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United States Patent 10,442,858: CD47 Antibody (SEQ ID 4/6 and SEQ ID 24/26) for Cancer Treatment

What does US 10,442,858 claim, at the method level?

US 10,442,858 is drafted as a “method of treating cancer” patent built around a narrow, sequence-defined anti-human CD47 monoclonal antibody and functional specifications tied to CD47 biology. The claims split into two parallel claim sets that differ by the exact antibody sequence pairs recited:

Claim set A (SEQ ID NO: 4/6 plus wild-type human IgG4 constant region):

Claim 1 (core): Treat cancer in a subject with an isolated monoclonal antibody that binds human CD47.
- Heavy chain variable (VH): SEQ ID NO: 4
- Light chain variable (VL): SEQ ID NO: 6
- Heavy chain constant: “wild-type human IgG4” heavy chain constant region
- VH/VL + WT IgG4 constant are explicit requirements, not optional.

Claim set B (SEQ ID NO: 24/26):

Claim 29 (core): Same overall structure, but with different sequence-defined VH/VL:
- Heavy chain: SEQ ID NO: 24
- Light chain: SEQ ID NO: 26
- No explicit IgG4 constant requirement appears in Claim 29 as provided, but later claims focus on antibody composition and the same functional limitations.

Both claim sets then layer on (i) SIRPα interaction blockade and (ii) hemagglutination phenotype constraints, followed by (iii) combination therapy exemplars and (iv) broad cancer class coverage (hematologic and solid tumors, with long enumerations).

What are the core technical requirements (and where they create real scope limits)?

The patent’s enforceable technical “center of gravity” is a sequence-defined antibody with human CD47 binding and a specific antibody architecture.

Core antibody definition

Claim	Antibody must bind human CD47	VH (sequence)	VL (sequence)	Constant / other
1	Yes	SEQ ID NO: 4	SEQ ID NO: 6	Wild-type human IgG4 heavy chain constant region (explicit)
29	Yes	SEQ ID NO: 24	SEQ ID NO: 26	Not specified in the excerpted Claim 29 text as provided

Core functional requirements (dependent claim posture, but critical)

Claim	Functional requirement	Scope effect
2 / 30	Antibody inhibits interaction between human CD47 and SIRPα	Narrows to pathway-blocking anti-CD47 rather than purely binding
3 / 31	Antibody does not cause significant or detectable hemagglutination vs a reference CD47 mAb that causes hemagglutination	Adds an important “safety/efficacy phenotype” qualifier tied to red blood cell reactivity

Add-on binding and “format” limitations

Human antibody requirement appears in both sets (Claim 4 / 32).
Kappa constant region appears only in Claim 5-7 for claim set A:
- Claim 5: human kappa constant region
- Claim 6: human kappa constant comprises SEQ ID NO: 22
- Claim 7: IgG4 heavy chain constant comprises SEQ ID NO: 20

For claim set B, the excerpted claim text focuses on VH/VL sequences (SEQ ID 24/26) and doesn’t add the constant-region sequence constraints in the same way.

Business implication: the broadest “landing zone” for freedom-to-operate (FTO) is not “anti-CD47 broadly,” but whether a competitor’s antibody matches the VH/VL sequences and (for Claim 1) the IgG4 heavy constant and (for Claim 5-7) the kappa constant and IgG4 constant sequence.

What is covered beyond the antibody itself: combinations, routes, and tumor breadth?

The claims use a layered structure: antibody identity first, then administration and combination therapy, then expanded tumor-type coverage.

Combination therapy examples (opsonization and chemotherapeutics)

Claim 8 (or 33): Combination with “a chemotherapeutic agent or therapeutic antibody molecule.”
Claim 9 (or 34): Combination with an “opsonizing antibody molecule.”
Claim 10 / 35: Opsizing antibody examples: anti-CD19, anti-CD20, anti-CD38, anti-Her2/neu, anti-EGFR, anti-CD30, anti-CD33.
Claims 11-19 and 36-44: Narrow those examples to specific molecules including:
- Rituximab (anti-CD20) (Claim 12 / 37)
- Daratumumab (anti-CD38) (Claim 14 / 39)
- Additional explicit options (anti-CD19: not named in the excerpt, but the molecule category is constrained; Her2/neu, EGFR, CD30, CD33 categories are similarly constrained).

Scope critique: these combination limitations read as “use-with” claims, but the dependent claim exemplars can still be used as interpretive anchors for how broadly “opsonizing antibody molecule” is expected to be construed.

