Patent: 10,119,132

Summary for Patent: 10,119,132

Title:	Long-acting coagulation factors and methods of producing same
Abstract:	Polypeptides comprising at least one carboxy-terminal peptide (CTP) of chorionic gonadotrophin attached to the carboxy terminus but not to the amino terminus of a coagulation factor and polynucleotides encoding the same are disclosed. Pharmaceutical compositions comprising the polypeptides and polynucleotides of the invention and methods of using and producing same are also disclosed.
Inventor(s):	Fima; Udi Eyal (Dvira, IL), Hart; Gili (Shoham, IL)
Assignee:	OPKO Biologics Ltd. (Kiryat Gat, IL)
Application Number:	14/948,890
Patent Claims:	see list of patent claims

United States Patent 10,119,132: What the Claims Actually Cover and Where the Landscape Concentrates

U.S. Patent 10,119,132 claims a treatment method for hemophilia A and hemophilia B that uses CTP-modified coagulation factors: Factor VII (FVII) or Factor IX (FIX) with three chorionic gonadotropin carboxy terminal peptides (CTPs) attached to the carboxy terminus. The claims narrow further with defined CTP sequences (SEQ ID NO: 1, 2), optional glycosylation, optional linkers (including peptide bonds), optional selection of overall construct sequence sets (SEQ ID NO: 25, 46 for FVII; SEQ ID NO: 31, 48 for FIX), and administration specifics including subcutaneous dosing and forms of FVIIa/FIXa (including disulfide-linked two-chain heterodimers) and human child subjects.

From a landscape standpoint, the patent’s enforceable core is not “gene therapy” or “replacement factor” in general. It is a very specific chimera concept: (i) a coagulation factor carrier (FVII/FIX, optionally activated forms), (ii) with exactly three CTPs at the C-terminus of that carrier, and (iii) with specific claim-dependent refinements that align with a defined molecular series rather than a broad functional claim.

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What are the claim elements that create the enforceable core?

1) Does the patent claim treatment by “CTP fusion” or by “any CTP-containing factor”?

The independent claim language requires a CTP-modified Factor VII for hemophilia A and a CTP-modified Factor IX for hemophilia B, where the construct is defined as:

• Coagulation Factor VII polypeptide + three CTPs attached to the carboxy terminus (hemophilia A)
• Coagulation Factor IX polypeptide + three CTPs attached to the carboxy terminus (hemophilia B)

The “three CTPs” and “attached to the carboxy terminus” limitations are structural and operate as claim-differentiating boundaries. The claims are not limited to a single CTP implementation unless the dependent claims choose particular SEQ ID NO: 1/2.

2) What is the molecular scope if a competitor uses a different number of CTPs or attaches them elsewhere?

The claims explicitly require three CTPs. A design that uses:

• two CTPs,
• four CTPs, or
• CTPs attached at an internal position rather than the carboxy terminus,
  would miss the literal structural requirement.

Even if such a variant has comparable pharmacokinetics, the claims as provided are not functional in the independent claim (they do not claim “CTP-containing to extend half-life”); they claim a defined construct architecture.

3) How much room exists if the CTP sequences change?

Dependent claim 2/13 restricts at least one CTP to amino acid sequences selected from SEQ ID NO: 1 and SEQ ID NO: 2. The independent claim does not force that specific pair, but the dependent claims create layered scope. That matters because, in infringement analysis, a defendant can try to:

• use different CTP sequences to avoid dependent claim features, or
• design around by arguing that the independent claim is not satisfied if the CTP definition (as understood in the patent) requires those specific sequences.

4) How narrow is the “activated two-chain heterodimer” requirement?

Claims 7-8 and 18-19 add optional limitations:

• FVIIa or FIXa polypeptides, and specifically disulfide-linked two-chain heterodimer forms.
  If a competitor uses a different activation state or a different molecular assembly (for example, non-heterodimer forms), those dependent claims may not read on the product.

5) What is the dosing and patient-population limitation?

Claims 9-10 and 20-21 constrain:

• human child, and
• subcutaneous route.

Even if the composition is the same, a competitor using adult-only populations or another route (intravenous) can create claim-avoidance against these dependent claim limitations.

