Patent: 10,413,593

Summary for Patent: 10,413,593

Title:	Co-agonists of the glucagon and GLP-1 receptors
Abstract:	Described are peptide analogs of glucagon, which have been modified to be resistant to cleavage and inactivation by dipeptidyl peptidase IV (DPP-IV) and to increase in vivo half-life of the peptide analog while enabling the peptide analog to have relatively balanced agonist activity at the glucagon-like peptide 1 (GLP-1) receptor and the glucagon (GCG) receptor, and the use of such GLP-1 receptor/GCG receptor co-agonists for treatment of metabolic disorders such as diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and obesity.
Inventor(s):	Bianchi; Elisabetta (Pomezia, IT), Carrington; Paul E. (South San Francisco, CA), Deng; Qiaolin (Edison, NJ), Nargund; Ravi (East Brunswick, NJ), Orvieto; Federica (Pomezia, IT), Palani; Anandan (Bridgewater, NJ), Pessi; Antonello (Rome, IT), Tucker; Thomas Joseph (North Wales, PA), Wu; Chengwei (Ambler, PA)
Assignee:	Merck Sharp & Dohme Corp. (Rahway, NJ)
Application Number:	15/519,565
Patent Claims:	see list of patent claims

Executive summary US Patent 10,413,593 is a composition-and-method patent family built around specific peptide sequences (SEQ ID NO: 7, 8, 10, 13, 17) and a defined fatty-acid–conjugated embodiment (SEQ ID NO:10 with a C16 fatty acid attached through a γE–γE spacer to the ε-amino group of a lysine). The claims cover (i) the peptides (including sodium salts), (ii) pharmaceutical compositions containing the peptides plus a carrier, (iii) combination compositions that further include insulin or specified insulin analogs, and (iv) treatment methods for diabetes (Type 1, Type 2, gestational) and obesity, including co-administration timing permutations. The enforceability and infringement risk hinge on whether a generic or biosimilar-equivalent product practices the claimed peptide sequences (and salt form) and, for combination/indication claims, includes insulin analogs within the specified list and uses the claimed therapeutic regimen.

What is US Patent 10,413,593 and what do its peptide claims cover?

US 10,413,593 claim scope is defined primarily by peptide sequence identity to named SEQ IDs, plus an optional but material structural limitation for one embodiment (SEQ ID NO:10).

Claim 1: peptides defined by SEQ ID NO 7/8/10/13/17

Independent claim 1: “A peptide, wherein the peptide has the amino acid sequence of SEQ ID NO: 7, 8, 10, 13, or 17, or a pharmaceutically acceptable salt thereof.”

Key points for claim construction and infringement:

• Sequence identity is the gatekeeper. A product must contain a peptide matching one of the listed sequences. Design-arounds that change any residue beyond allowable conservative variants are generally out of scope because the claim is sequence-specific (not functional).
• Salt coverage is explicit. “Pharmaceutically acceptable salt thereof” creates a category of salts; claims 2, 12, and 19 narrow to the sodium salt, raising enforceability for sodium-form commercial products.
• No delivery form limitation. Claim 1 is not limited to route, dose, particle form, or manufacturing method, so infringement risk attaches to the peptide substance itself and any dosage form containing it.

Claims 6–10: multiple single-sequence peptide claims

Claims 6–10 are effectively the same sequence restriction as claim 1 but separated per SEQ ID. This structure is common in patent estates to:

• simplify infringement analysis per sequence,
• strengthen validity by keeping separate statutory claim sets aligned with distinct embodiments,
• capture different candidate peptide analogs used across products.

Claim 11: SEQ ID NO:10 fatty-acid conjugate with defined chemistry and C-terminal amine

Claim 11 adds a detailed structural specification:

• peptide has the SEQ ID NO:10 sequence,
• D-serine at the position indicated (“s” is D-serine),
• lysine at position 10 has its ε-amino group conjugated to a C16 fatty acid,
• conjugation uses a γ-glutamic acid–γ-glutamic acid dipeptide (γE–γE) spacer,
• peptide has a C-terminal amine.

This is the most “chemical” claim in the set. It is also the most actionable for design-around:

• Conjugation length and spacer identity matter. Changing the fatty-acid chain length (not C16), removing or altering the γE–γE spacer, or changing the C-terminal functionality can be potential routes out of literal infringement.
• C-terminal amine is a limit. Many peptides are provided with other capping groups or modifications; products must match the C-terminal amine requirement to land cleanly within claim 11.

Claims 2, 12, 19: sodium salt specificity

• Claim 2: sodium salt for the peptides of claim 1.
• Claim 12: sodium salt for the peptide of claim 11.
• Claim 19: sodium salt for the peptide of claim 16 (composition peptide set; not sequence-specific here but is nested).

Sodium salts are usually selected for stability and manufacturability. A sodium salt commercial product increases infringement leverage because the claim is narrowed to a specific salt identity rather than a broad pharmaceutically acceptable salt category.

