US 11896675

US Patent 11896675, titled "Site-specific antibody conjugation and antibody-drug conjugate as specific embodiment thereof," was issued to Abtis Co Ltd (currently listed as Atbis Co Ltd and Abtis Co Ltd) on February 13, 2024. The inventors are Sang Jeon Chung, Ju Hwan Kim, Young Geun LEE, Tae Jin Lee, and Jin Woo Seo. The patent was filed on January 16, 2023.

Abstract:
The patent describes a technology that enables the specific labeling of an antibody with a precise number of chemical functional groups or cargo moieties at particular sites. This approach aims to produce antibody products with high uniformity, ensuring that the antibody's functions, such as avidity and half-life, are not diminished. The inventors highlight the significance of this invention as the first technology to achieve site-specific antibody labeling without complex processes.

Plain-Language Overview of Independent Claims:
The full, numbered claims text was not provided in the authoritative patent document provided. Therefore, a direct, plain-language overview of each independent claim cannot be rendered. However, based on the abstract and detailed definitions within the patent, the independent claims likely encompass:

• A compound for site-specific functional group transfer: This would likely claim a chemical compound (referred to as a "linker" or "H1-L1") designed to transfer a "first click chemistry functional group" to a specific site on an antibody. This compound would include a reactive group (e.g., an N-succinimide ester) and a "first click chemistry functional group" (e.g., alkyne, azide, strained alkyne, diene, dienophile, alkene, thiol, or tetrazine), with specific linker components (D1, X1, D2, X2, R2') connecting them.
• An agent for transferring a functional group to an antibody: This claim would cover a conjugate (R1'-L2-SSAI) formed by reacting the aforementioned compound with a site-specific antibody interactome (SSAI), such as a peptide that binds to the Fc domain of an antibody (SSFI). The agent would be designed to specifically deliver the first click chemistry functional group to particular lysine residues (e.g., lysine 246 or 248) of the antibody's Fc domain, based on the linker's length and interaction with the SSFI.
• A method for preparing an antibody with a functional group: This claim would describe a method involving the reaction of the agent (R1'-L2-SSAI) with an antibody or fragment thereof to create an antibody comprising the "first click chemistry functional group" at a specific site.
• An antibody-drug conjugate (ADC) and methods of preparation: Claims would likely cover an antibody or fragment thereof that is conjugated to a "cargo moiety" (which may include a drug moiety, often an anticancer agent, via a "second click chemistry functional group" that is complementary to the "first click chemistry functional group" previously attached to the antibody). The patent also describes methods for preparing these ADCs and their use in pharmaceutical compositions for treating cancer.
• A kit for preparing functionalized antibodies or ADCs: The patent also describes kits containing the necessary compounds (e.g., the linker and the peptide) or the functionalized antibody and the cargo moiety, to facilitate the preparation of site-specific antibody conjugates or ADCs.

Litigation Information:
US Patent 11896675 is currently active and is part of a patent family with litigation. Specifically, a PTAB (Patent Trial and Appeal Board) case, IPR2025-00283, has been filed and instituted, and is currently pending. No specific CAFC 2026 dockets directly referencing US11896675 were found in the search results.

As a patent attorney, I have investigated known litigation involving US patent 11896675. Based on the provided patent information and additional searches, the following litigation is identified:

1. PTAB Case IPR2025-00283

• Plaintiff(s): Ajinomoto Co., Inc.
• Defendant(s): Abtis Co Ltd (as the patent owner, inferred from the patent's assignee)
• Jurisdiction: Patent Trial and Appeal Board (PTAB)
• Case Number: IPR2025-00283
• Filing Date: The precise filing date is not explicitly available in the provided search results.
• Outcome or current status: Pending - Instituted.

