Patent: 6,056,957

Summary for Patent: 6,056,957

Title:	Humanized monoclonal antibodies against human interleukin-5
Abstract:	A monoclonal antibody is provided which specifically binds to human interleukin-5. Also provided are a hybridoma which produces the monoclonal antibody; complementary DNAs which encode the heavy and light chain variable regions of the monoclonal antibody and CDRs therefrom; humanized monoclonal antibodies; and pharmaceutical compositions comprising the monoclonal antibody or anti-idiotypic antibodies directed against it, humanized monoclonal antibodies, binding fragments, binding compositions or single-chain binding proteins derived from the antibody and a physiologically acceptable carrier.
Inventor(s):	Chou; Chuan-Chu (Westfield, NJ), Murgolo; Nicholas J. (Millington, NJ), Abrams; John S. (Belmont, CA), Jenh; Chung-Her (Edison, NJ), Petro; Mary E. (Green Pond, NJ), Silver; Jon E. (San Jose, CA), Tindall; Stephen (Madison, NJ), Windsor; William T. (East Brunswick, NJ), Zavodny; Paul J. (Mountainside, NJ)
Assignee:	Schering Corporation (Kenilworth, NJ)
Application Number:	08/284,516
Patent Claims:	see list of patent claims

Executive summary: US Patent 6,056,957 claims anti–human interleukin-5 (IL-5) binding antibodies defined by specific heavy/light variable regions (SEQ ID NOs: 1 and 2) and downstream IP layers for: hybridomas, recombinant expression (DNA, vectors, host cells, manufacturing), binding compositions (variable-region polypeptides), and humanized antibodies with specified CDRs and “mature” variable-region sequences (SEQ ID NOs 36, 37, 40, 41, 46, 47, 56, 57, 64, 65). The estate is structurally broad at the antigen-binding level but narrowed by hard sequence definitions, limiting design-around through alternative IL-5 binders. Competitive risk concentrates on whether later IL-5 antibodies use variable regions/CTRs (and exact humanized mature sequences) outside these enumerated sets, and whether prosecution estoppel or scope limits reduce coverage over variants.

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United States Patent 6,056,957 claims and scope analysis for anti-IL-5 monoclonal antibodies

US 6,056,957 is drafted as a layered antibody patent with claims that run from “anchor sequences” (SEQ ID NO: 1 and 2) into humanized variants and into expression and pharmaceutical-composition coverage. Claim scope is primarily defined by variable-region amino-acid sequences and by CDRs derived from those variable regions.

What are the claim “anchors” that define infringement risk?

• Original binding antibody anchor:
  • Heavy chain variable region: SEQ ID NO: 1
  • Light chain variable region: SEQ ID NO: 2
• Humanized binding antibody anchor:
  • Humanized antibody has CDRs from the anchor monoclonal and includes specific “mature” variable-region sequences:
    • Heavy: SEQ ID NOs 36, 40, 46, 56, 64
    • Light: SEQ ID NOs 37, 41, 47, 57, 65
• Direct binding composition anchor:
  • Polypeptides containing SEQ ID NO: 1 and/or 2
  • Humanized variable-region polypeptides containing the enumerated mature sequences

How broad is the claim language in practice?

• Broad in “claim category” (antibody, fragment, hybridoma, binding protein/composition, DNA/vector/host cell, method of making, pharmaceutical formulation).
• Narrow in “defining feature”: exact SEQ ID NO-tied amino-acid variable regions and CDR sets. This is a classic “sequence-locked” structure: it can capture variants if they still match the enumerated sequences/regions, but it gives clear off-ramps for competitors to move outside those sequences.

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What patents protect binding to human IL-5 using heavy chain SEQ ID NO 1 and light chain SEQ ID NO 2?

Claim 1: antibody or fragment with exact variable regions

• Claim 1 covers a monoclonal antibody or fragment binding human IL-5 with:
  • Heavy variable region SEQ ID NO: 1 and/or
  • Light variable region SEQ ID NO: 2
• The “and/or” structure creates a practical breadth issue: infringement may be possible if only one chain variable region matches the enumerated SEQ ID, assuming the other chain still yields binding and the claim interpretation accepts “fragment” embodiments.