What compositions are claimed under US 10,413,593, and how does insulin combination coverage expand risk?

The composition claims move from the peptide to dosage-form compositions and combination formulations with insulin/insulin analogs.

Claims 3, 13, 16: peptide + pharmaceutically acceptable carrier

• Claim 3: composition comprises claim 1 peptide (or sodium salt) + carrier.
• Claim 13: composition comprises claim 11 peptide + carrier.
• Claim 16: composition comprises a peptide having sequence in SEQ ID 7/8/10/13/17 + carrier.

These cover essentially any pharmaceutical formulation that contains the claimed peptide(s) plus a carrier, without specifying excipients or formulation technology (e.g., no restriction on encapsulation, PEGylation, microspheres, infusion systems, etc.). That breadth generally increases the surface area for infringement.

Claims 4–5, 14–15, 17–18: combination compositions with insulin or specified insulin analogs

Claim 4: composition further comprises an insulin or insulin analog.
Claim 5: insulin analog comprises one of:

• insulin detemir
• insulin glargine
• insulin levemir
• insulin glulisine
• insulin lispro

Claims 14–15 and 17–18 repeat the same combination concept for the SEQ ID:10 embodiment and the general SEQ ID 7/8/10/13/17 peptide sets.

Commercial impact:

• Infringement can arise from co-formulation or co-dosing depending on how “composition” is interpreted under the patent’s claim language and the accused product’s physical presentation.
• If a competitor markets a regimen or kit that includes both (i) the claimed peptide formulation and (ii) an insulin analog matching the specified list, exposure rises materially for combination claims, especially if the products are administered as a combined composition in a single dosage form or as a packaged combination that is argued to be a single “composition.”

What method-of-treatment claims exist, and how do timing variants affect infringement?

Method claims cover both disease categories and co-administration timing structures.

Claims 20–26: administering claimed peptide composition with insulin/insulin analog composition

Claim 20: method for metabolic disease treatment with administration of the peptide composition of claim 16. Metabolic disease includes diabetes or obesity.

Claim 21 specifies diabetes subtypes: Type I, Type II, gestational.

Claim 22 adds a structured administration approach:

• (i) administer an effective amount of the peptide composition and administer an effective amount of an insulin/insulin analog composition, or
• (ii) administer both within the method body as recited.

Claim 23 introduces timing flexibility:

• peptide prior to insulin,
• insulin prior to peptide,
• same time.

Claim 24 repeats the insulin analog list (detemir/glargine/levemir/glulisine/lispro).
Claim 25 repeats diabetes subtypes.
Claim 26 adds sodium salt specificity.

Timing significance:

• Claim 23 is a major infringement facilitator. It does not require a particular lead/lag interval and explicitly includes “same time.”
• For design-arounds, the most practical route is often to avoid the insulin-analog combination scope (not merely alter the schedule), unless a product can argue it does not meet “composition” interpretation.

Claims 27–30: monotherapy method coverage for peptide

Claim 27: administering the peptide (claim 1) to treat metabolic disease (diabetes or obesity).
Claims 28–30: diabetes subtypes, diabetes-only, obesity-only.

This monotherapy coverage means a competitor cannot avoid infringement by not combining with insulin. Any product that uses the claimed peptide sequences for those indications can fall under method-of-use coverage.

How strong is the patent estate posture implied by claim breadth (sequence-defined + combination + methods)?

On the face of the claim set provided, the estate posture is strong for enforceability against:

• product substitutes that reproduce the exact peptide sequence (SEQ ID strictness),
• sodium salt formulations (narrow salt claims),
• any formulation containing the claimed peptides (carrier not restricted),
• combination regimens with specified insulin analogs (expanded clinical scenario coverage),
• both diabetes and obesity (two major metabolic indications in one patent set),
• timing-independent co-administration (claim 23).

The claims also reveal likely litigation focal points:

1. Sequence infringement: does the accused peptide match SEQ ID NO:7/8/10/13/17 exactly?
2. Salt form: is the product the sodium salt (claims 2/12/19/26)?
3. SEQ ID NO:10 structural features (claim 11): C16 fatty-acid conjugation via γE–γE spacer and C-terminal amine.
4. Insulin analog list match: does the combination include one of the specified analogs?
5. Indication and method performance: does the accused regimen meet diabetes/obesity treatment claims and follow the timing structure (or fall within the “prior”/“same time” options)?

What patents protect the same peptide/combination space around US 10,413,593?

A comprehensive landscape requires the full patent family and the associated claims of related applications, including continuation/divisional members and any subsequent US filings. Without those bibliographic identifiers and without the full text of the patent (including claim numbering, specification-defined terms, priority dates, assignee, and cited references), a reliable count of “how many patents cover” the same sequences, salts, insulin combinations, or formulation/manufacturing methods cannot be produced without risking factual error.

Therefore, no additional patent numbers or family members are provided here.

When does US 10,413,593 lose exclusivity, and what is the critical timeline?

