Patent: 10,675,358

Summary for Patent: 10,675,358

Title:	Antibody adjuvant conjugates
Abstract:	The invention provides an immunoconjugate comprising an antibody construct which includes an antigen binding domain and an Fc domain, an adjuvant moiety, and a linker, wherein each adjuvant moiety is covalently bonded to the antibody via the linker. Methods for treating cancer with the immunoconjugates of the invention are also described.
Inventor(s):	Alonso; Michael Nathaniel (Santa Clara, CA), Engleman; Edgar George (Atherton, CA), Ackerman; Shelley Erin (Mountain View, CA), Kenkel; Justin (Mountain View, CA), Lee; Arthur (San Jose, CA), Jackson; David Y. (Belmont, CA)
Assignee:	The Board of Trustees of the Leland Stanford Junior University (Stanford, CA) Bolt Biotherapeutics, Inc. (Redwood City, CA)
Application Number:	16/140,309
Patent Claims:	see list of patent claims

Executive summary: U.S. Patent 10,675,358 claims a class of antibody-drug or antibody-adjuvant type immunoconjugates defined by a specific “Formula IVb” adjuvant linker moiety (Adj) attached at a defined attachment point to an antibody (Ab) that includes an antigen-binding domain and an Fc domain. The claim set is broad as to antibody identity (expressly listing multiple blockbuster IgG antibodies and “a biosimilar thereof”) and broad as to antigen targets (large receptor/ligand panel including HER2 and PD-L1). The patent’s real boundaries are the Adjugant structure constraints (Adj in Formula IVb with specified heteroatoms, substituent constraints on R4 including butyl exemplars, and integer parameters a and r) plus conjugate architecture (Ab includes Fc; with optional modified Fc including insertion/deletion/substitution and deglycosylation/afucosylation). In freedom-to-operate terms, the tightest infringement risk generally sits with conjugates that use the same (or substantially the same) Formula IVb Adj moiety and attachment geometry. If competitors use different adjuvant chemistry, different attachment positions, different R4 classes, or different conjugation paradigms, the claims narrow sharply even if the antibody and target are the same.

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What are the key claim elements in US 10,675,358 and what do they practically cover?

Core independent claim 1 anchor: An immunoconjugate “according to Formula IVb” where:

• Ab (antibody): has (i) antigen-binding domain and (ii) Fc domain.
• Adj (adjuvant moiety): has a defined chemical formula (Adj as “of formula” in the patent’s Formula IVb; characterized in the claims by substituent constraints including:
  • R4 is an alkyl/heteroalkyl/cycloalkyl/heterocycloalkyl/aryl/heteroaryl/arylalkyl/heteroarylalkyl group with 1–8 carbons
  • each J = hydrogen
  • each U = N
  • t = 2
  • Q is not present
  • dashed line indicates the attachment point to G1, and G1 is a bond
• Integer parameters:
  • a = 1 to 40
  • r = 1 to 10
• Optionality is introduced by dependent claims, especially modified Fc and specific numeric ranges.

Claim 24 is a second anchor: Same structure concept but restricted to trastuzumab as Ab and Adj with R4 specifically = butyl and r constrained to 1–4.

Which structural variables create the infringement boundaries?

1. Adj structural constraints (highest sensitivity)

   • Competitors can often “design around” by changing the adjuvant chemistry away from the specific Formula IVb constraints (U being N, J being hydrogen, Q absent, t fixed, attachment via G1 bond).
   • Even if the competitor’s molecule is also an “immunoconjugate,” claim 1 requires matching the Formula IVb Adj.

2. R4 range and the butyl exemplar

   • Claim 1 allows R4 among broad 1–8 carbon options across multiple chemical classes.
   • Claim 9 narrows to R4 = butyl, and claim 24 sets R4 = butyl with r = 1–4. This creates two infringement “rails”:
     • the general rail (claim 1) where R4 can be any qualifying 1–8 carbon substituent class;
     • the specific rail (claim 9/24) covering butyl.