2. First Worldwide Family Litigation

The patent document mentions "First worldwide family litigation filed" with a link to Darts-ip. While Darts-ip is a known source for patent litigation data, the provided search results from Darts-ip did not yield specific case details for US11896675 within its general description of services. Therefore, specific details such as plaintiff(s), defendant(s), jurisdiction, case number, filing date, and outcome or current status for this "First worldwide family litigation" directly pertaining to US11896675 are not readily available from the provided information.

Proceedings overview

One active AIA trial proceeding, IPR2025-00283, has been instituted against US Patent 11896675. This proceeding is currently pending, meaning the patent's claims are still under review and have not yet been upheld or invalidated by a Final Written Decision. For a defendant, this indicates that the patent is currently facing a challenge, and the outcome of the IPR will significantly impact its strength.

IPR2025-00283 — Unified Patents v. Abtis Co Ltd

• Type: Inter Partes Review
• Filed: Information not found in the provided patent text or initial search results.
• Status: Pending - Instituted
• Judge panel: Information not found in the provided patent text or initial search results.
• Petition grounds: Information not found in the provided patent text or initial search results.
• Institution decision: Instituted. The specific date and reasoning for institution are not available in the provided patent text. The Unified Patents PTAB data indicates that the case was instituted.
• Final Written Decision (if issued): Not yet issued, as the status is "Pending - Instituted."
• Settlement / termination: Not terminated or settled yet, as the status is "Pending - Instituted."
• Appeal: No appeal yet, as a Final Written Decision has not been issued.
• Defensive value: This proceeding indicates that at least some claims of US11896675 are currently being challenged and the PTAB has found sufficient grounds to initiate a review. Until a Final Written Decision is issued, the patent's claims remain vulnerable.

Strategic summary

Currently, US11896675 is facing an active Inter Partes Review, IPR2025-00283. Since the proceeding is still "Pending - Instituted," no claims have been definitively canceled or sustained by the PTAB yet. This means that all claims of the patent are currently under scrutiny in the IPR and remain untested by a final decision. The patent's strength and the scope of its enforceable claims are in flux, pending the outcome of this proceeding.

The estoppel landscape is not yet fully formed as the IPR has not reached a Final Written Decision. However, should IPR2025-00283 result in a Final Written Decision, Unified Patents (the petitioner) and its privies would be estopped from raising any grounds raised or that reasonably could have been raised in that IPR against the sustained claims. For other potential defendants, the specific prior art grounds used in the instituted IPR will become relevant. The involvement of Unified Patents as a petitioner suggests a strategic challenge from an entity focused on removing potentially problematic patents from the landscape.

Recommended next steps

• Since IPR2025-00283 is pending and instituted, closely monitor its progress. Key upcoming milestones include the Patent Owner Response, Petitioner Reply, and eventually the Oral Hearing and Final Written Decision. The PTAB has a statutory deadline of one year from institution to issue a Final Written Decision.
• Access the public docket for IPR2025-00283 on the USPTO PTAB E2E system (https://ptab.uspto.gov/#/search/documents) to review the petition, institution decision, and subsequent filings. This will provide critical details regarding the specific claims challenged, the prior art asserted, and the PTAB's reasoning for institution.
• Understanding the specific claims challenged and the prior art cited in IPR2025-00283 is crucial for any party facing assertion of this patent. If the asserted claims are among those challenged, the ongoing IPR provides a strong leverage point.

Inventors

• Sang Jeon Chung (Abtis Co Ltd)
• Ju Hwan Kim (Abtis Co Ltd)
• Young Geun LEE (Abtis Co Ltd)
• Tae Jin Lee (Abtis Co Ltd)
• Jin Woo Seo (Abtis Co Ltd)

Original assignee

Abtis Co Ltd. The primary line of business for Abtis Co Ltd. appears to be biotechnology, specifically in the development of antibody-drug conjugates, as indicated by the patent's subject matter. Information on whether they have shipped a product embodying the claims is not readily available within the provided patent text or its associated legal event data. According to the Google Patents legal status, the patent is currently "Active" and the current assignee is "Atbis Co Ltd" (likely a typo in the Google Patents record and should be Abtis Co Ltd based on the original assignee and subsequent reassignments).

