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Patent 10,040,848 claims analysis and US patent landscape for chimeric/humanized anti-histone H3 (and H2B) antibody conjugates

Executive summary: US 10,040,848 claims a broad antibody-based conjugate platform anchored to fixed anti-histone H3 (claim 1) or anti-histone H2B (claim 15) CDR sets, with downstream dependent claims that expand coverage across antibody formats (F(ab’)2, Fab’, Fab, Fv, scFv), conjugate payload classes (radionuclides, toxins, cytokines and other immunomodulators, and a long list of small-molecule drugs), and composition forms (fusion proteins; therapeutic compositions). The strongest claim focus is the CDR-anchored antigen-binding domain coupled to “at least one therapeutic or diagnostic agent.” The weakest portion, as a freedom-to-operate risk driver, is the very broad payload enumeration coupled to a single antibody CDR definition, which typically invites invalidity challenges for lack of enablement and overbreadth, and narrows enforceability to the antibody species defined by the CDRs plus realistic conjugation teachings.

What is US Patent 10,040,848 actually claiming for anti-histone H3 antibodies?

Direct answer: Claim 1 covers a chimeric or humanized anti-histone H3 antibody (or antigen-binding fragment) whose heavy- and light-chain CDR sequences are fixed, where the antibody (or fragment) is conjugated to at least one therapeutic or diagnostic agent.

Claim 1 core coverage elements

Molecule identity is anchored to six CDR sequences
- Heavy chain CDRs (anti-H3):
  - CDR1: SYWMH (SEQ ID NO:100)
  - CDR2: NIDPSDSETHYNQKFKD (SEQ ID NO:101)
  - CDR3: EKITDDYNYFDY (SEQ ID NO:102)
- Light chain CDRs (anti-H3):
  - CDR1: RASESVDSYGNSFMH (SEQ ID NO:103)
  - CDR2: HASNLES (SEQ ID NO:104)
  - CDR3: QQNNEDPLT (SEQ ID NO:105)
Antibody format is not restricted in claim 1
- It states “antibody or antigen-binding fragment thereof” and then later constrains formats in dependent claims.
Payload requirement
- “Conjugated to at least one therapeutic or diagnostic agent.”
- This is the enforceability pivot: infringing products need the CDR-defined antibody and a conjugation to one of the recited or encompassed agent types.

What the CDR definition does to claim scope

It is restrictive on the binding domain (good for enforceability).
It is permissive on the payload (broad for enforceability risk and for validity attacks).
Because the CDR sequences are fully enumerated, the infringement case is mostly an IP-spec match on the antibody’s variable regions plus evidence of conjugation.

Which dependent claims expand the US 10,040,848 anti-histone H3 coverage across payload classes?

Direct answer: The patent expands claim 1 across (i) therapeutic agent classes (claim 2-7), (ii) toxin sub-classes (claim 4), (iii) immunomodulator and cytokine sub-classes (claim 5-6, 19-20), (iv) radionuclide lists (claim 7, 21), and (v) diagnostic agent classes including radionuclides and imaging labels (claim 9-12, 23-26).

Payload matrix for anti-H3 (claims 2-12)

Dependent claim	Payload category	Scope mechanism	Representative sub-items
Claim 2	Therapeutic agent classes	“Selected from” enumerated categories	second antibody, radionuclide, immunomodulator, anti-angiogenic, pro-apoptotic, cytokine, chemokine, drug, toxin, hormone, siRNA, enzyme
Claim 3	Therapeutic drug list	“Drug is selected from” long catalog	5-fluorouracil; doxorubicin; paclitaxel; dasatinib; erlotinib; imatinib; sunitinib; ibrutinib; etc.
Claim 4	Toxin class	toxin selected from enumerated list	ricin, abrin, saporin, diphtheria toxin, Pseudomonas exotoxin, etc.
Claim 5	Immunomodulator class	immunomodulator selected from enumerated list	cytokine plus many other immunomodulator classes
Claim 6	Cytokine list (broad)	cytokine selected from enumerated list	IL family (IL-1 through IL-25), TNF-α/β, IFN-α/β/γ/λ, VEGF, TGF-α/β, G-CSF/GM-CSF, EPO, etc.
Claim 7	Radionuclides	radionuclide selected from enumerated list	^111In, ^177Lu, ^90Y, ^64Cu, ^68Ga, ^131I, ^89Zr, many others
Claim 8	Antibody fragment format	fragment format selected from list	F(ab’)2, Fab’, Fab, Fv, scFv
Claim 9	Diagnostic agent classes	diagnostic agent selected from list	radionuclide, radiological contrast, paramagnetic ion, metal, fluorescent/chemiluminescent labels, ultrasound contrast, photoactive
Claim 10	Diagnostic radionuclides	radionuclide selected from enumerated imaging list	^18F, ^64Cu, ^68Ga, ^99mTc, ^131I, ^86Y, etc.
Claim 11	Paramagnetic ions	enumerated	Cr(III), Mn(II), Fe(III/II), Co(II), Ni(II), Cu(II), Gd(III), etc.
Claim 12	Fluorescent labels	enumerated dyes/labels	Alexa series, BODIPY, fluorescein derivatives, rhodamines, Texas Red, etc.