Claim 3 to 5: binding composition using SEQ ID–defined variable-region polypeptides

• Claim 3: polypeptide comprising amino acid sequence defined by SEQ ID NO: 1 or 2
• Claims 4 and 5 lock to individual chains:
  • Claim 4: polypeptide comprises SEQ ID NO: 1
  • Claim 5: polypeptide comprises SEQ ID NO: 2
• This matters because it can capture non-antibody “binding proteins” that still use the variable-region polypeptide sequences.

Claim 29: composition containing both SEQ ID NO 1 and 2

• Claim 29 explicitly covers polypeptides comprising both sequences, strengthening coverage against products that retain both variable regions.

Business impact

If a generic, biosimilar, or next-gen IL-5 binder is built on variable regions matching these SEQ ID sets, the patent is positioned to capture:

• antibody formulations,
• fragments (depending on how “fragment” is construed),
• recombinant constructs expressing those variable sequences,
• and variable-region polypeptide binding products.

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How do hybridoma claims in US 6,056,957 expand enforceable coverage?

Claim 2: hybridoma secreting the antibody

• Covers a hybridoma secreting the IL-5–binding monoclonal with:
  • Heavy variable region SEQ ID NO: 1 and/or
  • Light variable region SEQ ID NO: 2

Litigation leverage from hybridoma claims

Hybridoma claims can be powerful in proving:

• biological source identity,
• lineage and deposit linkage,
• and manufacturing-origin arguments in infringement discovery.

In practice, however, modern commercial production often uses recombinant expression rather than maintaining the original hybridoma as the commercial manufacturing source. Still, claim 2 can help in establishing chain-of-derivation facts and can complement DNA/vector/host-cell claims.

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What manufacturing and genetic engineering claims exist in US 6,056,957 (DNA, vector, host cell, method of making)?

US 6,056,957 includes a full IP “stack” on expression and production.

DNA and genetic constructs

• Claim 6: isolated DNA encoding SEQ ID NO: 1 or 2
• Claims 7-10: isolated DNA encoding the specific chain sequences:
  • Claim 7/8: DNA encoding SEQ ID NO: 1 (including a nucleotide sequence defined by SEQ ID NO: 1)
  • Claim 9/10: DNA encoding SEQ ID NO: 2 (including a nucleotide sequence defined by SEQ ID NO: 2)
• Claim 11: recombinant vector comprising that DNA

Host cell and production method

• Claim 12: host cell comprising the recombinant vector
• Claim 13: method of making polypeptide by culturing the host cell under expression conditions

Claim 25: production method for humanized sequences

• Claim 22 provides DNA encoding the enumerated “mature” humanized sequences
• Claims 23-25 mirror the recombinant production stack:
  • recombinant vector (claim 23)
  • host cell (claim 24)
  • method of making (claim 25)

Business impact

Even if a competitor redesigns delivery format or formulation, the patent can still target:

• expression constructs,
• cell lines, and
• manufacturing steps that require the patented sequences.

Design-around tends to focus on changing the variable-region sequences such that they no longer match the enumerated SEQ ID sets while retaining IL-5 binding via different CDRs/frameworks.

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What patents cover humanized IL-5 antibodies and CDR-derived binding proteins in US 6,056,957?

Claim 14: humanized antibody with CDRs derived from anchor monoclonal

• Humanized monoclonal antibody binding human IL-5 comprising complementarity determining regions from the heavy and light variable regions of the monoclonal antibody of claim 1.

This is a key “bridging” claim:

• It keeps coverage tied to humanization based on the anchor CDRs.
• It can capture a range of humanization frameworks so long as CDRs remain derived from the anchor variable regions and/or the mature sequences match the later locked claims.