3. a and r integer ranges

   • Claim 1 gives a up to 40 and r up to 10.
   • Claim 10 constrains r to 1–4, and claim 24 already fixes r to 1–4.
   • If competitor r values lie outside these integers (for example r > 10), they fall outside the literal claim set as written.

4. Attachment architecture

   • The claims specify dashed attachment line to G1 which is a bond. Practical infringement in most litigations will turn on whether the competitor’s conjugation yields the same connection point/chemotype consistent with Formula IVb’s attachment.

Which antibody-related choices broaden the estate?

Claim 1 is antibody-agnostic in architecture terms, but dependent claims 16–21 explicitly list antibody exemplars and include “a biosimilar thereof.” Claim 18–21 further single out:

• trastuzumab (claim 18 and 19/21).

The antigen-binding domain target list in claim 11 is wide and includes, among others:

• HER2 (claim 12 and 13)
• PD-L1 (claim 14 and 15)
• and many other oncology immune checkpoints and adhesion/ECM and growth factor targets (CDH1, CD19, CD20, EpCAM, MUC1/16, EGFR, VEGF, PD-1/PD-L2, LAG-3, etc.).

This breadth matters for enforceability because it reduces the chance that a competitor can avoid infringement simply by swapping targets while using the same Ab class and the same Adj chemistry.

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How strong is the patent estate for US 10,675,358: is it chemistry-limited or antibody-limited?

Strength profile: The estate is Adj-limited first, and antibody/target-limited second.

• The claims define a particular Adj moiety under Formula IVb with explicit variable constraints.
• In contrast, the antibody identity is permissive (either by functional definition in claim 1 or by list in dependent claims).
• Target selection is framed as binding to selected antigens, but infringement still depends on meeting the immunoconjugate structural definition.

Where the estate looks strongest

• Conjugates using the same Adj chemistry (Formula IVb with matching parameterization) attached to antibodies containing Fc domains.
• Products that use trastuzumab or antibodies enumerated in claim 16/17, especially if they also use butyl (R4 = butyl) and r values within 1–4 (claim 24 family).

Where the estate looks weaker (design-around leverage)

• Competitors can avoid these claims by using:
  • different adjuvant moieties not captured by Formula IVb,
  • different attachment linkers or connection geometry inconsistent with the “G1 bond” representation,
  • R4 groups outside the 1–8 carbon class or with different heteroatom patterns that do not meet “J hydrogen / U N / Q absent / t = 2” restrictions.
• Modified Fc language is optional, not required in claim 1, but it can increase specificity if the prior art contains general Fc modifications but not this Adj.

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What patents and prior art typically overlap with Formula IVb immunoconjugates?

Only the claim text was provided. Without the full publication record (specification, priority data, file history, and claims as originally filed), an accurate “what patents are in the closest prior art set” mapping cannot be produced.

What can be said from the claim language alone:

• The estate sits at the intersection of:
  1. antibody conjugation to defined small-molecule adjuvant chemotypes,
  2. Fc engineering (insertion/deletion/substitution; deglycosylation; afucosylation),
  3. broad selection of oncology targets.

In enforcement practice, the most relevant prior art is usually from:

• immunostimulatory payload/linker chemistries used as vaccine/adjuvant analogs,
• ADC-like conjugation chemistry adapted to immune-modulatory small molecules,
• Fc-effector enhancement platforms (afucosylation/deglycosylation and engineered Fc),
• antibody-target combinations (HER2 and PD-L1 are especially crowded).

However, the specific “Formula IVb” adjuvant identity must be compared against known small-molecule adjuvants used in conjugates. That comparison requires the actual structural depiction from the patent specification and the identity of the adjuvant moiety, which is not recoverable from the user-supplied claim excerpt alone.

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How does claim scope differ between claims 1 and 24 (trastuzumab + R4=butyl + r=1–4)?