Anti-H3 therapeutic “drug conjugates” are covered extremely broadly

Claim 2-3 effectively covers antibody-drug conjugates (ADCs) and antibody-drug conjugate-like constructs because the payload includes a long list of cytotoxic and targeted oncology drugs. The patent does not limit linker technology, drug loading, or site of conjugation in the claim text you provided. That breadth is a classic claim-amplifier for enforcement, but a classic validity stress point.

How does US 10,040,848 differ for anti-histone H2B antibodies (claims 15-28)?

Direct answer: The patent adds a parallel CDR-defined anti-histone H2B antibody (claim 15), using another set of fixed heavy/light CDR sequences, and then mirrors the same conjugated-payload logic through claims 16-20 and radionuclide/diagnostic formatting claims 21-26, plus fusion and therapeutic compositions (claims 27-28).

Claim 15 core CDR sets for anti-H2B

Heavy chain CDRs (anti-H2B):
- CDR1: SYVMY (SEQ ID NO:110)
- CDR2: YINPYNDGTKYNEKFKG (SEQ ID NO:111)
- CDR3: PGDGYPFDY (SEQ ID NO:112)
Light chain CDRs (anti-H2B):
- CDR1: RSSQSIVHSNGNTYLE (SEQ ID NO:113)
- CDR2: KVSNRFS (SEQ ID NO:114)
- CDR3: FQGSHVPYT (SEQ ID NO:115)

Payload and composition structure for H2B mirrors H3

Therapeutic payload classes: claim 16
Toxin list: claim 18
Immunomodulator/cytokine: claims 19-20
Radionuclide list: claim 21
Fragment formats: claim 22
Diagnostic payload classes: claims 23-26
Fusion protein: claim 27
Therapeutic composition: claim 28

Business consequence: any competitor designing around this patent must clear either the H3 CDRs or the H2B CDRs, and must also avoid conjugating the defined antibody species to the payload categories that are claimed.

What formats are protected, and how much does that matter for infringement risk?

Direct answer: The patent explicitly covers multiple antibody fragment formats (claim 8 for H3; claim 22 for H2B) and generic “antigen-binding fragments” broadly (claim 1 and claim 15).

Protected fragment formats

F(ab’)2
Fab’
Fab
Fv
scFv

If a competitor uses an alternative engineered binding format not listed in the dependent claims, infringement may still be argued under “antigen-binding fragment thereof” in the independent claim, but the dependent claim language typically strengthens the patent holder’s position on literal infringement for common fragment formats.

What therapeutic payloads are most likely to drive claim construction and litigation posture?

Direct answer: The claim’s operational breadth is dominated by (i) radionuclides (claims 7 and 21), (ii) toxins (claims 4 and 18), and (iii) cytokines/immunomodulators (claims 5-6 and 19-20). The “drug” list in claims 3 and 17 is extensive and can support many ADC or drug-conjugate theories, but its breadth is also where invalidity arguments often concentrate.

Radionuclide coverage is unusually wide

The radionuclide lists include therapeutic beta emitters, alpha emitters, and many diagnostic positron emitters and imaging radioisotopes. That typically supports:

broad infringement theories for radioimmunoconjugates (theranostics)
fewer “design-around” options via isotope selection alone

Cytokine/immunomodulator breadth is extensive

Claims enumerate ILs, interferons, TNF, growth factors, chemokine-like categories, and many others. This can capture:

immunocytokine constructs
radio- or toxin-linked “immune modulation” conjugates

What fusion protein and composition coverage exists beyond the conjugate constructs?

Direct answer: The patent includes:

Fusion proteins comprising the claim 1 anti-H3 or claim 15 anti-H2B antibody (claims 13 and 27)
Therapeutic compositions containing the claim 1 or claim 15 antibody (claims 14 and 28)

Litigation significance

“Therapeutic composition” claims can be used to target commercial formulations even if a product’s “active” is packaged with excipients.
“Fusion protein” claims can capture designs where the antibody is fused to other protein domains beyond classic small-molecule/toxin/radio payload conjugation, depending on how the spec defines “fusion.”

How strong is the patent estate for enforcement based on claim structure alone?

Direct answer: Strength is highest on the binding specificity side (CDR sequences are fixed) and lowest on payload breadth and conjugation enablement issues, which are likely to be litigated if competitors practice close to the CDR-defined antibodies with different conjugates.

Strength drivers

Fully specified CDR sequences
- Limits antibody variability in infringement.
Clear “conjugated to at least one therapeutic or diagnostic agent”
- Supports product-category capture across ADC, immunotoxin, radioimmunotherapy, and imaging conjugates.