Claims 15-20: humanized antibodies with enumerated mature variable sequences

• Claim 15: humanized antibody comprising heavy or light chain variable region comprising a mature amino acid sequence set forth in SEQ ID NOs 36, 37, 40, 41, 46, 47, 56, 57, 64 or 65
• Claims 16-20 specify combinations:
  • Claim 16: heavy SEQ ID NO: 36 + light SEQ ID NO: 37
  • Claim 17: heavy SEQ ID NO: 40 + light SEQ ID NO: 41
  • Claim 18: heavy SEQ ID NO: 46 + light SEQ ID NO: 47
  • Claim 19: heavy SEQ ID NO: 56 + light SEQ ID NO: 57
  • Claim 20: heavy SEQ ID NO: 64 + light SEQ ID NO: 65

Claim 21: binding composition with humanized mature variable sequences

• Covers polypeptide comprising a variable region of the humanized antibody containing mature amino acid sequences 36, 37, 40, 41, 46, 47, 56, 57, 64 or 65.

Claim 27-28: IL-5 binding protein and single-chain binding protein

• Claim 27: IL-5 binding protein comprising CDRs from heavy and/or light variable regions of claim 1 monoclonal
• Claim 28: IL-5 binding protein is a single chain IL-5 binding protein

Business impact

This category reduces the chance that a competitor can avoid infringement solely by moving from full-length IgG to:

• scFv-like constructs,
• CDR-containing binding proteins,
• or alternative antibody formats, so long as the CDRs or the enumerated mature variable sequences remain in-scope.

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What formulations are protected by US 6,056,957 (pharmaceutical composition claim)?

Claim 26: pharmaceutical composition

• A pharmaceutical composition comprising the humanized monoclonal antibody of claim 14 plus a pharmaceutically acceptable carrier.

The formulation claim is broad in carrier choice but narrow in requiring the claimed humanized antibody.

Business impact

The claim is mainly a coverage bridge for:

• product formulations containing the claimed humanized antibody,
• including typical IL-5 therapeutic delivery forms (liquid/injectable formulations), assuming they include the covered antibody.

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How many claim layers does US 6,056,957 add, and what does that mean for design-around?

High-level claim-layer map

1. Antibody/fragment binding (claim 1)
2. Hybridoma source (claim 2)
3. Binding compositions with SEQ IDs (claims 3-5, 29)
4. Nucleic acids (claims 6-11, 22-23)
5. Expression system (host cell + vector) (claims 11-12, 23-24)
6. Manufacturing method (claims 13, 25)
7. Humanized antibody via CDR derivation and/or mature sequences (claims 14-20, 21)
8. Binding proteins including single-chain formats (claims 27-28)
9. Pharmaceutical composition containing the humanized antibody (claim 26)

Design-around implications

• If a competitor keeps binding to IL-5 but changes variable regions so they no longer match the specific SEQ ID sets, claims anchored to those sequences can be avoided.
• If a competitor humanizes but uses CDRs not derived from the anchor sequences, claim 14/27 pathways weaken.
• The enumerated “mature” sequence combinations (claims 15-20) create a finite set of in-scope humanized variants, which can be a roadmap for a freedom-to-operate (FTO) assessment.

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When does US 6,056,957 lose exclusivity, and how do filing-date rules affect it?

No expiration date can be stated from the claim text alone. Without prosecution history, application and patent filing dates, and any adjustments/extensions, exclusivity timing for US 6,056,957 cannot be determined from the provided information.

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What is the Orange Book status of US 6,056,957?

US 6,056,957 is a monoclonal antibody patent. Orange Book exclusivity listings typically map to FDA-approved drug products with active ingredients that are small molecules. Patent-by-patent listing depends on whether the associated product is an FDA-approved biological licensed via BLA and whether the patent is listed in the appropriate FDA patent listing system.

No product mapping between US 6,056,957 and a specific marketed biologic is provided here, so Orange Book/BLA listing status cannot be stated from the supplied inputs.

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What generic or biosimilar entry risks exist for IL-5 binders covered by US 6,056,957?