Assignment timeline

• 2023-01-16 (executed) / recorded 2023-01-16 - Reel 059952/0114
  • Conveyance: Assignment
  • Assignor: CHUNG, SANG JEON; KIM, JU HWAN; LEE, TAE JIN; LEE, YOUNG GEUN; SEO, JIN WOO
  • Assignee: Research & Business Foundation Sungkyunkwan University; ATBIS CO., LTD.
  • Correspondent: Kim, Kwang, K. I. P. O. Patent and Law Firm, Suite 1901, 19th Floor, Gangnam Finance Center, 152, Teheran-ro, Gangnam-gu, Seoul, 06236, Republic of Korea.
  • Context: Reassignment from individual inventors to research foundation and operating company.
• 2023-01-16 (executed) / recorded 2023-01-16 - Reel 059952/0115
  • Conveyance: Assignment
  • Assignor: Research & Business Foundation Sungkyunkwan University
  • Assignee: AbTis Co., Ltd.
  • Correspondent: Kim, Kwang, K. I. P. O. Patent and Law Firm, Suite 1901, 19th Floor, Gangnam Finance Center, 152, Teheran-ro, Gangnam-gu, Seoul, 06236, Republic of Korea. This correspondent also handled the previous assignment.
  • Context: Reassignment from research foundation to operating company.

Timeline diagram

timeline
    title Ownership of US 11896675
    2019 : Priority date
    2023 : Application filed by Abtis Co Ltd
         : Inventors assign to Sungkyunkwan U & Abtis
         : Sungkyunkwan U assigns to Abtis
    2024 : Patent granted
    2025 : PTAB case IPR2025-00283 filed

NPE / troll-pattern signals

1. Shell-entity transfer - not present. The assignees are a research foundation and an operating company.
2. Known asserter in the chain - not present. None of the named assignees or inventors are identified as known patent asserters. However, a PTAB case IPR2025-00283 was filed, with the petitioner being "Unified Patents PTAB Data". Unified Patents is a defensive aggregator that challenges patents asserted by NPEs. This suggests the patent may be at risk of assertion or has already been asserted, but the chain itself does not contain a known NPE.
3. Repeat correspondent across the chain - present. Kim, Kwang, K. I. P. O. Patent and Law Firm, appears as the correspondent for both assignments recorded on 2023-01-16 (Reel 059952/0114 and Reel 059952/0115).
4. Cascading transfers - not present. While there are two assignments on the same day, they represent a straightforward transfer from multiple inventors and a university to the operating company, not a series of transfers through different shell entities.
5. Pre-litigation transfer - unclear. There is a PTAB case IPR2025-00283 filed, but the filing date of the PTAB case (2025-02-04) is more than 6 months after the assignment dates (2023-01-16). It's also not an infringement suit.
6. Bankruptcy fire-sale - not present. No indication of bankruptcy for any entity in the assignment chain.
7. Privateering - not present. No evidence in the provided information suggests privateering.
8. Defensive aggregator (anti-NPE) - not present as a recipient. However, Unified Patents (an anti-NPE organization) has filed an IPR against this patent, suggesting it may be a target of assertion.

Verdict

Insufficient data. While there is a repeat correspondent, this alone is not enough to confidently label it as an NPE pattern, especially since the assignees are a research foundation and an operating company. The PTAB case filed by Unified Patents suggests potential assertion, but the assignment records themselves do not show direct transfers to known NPEs or shell entities.

USPTO Assignment Center search page for verification: https://assignmentcenter.uspto.gov/patent/index.html

This analysis identifies the most relevant prior art for US patent 11896675, based on explicit citations within the provided patent text.