Claim 1 scope:

• Ab: any antibody with antigen-binding domain + Fc domain
• Adj: Formula IVb with R4 in many permitted classes (1–8 carbons), a up to 40, r up to 10
• Target: wide through dependent binding selections
• Fc: modified Fc only via dependent claims 2–4; otherwise unmodified Fc still satisfies claim 1.

Claim 24 scope:

• Ab: explicitly trastuzumab
• Adj: Formula IVb with R4 = butyl
• r = 1 to 4
• a: 1–20 via dependent claims 27–28
• Fc modifications only via dependent claims 25–26

Practical infringement implication

• If a competitor uses trastuzumab conjugated to butyl Adj with r 1–4, claim 24 becomes a primary risk hook even if their Ab is not in the general list or their Fc is unmodified.
• If a competitor uses non-trastuzumab antibodies, claim 1 is the hook only if their Adj matches Formula IVb with permissible R4 and parameterization.
• If a competitor matches the adjuvant chemistry but uses a different Ab class that still fits “antigen binding domain + Fc domain,” claim 1 remains viable.

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What formulations and biologics are covered: is this an ADC, an immunostimulatory conjugate, or a vaccine-adjuvant conjugate?

The claim language uses “immunoconjugate” with an “adjuvant moiety” (Adj). It does not define a cytotoxic payload explicitly in the excerpt; the payload is characterized as an adjuvant chemical entity via Formula IVb.

Covered compositions:

• Claim 22: composition comprising a plurality of immunoconjugates according to claim 1.
• Claim 23: composition includes excipients.

Covered antibody types:

• Claim 16/17: includes multiple monoclonals and their biosimilars.
• Claim 20/21: specifically biosimilar-of-trastuzumab.

This language is consistent with a platform that can be used with existing IgG antibodies across targets, which is a major breadth lever for licensing and cross-product enforcement.

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What does the Orange Book status question mean for this patent?

This patent is a U.S. utility patent (10,675,358). The excerpt does not provide:

• the drug product names tied to the patent,
• any FDA reference listed drug (RLD),
• any Orange Book listing entries.

Without those linkages, a correct Orange Book status analysis cannot be produced from the provided information.

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When does US 10,675,358 lose exclusivity, and how do related exclusivity periods affect generic entry?

A loss-of-exclusivity timeline depends on:

• the patent’s expiration date (filing date, priority, and any PTA),
• any FDA regulatory exclusivity attached to the relevant RLD/biologic,
• whether this is listed in the Orange Book or BLA-related exclusivity context.

No patent term data, expiration date, or FDA filing link is provided in the user input, so a timeline cannot be generated accurately.

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What Paragraph IV or biosimilar challenges could target this patent?

The claim set is directed to conjugate compositions. If any biosimilar or generic applicant sought approval of an antibody component plus conjugate formulation, the legal strategy would typically involve:

• non-infringement by using a different Adj moiety (Formula IVb non-match),
• invalidity by prior art showing the same conjugate structure or by obviousness combinations,
• or inequitable conduct depending on prosecution facts.

But the excerpt provides no information about:

• which approved product (if any) corresponds to the immunoconjugate,
• which company is launching,
• whether the patent is listed in the regulatory reference product’s patent listing ecosystem.

Therefore, no specific “which companies are challenging” or “what litigation affects” analysis can be made reliably.

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What patent litigation risk exists: how would an infringement case be structured?

Based on the claim text alone, infringement arguments would likely focus on claim construction of:

1. Formula IVb / Adj structure
   • Whether the accused adjuvant moiety matches the variable definitions (R4 class and carbon count; J hydrogen; U N; Q absent; t = 2; attachment via dashed line to G1 bond).
2. Integer ranges a and r
   • Whether the accused conjugate has the same parameter values, which can be a measurement/production-parameter issue.
3. Antibody architecture
   • Whether Ab includes an antigen binding domain and an Fc domain.
4. Fc modifications
   • Only necessary for claims 2–4 and 25–26; claim 1/24 do not require modified Fc.
5. Composition claims
   • Composition claims 22–23 and 29–30 are likely co-extensive with the underlying immunoconjugate claims.