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Claim-by-claim: what each addition changes for infringement risk

Hemophilia A (Method; FVII-CTP)

• Claim 1 (independent): method of treating hemophilia A with CTP-modified FVII; requires three CTPs at the C-terminus.
• Claim 2: at least one CTP has SEQ ID NO: 1 or 2.
• Claim 3: at least one CTP is glycosylated.
• Claim 4-5: at least one CTP attached via linker, with peptide bond in claim 5.
• Claim 6: overall construct sequence is selected from SEQ ID NO: 25 or 46.
• Claim 7-8: FVIIa and specifically disulfide-linked two-chain heterodimer form.
• Claim 9: subject is human child.
• Claim 10: administering via subcutaneous route.

Hemophilia B (Method; FIX-CTP)

• Claim 11 (independent): method of treating hemophilia B with CTP-modified FIX; requires three CTPs at the C-terminus.
• Claim 12: overall construct sequence selected from SEQ ID NO: 31 or 48.
• Claim 13: at least one CTP is SEQ ID NO: 1 or 2.
• Claim 14: at least one CTP is glycosylated.
• Claim 15: at least one CTP is truncated.
• Claim 16-17: attached via linker, with peptide bond in claim 17.
• Claim 18-19: FIXa and specifically disulfide-linked two-chain heterodimer form.
• Claim 20: subject is human child.
• Claim 21: administering via subcutaneous route.

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Where the landscape pressure will concentrate

1) The competitive question: “CTP fusions to FVII/FIX” vs “CTP fusions to something else”

If another developer uses:

• CTPs attached to a different coagulation protein, or
• attaches to a non-coagulation carrier,
  then this patent’s independent claims (as provided) should not read, because they require FVII for A and FIX for B.

2) The critical similarity test: “three CTPs at the carboxy terminus”

Most design-around strategies will pivot on the structural anchor:

• three CTPs, and
• CTP attachment at the carrier’s carboxy terminus.

Any attempt to preserve pharmacology while changing this architecture will likely be the difference between (a) clean non-infringement and (b) an adverse “all-elements” match.

3) The “SEQ ID” dependent claims set up product-level mapping

Claim 6 for A and claim 12 for B use defined construct sequences:

• FVII series: SEQ ID NO: 25 and 46
• FIX series: SEQ ID NO: 31 and 48

This matters because product developers often disclose the exact amino acid constructs in manufacturing and regulatory filings. If those constructs align with these SEQ IDs, then the dependent claims become much harder to avoid.

4) Glycosylation and truncation are not cosmetic in claim terms

Claims 3 and 14 (glycosylated CTPs) and claim 15 (truncated CTP) are explicit. If a competitor manufactures CTP variants with non-glycosylated versions, or deliberately uses non-truncated CTP lengths, they may avoid those dependents. The independent claim may still be at issue, depending on how the patent defines “CTP” beyond the SEQ IDs.

5) Subcutaneous dosing and pediatric limitation create a second infringement lane

Claims 10 and 21 target subcutaneous administration, and claims 9 and 20 target human children. If a product is administered subcutaneously in pediatrics, these dependents are exposed. If a product is adult-focused initially, or dosed intravenously, those dependents can be avoided while leaving the independent claim as the main risk.

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Freedom-to-operate framing: which elements must be matched for an adverse outcome

Minimum coverage to meet the independent claims

To fall into the independent claim as written:

• Hemophilia A: administer a CTP-modified FVII polypeptide with three CTPs at the carboxy terminus.
• Hemophilia B: administer a CTP-modified FIX polypeptide with three CTPs at the carboxy terminus.

Everything else (SEQ IDs, glycosylation, linkers, activation state, heterodimer form, pediatric, route) is dependent layering.

Most likely product-specific risk drivers

The highest-probability infringement triggers in real-world cases are:

• the exact construct sequence matching a listed SEQ ID in dependent claims,
• the use of glycosylation on at least one CTP,
• peptide bond linkage mechanics at the CTP attachment site,
• use of the activated two-chain heterodimer forms (FVIIa/FIXa), and
• use of subcutaneous administration in human children.

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Critical assessment of patent strength based on claim drafting

1) Strength: clear structural limitations

The independent claims do not read like broad genus “CTP-conjugates.” They require:

• a specific coagulation factor (FVII or FIX),
• a defined CTP count (three),
• and CTP attachment location (carboxy terminus).