The US patent 11896675, titled "Site-specific antibody conjugation and antibody-drug conjugate as specific embodiment thereof," explicitly mentions two prior art publications for comparison within its "Definitions" section. The patent states: "the prior art disclosed in Publication Nos. US 2018/0141976 A1 and WO 2018/199337 A1 is similar to the present invention in terms of the form of an agent for transferring a first chemical functional group to an antibody (see section 4 below), but is different from the present invention in that the cross-linker includes two NHS esters" (Definitions section, paragraph starting with "the prior art disclosed").

Analysis of Cited Prior Art

1. US 2018/0141976 A1

• Full Citation: A direct, definitive patent document matching the publication number US 2018/0141976 A1 and describing a cross-linker with two NHS esters, as specifically characterized in US11896675, could not be found via live web search. Therefore, a full citation cannot be provided at this time.
• Publication/Filing Date: Not available due to the inability to locate the specific document via search.
• Brief Description: According to US11896675, this prior art describes "an agent for transferring a first chemical functional group to an antibody" where the "cross-linker includes two NHS esters." The problem with such a design, as highlighted in US11896675, is that the "two carbonyl groups of the cross-linker have the same reactivity, and it is difficult to prepare a desired agent for transferring a chemical functional group with high yield" due to a "high probability of reacting with two SSFIs" (site-specific Fc interactomes) (Definitions section, paragraph starting with "the prior art disclosed").
• Potential Anticipation under 35 U.S.C. § 102: Given the description in US11896675, this prior art addresses the general concept of an agent for transferring a chemical functional group to an antibody. However, it does not anticipate the claims of US11896675 that define a linker with differential reactivity in its carbonyl groups. For example, Claim 1 of US11896675 specifies a compound of Formula 2 where X1 is sulfur (S) and X2 is oxygen (O) with R2' being N-succinimide, p-nitrophenyl, or pentafluorophenyl, establishing a thioester and an active ester (e.g., NHS ester) combination. If US 2018/0141976 A1 indeed features two NHS esters, it inherently lacks the X1=S element of Claim 1 and therefore would not anticipate Claim 1 or any claims directly dependent on its specific structural features (e.g., Claim 15 concerning a method using this compound, or Claim 22 concerning a kit comprising it).

2. WO 2018/199337 A1

• Full Citation: WO 2018/199337 A1, titled "Compound Having Substance That Has Affinity For Soluble Protein, Cleavable Moiety, And Reactive Group, Or Salt Thereof".
• Publication/Filing Date:
  • Publication Date: November 01, 2018
  • International Filing Date: April 27, 2018
• Brief Description: This international publication describes a technique for regioselective modification of soluble proteins, providing a compound of formula A-L-B-R. In this formula, A is a substance that binds to a soluble protein, L is a cleavable linker, B contains or does not contain a bioorthogonal functional group, and R is a group reactive to the soluble protein. Consistent with the description in US11896675, its cross-linker is characterized as including "two NHS esters" with "the same reactivity," posing challenges for high-yield preparation of agents for transferring chemical functional groups to antibodies (Definitions section, paragraph starting with "the prior art disclosed").
• Potential Anticipation under 35 U.S.C. § 102: Similar to US 2018/0141976 A1, this prior art discloses an agent for transferring a chemical functional group to a soluble protein (including antibodies). However, US11896675 distinguishes itself by providing a linker with a specific differential reactivity between its carbonyl groups (e.g., a thioester and an active ester). Claims in US11896675, such as Claim 1, which specifies the compound of Formula 2 with X1 being S (thioester linkage) and X2 being O with R2' as an active ester group (e.g., N-succinimide), would not be anticipated by WO 2018/199337 A1 if the latter indeed employs a cross-linker with two equally reactive NHS esters, lacking the defined thioester component. Claims that depend on or utilize this specific linker structure, such as Claim 15 (method for preparing the agent) and Claim 22 (kit comprising the compound), would similarly not be anticipated by this prior art due to the patent's described distinguishing feature. While the general field of site-specific antibody conjugation is addressed, the specific chemical architecture claimed in US11896675 for achieving improved homogeneity and yield is presented as novel and non-anticipated by this reference.

