What geographic coverage does the patent provide?

U.S. Patent 8,299,209 provides rights only in the United States. Parallel protection may exist in foreign jurisdictions through the related international patent family, but each jurisdiction requires separate analysis of:

Granted claims;
National-phase status;
Supplementary protection certificates;
Patent-term adjustments;
Opposition or revocation proceedings;
Local claim construction;
Regulatory linkage rules.

A U.S. patent does not block manufacture or sale in Europe, Japan, Canada, or other markets unless a corresponding enforceable national patent exists.

Key Takeaways

U.S. Patent 8,299,209 is a formulation patent directed to tartaric-acid-containing liquid parenteral somatostatin analogue formulations.
Claims 4 and 5 specifically target pasireotide, with claim 5 directed to pasireotide in aspartate di-salt form.
Claim 1 is materially broader than the pasireotide-specific claims and may cover related somatostatin analogues within the formula II genus.
Claim 3 adds a pH range of approximately 4 to 4.5.
Signifor injection is the principal commercial product implicated by the claim set; Signifor LAR requires separate depot-formulation analysis.
Pasireotide is a small-molecule peptide drug subject to the ANDA pathway, not the biosimilar pathway.
A generic using pasireotide diaspartate, tartaric acid, and an acidic pH near 4.2 would present the highest infringement risk.
Substitution of the acidulant, a different dosage form, or a depot delivery system may reduce literal infringement risk.
The patent's nominal term appears to reach approximately 2026, subject to USPTO term-adjustment records.
Paragraph IV litigation, settlements, and Orange Book listing status require docket- and FDA-record-specific verification and cannot be determined from the claims alone.

FAQs

Can a generic avoid U.S. Patent 8,299,209 by using citrate instead of tartaric acid?

Potentially. Removing tartaric acid would avoid a core express limitation, but the product could still face equivalents arguments depending on the formulation's function, result, prosecution history, and differences from the patented formulation.

Does a pasireotide formulation infringe if it uses a different salt?

It may. Claim 5 requires the aspartate di-salt, but claim 4 covers pasireotide or a pharmaceutically acceptable salt thereof, and claim 1 covers free, salt, or protected forms within the formula II definition.

Does the patent cover pasireotide tablets?

No. The claims require a liquid formulation for parenteral administration. An oral tablet would not satisfy that express limitation.

Can a formulation outside pH 4 to 4.5 still infringe?

Yes. Claims 1, 2, 4, and 5 do not contain the pH limitation. A product outside the range in claim 3 could still fall within another asserted claim.

Is pasireotide eligible for a biosimilar application?

No. Pasireotide is regulated as a small-molecule drug for generic purposes. A competing product would generally use the ANDA pathway rather than a section 351(k) biosimilar application.

References

United States Patent and Trademark Office. (2012). U.S. Patent No. 8,299,209, liquid formulations of somatostatin analogues. U.S. Department of Commerce.
U.S. Food and Drug Administration. (2022). Signifor (pasireotide diaspartate) injection prescribing information. FDA.
United States Patent and Trademark Office. (n.d.). Patent term calculator and patent term adjustment guidance. U.S. Department of Commerce.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	0314695.8	Jun 24, 2003
United Kingdom	0325388.7	Oct 30, 2004

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1648934	⤷ Start Trial	PA2012016	Lithuania	⤷ Start Trial
European Patent Office	1648934	⤷ Start Trial	C20120019 00062	Estonia	⤷ Start Trial
European Patent Office	1648934	⤷ Start Trial	PA2012016,C1648934	Lithuania	⤷ Start Trial
Argentina	044852	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,299,209

Summary for Patent: 8,299,209