That is the kind of drafting that makes infringement analysis element-by-element and reduces the risk that “any improvement in PK” is automatically captured.

2) Weakness/defense: architecture is the hinge

Because the independent claims require three CTPs at a defined location, competitors can plausibly design around by:

• altering CTP number or attachment site, or
• using alternative attachment chemistries that break how the claim defines “attached to the carboxy terminus.”

Those strategies might reduce infringement exposure, even if pharmacology remains similar.

3) Enforceability depends on claim interpretation around “CTP”

Dependent claims use concrete SEQ ID numbers and specify glycosylation, truncation, and linker. The meaning of “CTP” in the independent claim, as construed in the patent specification, will determine how much freedom a competitor has to vary CTP sequences while still arguing non-infringement.

Given the multiple dependent constraints, the patent likely treats CTP as a definable moiety with sequence-specific meaning, which generally narrows what counts as the claimed “CTP-modified” construct.

4) Treatment claims reduce some common obviousness patterns

Method claims tied to a specific administered construct can complicate prior art mapping because the prior art must show not only a composition but its use for the claimed indication via the claimed construct architecture.

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What to watch in the US patent landscape around hemophilia A/B with CTP-fusions

Landscape nodes that usually determine market exclusivity

Even without enumerating each family member here, the market architecture typically breaks down into:

• Composition of matter filings for the CTP-fused constructs,
• Method-of-use claims for hemophilia indications (A and B),
• Claims focused on route of administration (subcutaneous),
• Claims focused on patient subsets (pediatrics),
• Claims tied to activated forms and molecular assemblies.

This patent is positioned primarily as a method-of-treatment layer. Its litigation leverage tends to be strongest when:

• the accused product is a close sequence match to the patented SEQ ID constructs, and
• administration matches claimed routes and patient populations.

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Key Takeaways

• U.S. Patent 10,119,132 centers on CTP-fused coagulation factors for hemophilia A (FVII) and B (FIX) with a hard structural requirement: three CTPs attached to the carrier’s carboxy terminus.
• The independent claims are architecture-driven, while dependent claims add product-level and use-level constraints: SEQ ID-defined constructs, glycosylation/truncation, linker mechanics, FVIIa/FIXa two-chain heterodimer forms, subcutaneous dosing, and human child populations.
• The enforceability profile is strongest against products that match the exact construct sequences and administration pattern. Design-around efforts will most likely target the hinge elements: CTP count and attachment position, followed by differences in CTP sequences and CTP post-processing (glycosylation/truncation).
• For investment and R&D decisions, the immediate action item is to map any candidate molecule’s sequence, attachment site, CTP number, and intended administration route/population to the specific claim elements above, because most defenses are element-specific rather than broad.

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FAQs

1) What is the single most important structural requirement in U.S. Patent 10,119,132?

The construct must be a CTP-modified coagulation factor where three CTPs attach to the carboxy terminus of FVII (hemophilia A) or FIX (hemophilia B).

2) Can a product avoid infringement by changing CTP sequences?

Changing CTP sequences may avoid dependent claim coverage (SEQ ID-based features), but the independent claims still require “CTP-modified” architecture with three CTPs at the carboxy terminus. Avoidance depends on how “CTP” is construed in the patent and whether the independent definition requires the specific sequences.

3) What do claims about glycosylation and truncation do in practice?

They add narrow dependent coverage. A developer that keeps the main architecture but removes glycosylation or avoids truncation can potentially avoid those dependent claims, though the independent claims may still remain.

4) Does the patent require activated FVIIa/FIXa?

Not in the independent claims as provided. Claims 7-8 (FVIIa) and 18-19 (FIXa) are dependent layers, so the independent infringement risk mainly turns on the CTP attachment architecture.

5) Why are subcutaneous administration and “human child” claims relevant to product strategy?

They define method coverage in specific use contexts. A company using a different route and/or treating adults first can reduce exposure to those dependent claims, leaving the independent construct-based claims as the primary risk line.

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References

[1] United States Patent 10,119,132. (claims excerpt as provided by user).

Details for Patent 10,119,132

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	January 15, 1974	10,119,132	2035-11-23
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	December 27, 1984	10,119,132	2035-11-23
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	February 15, 1985	10,119,132	2035-11-23
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	February 16, 1990	10,119,132	2035-11-23