Generic (ANDA) vs biosimilar (BLA) risk framing

• US 6,056,957 is not positioned for ANDA-style small-molecule generic substitution.
• The enforcement and entry risk profile aligns with biosimilar development:
  • biosimilar must be highly similar to a reference IL-5 antibody product,
  • but it can use sequence changes if it still meets biosimilarity requirements.
• The hard sequence locks in claims 1-2 and 15-20 increase the chance that a biosimilar using different humanized sequences avoids direct literal infringement.

Practical entry risk factors

• Whether a potential entrant’s variable-region sequences match the enumerated SEQ ID sets.
• Whether CDRs are derived from the anchor antibody variable regions in a manner captured by claim 14/27.
• Whether manufacturing constructs (DNA/vector/host cell) are built around the same sequences.

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What patent litigation affects US 6,056,957 and the IL-5 antibody space?

No litigation history, case caption, parties, or settlements are provided. Patent landscape impact from enforcement actions cannot be concluded from the supplied information.

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How strong is the patent estate around US 6,056,957 for anti-IL-5 assets?

Strength signals from claim structure:

• The patent covers multiple functional layers that usually occur in antibody programs: variable-region sequences, humanization, recombinant production, and formulations.
• The presence of “mature sequence” enumerations in humanized claims indicates the patentee anticipated specific follow-on sequences and locked them in.

Weakness signals that matter for later entrants:

• Coverage is heavily tied to exact SEQ ID enumerations. Competitors that select different variable sequences reduce literal infringement risk.
• If humanization frameworks are altered such that the resulting “mature” sequences fall outside enumerated combinations, claim 15-20 may not read on the new product.

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Competitive landscape: how do next-gen IL-5 antibodies compare with this sequence-locked claim set?

Without identifying the marketed IL-5 antibody(s) and mapping those products’ sequences to the SEQ IDs in US 6,056,957, direct competitive comparisons cannot be responsibly made from the provided information.

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Key Takeaways

• US 6,056,957 is a sequence-locked anti-IL-5 antibody patent with a full recombinant-manufacturing and humanization stack.
• The core infringement question is whether the accused antibody (or scFv/IL-5 binding protein variant) uses heavy/light variable-region amino-acid sequences matching SEQ ID NO: 1/2 and/or the enumerated humanized “mature” sequences 36/37, 40/41, 46/47, 56/57, 64/65.
• Claims extend coverage beyond full antibodies into binding polypeptides/proteins, recombinant vectors/host cells, and pharmaceutical compositions containing the claimed humanized antibody.
• Design-around is primarily achieved by selecting different variable regions such that the sequences and enumerated humanized mature sequences fall outside the claim-defined sets, and by choosing CDRs that do not derive from the anchor variable regions.

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FAQs

1. Can scFv or other IL-5 binding proteins infringe US 6,056,957?
Yes, claim 27-28 target IL-5 binding proteins with CDRs from the anchor variable regions, and claim 21 covers humanized variable-region polypeptides containing enumerated mature sequences.

2. Do humanized frameworks automatically avoid infringement?
No. Claim 14 depends on humanization with CDRs derived from the anchor monoclonal. Claims 15-20 also depend on specific enumerated mature sequences.

3. What is the biggest literal infringement risk point for a competitor?
Using variable-region amino-acid sequences that match the enumerated SEQ ID NOs in claim 1/3-5/29 and the humanized mature sequences in claims 15-20/21.

4. Can manufacturing-only activity infringe even without marketing the antibody?
Yes. Claims 11-13 and 23-25 cover recombinant vectors, host cells, and methods of making the polypeptides under expression conditions.

5. How does “and/or” in the heavy/light variable claims change risk?
Claim 1’s “SEQ ID NO: 1 and/or SEQ ID NO: 2” can broaden coverage if either chain variable region matches while the antibody fragment still meets the binding definition for IL-5.

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References

1. United States Patent 6,056,957. (n.d.). Claims provided in prompt.

Details for Patent 6,056,957

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Teva Respiratory, Llc	CINQAIR	reslizumab	Injection	761033	23-Mar-16	6,056,957	2014-08-04