Vulnerability drivers

Overbreadth risk from enormous payload enumeration
- A single antibody skeleton is paired with a very wide payload universe, including large therapeutic catalogs.
Enablement risk when antibody conjugates cover many payload modalities
- Different payloads can require different conjugation chemistries and manufacturing conditions.
Potential indefiniteness if conjugation is not operationally defined
- Without claim-limiting language on linker chemistry or conjugation site, defendants may argue claim scope is not sufficiently supported by the disclosure.

These are claim-construction and validity pressure points that typically surface in post-grant review or district court litigation.

What “design-around” levers exist, based strictly on the claims provided?

Direct answer: Competitors can aim to avoid infringement primarily by:

Using antibodies with different CDR sequences
Avoiding conjugation to the claimed therapeutic/diagnostic agent categories
Avoiding the covered fragment formats if relevant, though “antigen-binding fragment” language can still reach other fragments

Most direct lever: change CDR sequences

Because CDR sequences are enumerated, changing CDR1/2/3 on either heavy or light chain is the cleanest conceptual workaround. However, competitors must still bind histone H3/H2B effectively, which is a biology constraint.

Second lever: keep binding, change conjugation purpose

If a product binds histones but does not include a conjugated therapeutic/diagnostic agent, it may sit outside claim 1/15 as written. But most commercial constructs in this space are conjugated, so this lever is often narrow.

How does US 10,040,848 compare across anti-histone targets (H3 vs H2B) for coverage breadth?

Direct answer: The patent treats anti-histone H3 and anti-histone H2B as parallel protected targets, each with fixed CDR sequences and mirrored payload categories. A competitor that changes the antigen target from H3 to H2B would still risk infringing depending on whether the product uses the exact CDR-defined H2B antibody species.

Practical risk framing

If a competitor’s platform is “anti-histone” but antigen selection is variable, they face a dual hazard: the patent covers both H3 and H2B CDR-defined antibodies.
Enforcement likely turns on whether the binding domains match either CDR set.

What regulatory and litigation relevance follows from these claims?

Direct answer: The claims are not tied to a specific FDA application type in your excerpt. However, the payload categories strongly indicate potential product classes that would be evaluated under:

oncology biologics pathways (if therapeutic)
radiopharmaceutical/diagnostic imaging pathways (if diagnostic radionuclides/labels)

Paragraph IV biosimilar or generic angle

Because the claims are for antibodies/conjugates, generic substitution is generally not available. The most relevant competitive challenge would be:

infringement litigation against “similar” conjugate products
post-grant validity challenges (IPR/PGR) against the claim breadth

Your provided record contains no jurisdictional litigation history, Orange Book status, or FDA reference product linkages.

Key takeaways

US 10,040,848 is structured as a CDR-defined anti-histone antibody conjugate patent with two antigen targets: histone H3 (claim 1) and histone H2B (claim 15).
The strongest enforceability hook is the fixed heavy/light CDR sequences; infringement analysis should focus on variable-region identity.
The broadest claim risk for competitors is the payload universe: radionuclides, toxins, cytokines/immunomodulators, and an extensive list of drugs plus diagnostic imaging labels.
“Fusion protein” and “therapeutic composition” dependent claims can extend enforcement to packaged commercial offerings.
The claims are likely to invite validity attacks focused on overbreadth/enablement because the same antibody definition is paired with very large payload catalogs across modalities.

FAQs

Do US 10,040,848 claim 1 or claim 15 require a specific linker chemistry for the conjugated agent?
The provided claim text requires conjugation to at least one therapeutic/diagnostic agent but does not specify linker type in the claims excerpt.
If a competitor uses a different anti-histone antibody but it binds histone H3, can they still infringe?
Literal infringement depends on matching the claimed CDR sequences; binding alone is not enough in the provided claim language.
Are both therapeutic and diagnostic uses covered under US 10,040,848?
Yes. Claim 1/15 cover conjugates “to at least one therapeutic or diagnostic agent,” with dependent claims enumerating both.
Does the patent cover scFv and Fab formats for both histone H3 and H2B antibodies?
Yes. Claim 8 covers H3 fragments and claim 22 covers H2B fragments, both including scFv, Fab, Fab’, Fv, and F(ab’)2.
What radionuclides are covered for diagnostic imaging under the H3 and H2B claim sets?
The diagnostic radionuclide lists appear in claims 10 (H3) and 24 (H2B) and include common imaging isotopes such as ^18F, ^64Cu, ^68Ga, ^99mTc, and ^131I, among others.

References

No external sources were cited because no patent bibliographic metadata, prosecution history, claim set numbering provenance beyond the text provided, litigation records, or FDA/Orange Book links were included in the input.

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	January 10, 1978	⤷ Start Trial	2038-02-02
Takeda Pharmaceuticals U.s.a., Inc.	NATPARA	parathyroid hormone	For Injection	125511	January 23, 2015	⤷ Start Trial	2038-02-02
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Patent: 10,040,848

Summary for Patent: 10,040,848