Design-around would target the Adj structure first, then the conjugation position/chemistry, then parameter ranges.

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How does US 10,675,358 compare with other immunoconjugate/Fc-engineered platform patents?

Without additional patents or the full specification, a comparative patent strength ranking cannot be computed.

However, from the claim excerpt’s structure:

• this patent is best characterized as a conjugate-specific structural claim (Adj Formula IVb) deployed across broad antibody/target selections,
• with optional Fc engineering hooks that can matter in obviousness analysis (if prior art teaches Fc modification) and in infringement (if accused products also use engineered Fc).

That combination tends to make the estate less vulnerable to “generic antibody swap” tactics, because the key variable is the adjuvant moiety structure, not the antibody identity.

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Does the claim language cover biosimilars and what is the commercial impact?

Claim 16/17 include “a biosimilar thereof” for multiple antibodies, and claim 20/21 explicitly cover biosimilars of trastuzumab.

Commercial impact:

• It reduces the ability of a challenger to argue that they avoid infringement by using a biosimilar antibody instead of the reference product.
• For licensing and settlements, it broadens the patent’s reach across branded-to-biosimilar supply chains.

In practice, the most material commercial exposure is where competitors can source biosimilar IgG at lower cost but still deploy the same immunoconjugate Adj chemistry. If the Adj chemistry is the proprietary element, the patent’s commercial leverage is concentrated in the conjugation system and payload technology.

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Key Takeaways

• The estate is structurally anchored to “Adj” defined by Formula IVb. Antibody identity and antigen target are broad; the adjuvant chemistry constraints create the main infringement boundaries.
• Claim 1 covers a wide swath of immunoconjugates where Ab has Fc and the Adj meets the specified Formula IVb variable constraints (R4, J, U, t, Q absence, a and r ranges).
• Claim 24 is a tighter, trastuzumab-specific lane requiring R4 = butyl and r = 1–4, making it a high-value hook for trastuzumab-based conjugates with that exact adjuvant parameterization.
• Fc engineering is optional via dependent claims (modified Fc; deglycosylated/afucosylated), so unmodified Fc products may still fall within claim 1 if Adj matches.
• Composition claims track the immunoconjugate claims. If the immunoconjugate is not infringed, the composition claims generally do not salvage infringement.
• Biosimilars are expressly within scope via “biosimilar thereof” language, strengthening licensing leverage across antibody sourcing strategies.

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FAQs

1. What part of US 10,675,358 most likely determines infringement: the antibody, the antigen target, or the adjuvant moiety?
   The adjuvant moiety defined by Formula IVb and its variable constraints most directly determines infringement.

2. If a product uses HER2-targeting trastuzumab, does that alone trigger US 10,675,358?
   No. HER2 binding and trastuzumab help satisfy dependent targeting/Ab elements, but infringement still requires the immunoconjugate to match the Formula IVb Adj constraints.

3. How do R4 and r integer ranges affect design-around strategies?
   Competitors can target R4 outside allowed classes/carbon counts or adjust r beyond the claimed ranges (notably claim 24’s r 1–4).

4. Do modified Fc requirements apply to the broadest claim?
   No. Modified Fc is introduced via dependent claims; the broad independent claim only requires Ab with an Fc domain.

5. Do the composition claims create independent protection beyond the immunoconjugate claims?
   No. They require immunoconjugates meeting claim 1 or claim 24, then add plurality/excipients.

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References (APA)

No external sources were cited because the prompt did not include the patent publication record, priority data, file history, prosecution dates, or any FDA/Orange Book listing information.

Details for Patent 10,675,358

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	November 26, 1997		2038-09-24
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	September 25, 1998		2038-09-24
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	February 10, 2017		2038-09-24
Immunex Corporation	ENBREL	etanercept	For Injection	103795	November 02, 1998		2038-09-24