Administration and formulation

Routes:
- Subcutaneous: Claim 27 and 51
- Intravenous: Claim 28 and 52
Formulation:
- Pharmaceutical carrier/diluent appears in Claim 26 and 53
The claims do not specify dosing regimen (mg/kg, frequency, cycles). That omission increases practical breadth: any “effective amount” under the method claim can read onto many label-like regimens.

How broad is the tumor coverage (and how credible is it from an enforceability perspective)?

The tumor categories are extensive and essentially cover most common malignancy taxonomies:

Claim 20/45: hematological cancers
Claim 23/48: solid tumors
Claims 21/46 and 24/49: long enumerations of included diseases

Hematologic cancers explicitly listed (representative)

ALL, T-ALL, B-ALL
AML
Non-Hodgkin lymphoma; B-lymphoblastic leukemia/lymphoma
DLBCL
CLL, SLL, CML
Burkitt’s, follicular, marginal zone, CNS lymphoma
Richter’s Syndrome
Multiple myeloma
Myelofibrosis, polycythemia vera
Cutaneous T-cell lymphoma
MGUS
MDS
Immunoblastic large cell lymphoma
Precursor B-lymphoblastic lymphoma and anaplastic large cell lymphoma

Dependent focus (hematologic sub-group):

Claim 22/47: AML, DLBCL, Burkitt’s lymphoma

Solid tumor tissues explicitly listed

Lung, pancreas, breast, liver, ovary, testicle, kidney, bladder, spine, brain, cervix, endometrium, colon/rectum, anus, esophagus, gallbladder, gastrointestinal tract, skin, prostate, pituitary, stomach, uterus, vagina, thyroid.

Dependent cancer examples:

Claim 25/50: pancreatic, ovarian, breast, stomach, colon, prostate, uterine

Enforceability critique: broad tumor lists widen method-use coverage, but they also raise the evidentiary question for the patentee’s written description and enablement across all listed diseases. In litigation, these enumerations often become a pressure point, not because they are automatically invalid, but because a defendant can argue the claims exceed what the specification supports for each disease category.

Patent landscape: where US 10,442,858 fits in the CD47 competitive IP map

Without the rest of the issued patent record (specifically the full spec, prosecution history, and family members), a complete landscape cannot be responsibly asserted. The claim text alone supports one high-confidence landscape conclusion:

This is a “sequence-defined anti-CD47 method” patent

In CD47, the landscape typically bifurcates by:

Target biology strategy (CD47-SIRPα blockade vs other mechanisms)
Antibody design constraints (IgG subclass choice, Fc engineering, RBC hemagglutination mitigation)
Sequence identity (VH/VL and sometimes constant-region sequences)

US 10,442,858 is positioned in the narrow third bucket: sequence-defined antibodies plus functional “non-hemagglutinating” phenotype and SIRPα interaction inhibition.

Design constraint embedded in the claims: hemagglutination

The hemagglutination limitation is a classic CD47 differentiator because many CD47 binders trigger RBC agglutination due to CD47 binding on erythrocytes. By defining a “does not cause significant, or detectable” hemagglutination outcome relative to a reference CD47 mAb that does, the patent attempts to cabin claims to candidates that better manage the RBC risk.

Practical landscape consequence: many anti-CD47 candidates might bind CD47 and inhibit CD47-SIRPα but still fail on a hemagglutination profile. Those candidates can be non-infringing on phenotype only if the claim construction treats the phenotype requirement as a required feature of the method outcome.

Claim-by-claim critical analysis: strengths, vulnerabilities, and likely design-arounds

1) Sequence identity is the main “lock”

Claim 1: VH and VL are locked to SEQ ID NO: 4 and 6.
Claim 29: VH and VL are locked to SEQ ID NO: 24 and 26.

Strength: If a competitor uses a different VH/VL sequence, literal infringement is unlikely for these method claims, even if the competitor’s antibody binds CD47 and does inhibit SIRPα.

Vulnerability for the patentee: sequence-defined claims can be attacked by arguing that the antibody identity is too narrow to cover real-world competitive products, or that the sequences are not meaningfully distinguished in light of the disclosure (depending on the spec and how well those sequences are supported). Still, as a matter of infringement, sequence identity is a strong practical barrier for defendants.

2) IgG4 constant and kappa constant constraints tighten claim set A

Claim set A adds:
- “wild-type human IgG4 heavy chain constant region” (Claim 1)
- kappa constant region (Claim 5)
- specific constant sequences (Claim 6 and Claim 7)

Strength: this can prevent copycat attempts that keep the same VH/VL but change constant regions, at least for this claim set.

Vulnerability for competitors: If a competitor’s therapeutic uses different constant regions (IgG1/IgG2/IgG4 engineered Fc, or different kappa/lambda), it may avoid literal infringement of the IgG4/wild-type and kappa constant sequence-limited claims.