Exclusivity loss depends on:

• earliest effective filing date,
• patent term adjustment and terminal disclaimers,
• whether any patent term extensions apply,
• status of related regulatory exclusivities and potential continuation effects.

Those determinations require the patent’s filing/priority data and term computation inputs, which are not included in the prompt. No exclusivity dates are stated here.

What are the likely generic entry risks if a competitor files an FDA application?

US 10,413,593 is not a conventional small-molecule patent profile. Based on the peptide-centric claim set and explicit insulin combination language, the enforcement risk to “generic entry” turns on whether the peptide is treated as:

• a chemically synthesized peptide with a small-molecule-like regulatory pathway (rare for complex peptide-drug conjugates),
• a biologic (where “generic” is replaced by biosimilar-style development),
• a combination product with insulin, changing the regulatory and exclusivity framework.

However, without the drug identity linked to the patent, its FDA approval status, and the product’s regulatory classification, a “Paragraph IV” or biosimilar-specific risk mapping cannot be generated without factual fabrication.

No regulatory pathway assertions are made here.

What Orange Book status would matter for US 10,413,593?

Orange Book status depends on whether the underlying drug is listed there, the application type (NDA), and whether the listed patent(s) correspond to the exact active ingredient and dosage form. The prompt does not provide the NDA/ANDA identifiers, Orange Book listing numbers, or product name.

No Orange Book listing mapping is provided here.

Which companies are challenging or licensing the claims in US 10,413,593?

Company challenge and licensing analysis depends on:

• lawsuit dockets (Paragraph IV, declaratory judgment, injunction),
• assignment/ownership changes,
• published licenses or settlements.

No litigation or licensing party data is provided in the prompt.

No named parties are provided.

How does SEQ ID NO:10 chemistry change infringement analysis vs. other sequences?

Claim 11 introduces a conjugate architecture that can materially differentiate infringement risk between:

• SEQ ID–only claims (claims 1, 6–10, 16 and downstream),
• vs. SEQ ID NO:10 plus specific conjugation parameters (claim 11).

Practical interpretation:

• An accused product that matches SEQ ID NO:10 sequence but uses a different fatty-acid chain length or different spacer can evade claim 11 but still potentially infringe sequence-defined claims if those sequence claims are not tied to the conjugation chemistry.
• Conversely, a product that matches the conjugation chemistry but changes a residue in the peptide sequence may miss both claim 1/6–10 sequence coverage and claim 11.

The most robust enforceability is typically where both sequence and structural feature claims can be asserted in parallel.

Key Takeaways

• Core protection is sequence identity. Claims 1 and 6–10 cover peptides that match SEQ ID NO: 7, 8, 10, 13, or 17, including pharmaceutically acceptable salts.
• Sodium salts are specifically captured. Claims 2, 12, 19 and downstream sodium-salt method limitations tighten infringement leverage for sodium-form products.
• SEQ ID NO:10 has a detailed conjugate limitation. Claim 11 requires a C16 fatty-acid conjugate via a γE–γE spacer and a C-terminal amine, creating a chemistry-based infringement and design-around battleground.
• Combination coverage is broad for insulin analogs. Claims 4–5, 14–15, and 17–18 cover insulin or specified insulin analogs (detemir, glargine, levemir, glulisine, lispro).
• Method claims cover diabetes and obesity and are timing-flexible. Claims 20–26 include co-administration order permutations (prior, prior, or same time).
• Without bibliographic metadata and FDA/regulatory identifiers, the broader patent-family and exclusivity timeline cannot be stated without risking errors.

FAQs

1. If a competitor uses a non-sodium salt of the same peptide, which claims still apply?
2. Can a product evade claim 11 by changing the fatty-acid chain length away from C16 while keeping SEQ ID NO:10?
3. Does the co-administration timing limitation in claim 23 require a specific dosing interval to infringe?
4. How do the insulin analog list constraints in claims 5/15/18 shape infringement risk for combinations using other insulin types?
5. If a therapy uses the claimed peptide for obesity but not diabetes, which method claims are implicated?

References

No external sources were used or cited because no patent bibliographic identifiers, FDA identifiers, Orange Book listings, or litigation records were provided in the prompt.

Details for Patent 10,413,593

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	HUMALOG	insulin lispro	Injection	020563	June 14, 1996		2035-10-22
Eli Lilly And Company	HUMALOG	insulin lispro	Injection	020563	August 06, 1998		2035-10-22
Eli Lilly And Company	HUMALOG	insulin lispro	Injection	020563	September 06, 2007		2035-10-22
Eli Lilly And Company	HUMALOG	insulin lispro	Injection	020563	June 06, 2017		2035-10-22
Eli Lilly And Company	HUMALOG	insulin lispro	Injection	020563	November 15, 2019		2035-10-22
Sanofi-aventis U.s. Llc	LANTUS	insulin glargine	Injection	021081	April 20, 2000		2035-10-22