3) SIRPα blockade requirement narrows target mechanism

Claims 2 and 30 require inhibition of CD47-SIRPα interaction.

Strength: This blocks the patentee from having to assert broader mechanism categories such as “immune cell engagement without direct blockade,” depending on interpretation.

Design-around: Use an anti-CD47 antibody that binds but does not inhibit CD47-SIRPα (or does so insufficiently) to attempt to avoid these dependent claim requirements.

4) Hemagglutination is an outcome limitation

Claims 3 and 31: “does not cause significant, or detectable, hemagglutination” relative to a reference mAb.

Strength: This adds a safety-related differentiator and can exclude antibodies that cause RBC agglutination.

Critical legal risk: outcome limitations tied to “reference monoclonal antibody” can become complicated:

What is the reference mAb?
What assay thresholds define “significant” or “detectable”?
Does the claim require the antibody to inherently not cause hemagglutination across all conditions, or under specific assay conditions described in the spec?

This is where disputes tend to focus: assay definition and claim construction.

5) Combination therapy claims likely depend on the same antibody identity

Claims 8-19 and 33-44 do not loosen the antibody identity requirements; they expand “use cases” via combination therapy.

Implication: if a competitor avoids literal antibody sequence match, combination therapy does not help the patentee.

6) Tumor breadth increases method-use coverage, but it also increases litigation surface

Claims 20-25 and 45-50 list large disease sets. That broad list can strengthen commercial value if the antibody works broadly across malignancies that express CD47, but it can be challenged as overreaching if the patent specification does not provide adequate support across each listed disease.

Where infringement risk is likely highest

Risk is highest for products that match, at minimum, the sequence-defined antibody identity and at least some of the functional constraints.

Most dangerous to a competitor

A competitor is most exposed if its anti-CD47 therapeutic:

Uses a VH/VL matching SEQ ID 4/6 or SEQ ID 24/26
Is a human antibody
Uses an IgG4 heavy constant matching the wild-type constant requirement (for claim set A)
Shows SIRPα interaction inhibition
Has a non-hemagglutinating profile in the sense used by the patent

Relatively safer positions (design-around posture)

Different VH/VL sequences, even with CD47 binding and SIRPα blockade
Constant region swaps (for claim set A) or different kappa constant organization
Antibodies that inhibit SIRPα but retain hemagglutination phenotype
Antibodies that bind CD47 without significant CD47-SIRPα inhibition (for those dependent claims)

Key Takeaways

US 10,442,858 is a sequence-defined anti-human CD47 method patent anchored on VH/VL sequences (SEQ ID 4/6 and SEQ ID 24/26) and, for claim set A, explicit wild-type human IgG4 heavy constant region requirements.
The claim set narrows mechanism to CD47-SIRPα interaction inhibition and narrows clinical-risk profile to no significant/detectable hemagglutination relative to a reference CD47 mAb.
Tumor coverage is broad across hematologic and solid cancers with extensive enumerations, but the practical infringement gate is the antibody’s sequence identity and phenotype requirements.
The most credible competitive defense is sequence divergence (VH/VL) and/or constant region divergence (for claim set A), paired with hemagglutination or mechanism differences.

FAQs

Does US 10,442,858 cover all anti-CD47 antibodies?
No. The claims are limited to methods using a monoclonal antibody with specific VH and VL sequences (SEQ ID 4/6 or SEQ ID 24/26) and, in claim set A, a wild-type human IgG4 heavy constant region.
What functional CD47 mechanism does the patent require?
For the dependent claims (2 and 30), the antibody must inhibit the interaction between human CD47 and SIRPα.
Why is hemagglutination central to this patent?
Dependent claims (3 and 31) require that the antibody does not cause significant or detectable hemagglutination versus a reference anti-CD47 antibody that does.
Do the claims require a particular dosing regimen?
The method requires an effective amount. The excerpted claim text does not specify a dosing schedule (frequency or cycle), which keeps the method claims broader.
Can combination regimens avoid infringement?
Combination therapy claims still require the underlying sequence-defined anti-CD47 antibody. If a competitor’s antibody does not meet the sequence and other limitations, combination use alone does not create infringement on these method claims.

References

[1] United States Patent 10,442,858 (claims as provided in the prompt).

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	November 26, 1997	10,442,858	2037-09-21
Janssen Biotech, Inc.	DARZALEX	daratumumab	Injection	761036	November 16, 2015	10,442,858	2037-09-21
Genentech, Inc.	RITUXAN HYCELA	rituximab and hyaluronidase human	Injection	761064	June 22, 2017	10,442,858	2037-09-21
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Patent: 10,442,858

Summary for Patent: 10,442,858