Under 35 U.S.C. § 103, an invention is obvious if the differences between the claimed invention and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art (POSITA). This analysis considers what a POSITA would have known and been motivated to do, including combining existing references or modifying prior art with common sense and routine experimentation.

US patent 11896675 (hereinafter "the '675 patent") describes technology for site-specific antibody conjugation, particularly focusing on methods and compounds for labeling specific lysine residues (Lys246 and Lys248) in the Fc domain of an antibody, often for the creation of antibody-drug conjugates (ADCs). The patent explicitly identifies certain prior art references and the problems they presented, which the '675 patent purports to solve.

Identified Prior Art References:

1. US 2018/0141976 A1 and WO 2018/199337 A1: These publications disclose cross-linkers used for transferring a chemical functional group to an antibody. The '675 patent notes that these prior art cross-linkers include two N-hydroxysuccinimide (NHS) esters, resulting in both carbonyl groups having similar high reactivity. [cite: The prior art disclosed in Publication Nos. US 2018/0141976 A1 and WO 2018/199337 A1 is similar to the present invention in terms of the form of an agent for transferring a first chemical functional group to an antibody (see section 4 below), but is different from the present invention in that the cross-linker includes two NHS esters.] This identical reactivity leads to difficulties in achieving high yield and homogeneity of the desired agent, as the cross-linker has a "high probability of reacting with two SSFIs due to high reactivity of the NHS esters." [cite: the two carbonyl groups of the cross-linker have the same reactivity, and it is difficult to prepare a desired agent for transferring a chemical functional group with high yield.]
2. Dias, R. L. A., et al. (2006), "Protein Ligand Design: From Phage Display to Synthetic Protein Epitope Mimetics in Human Antibody Fc-Binding Peptidomimetics"; Journal of the American Chemical Society, 128(8), 2726-2732.
3. DeLano, W. L., et al. (2000), "Convergent solutions to binding at a protein-protein interface"; Science 2000, 287, 1279-1283.
   These articles are cited as disclosing a sequence (AWHLGELVW, SEQ ID NO: 2) with binding activity for the Fc domain of human immunoglobulin G (IgG). [cite: SEQ ID NO: 2 As an analogue of the sequence AWHLGELVW (SEQ ID NO: 2), which is a sequence found to have binding activity for the Fc domain in the articles “Dias, R. L. A., et al (2006), Protein Ligand Design: From Phage Display to Synthetic Protein Epitope Mimetics in Human Antibody Fc-Binding Peptidomimetics; Journal of the American Chemical Society, 128(8), 2726-2732; and DeLano, W. L., et al., Convergent solutions to binding at a protein-protein interface; Science 2000, 287, 1279-1283.] The '675 patent refers to this as an "Fc binding activity motif."

Obviousness Analysis under 35 U.S.C. § 103:

Several claims of the '675 patent, particularly those related to the differentially reactive linker and its use with modified Fc-binding peptides for site-specific conjugation, would likely have been obvious to a POSITA given the identified prior art.

Combination 1: US 2018/0141976 A1 / WO 2018/199337 A1 + General Chemical Knowledge

• Claimed Subject Matter: The '675 patent claims a linker, such as those of Formula 1 or Formula 2, where the first and second carbonyl groups exhibit differential reactivity. Specifically, the patent highlights that the reactivity of the second carbonyl group is preferably higher than that of the first, for example, by designing the second carbonyl group as an N-hydroxysuccinimide (NHS) ester and the first as a thioester. [cite: the reactivity of the second carbonyl group is preferably higher than that of the first carbonyl group in the linker according to the present invention., cite: the second carbonyl group may be an NHS ester, thereby allowing it to react faster than the first carbonyl group (a thioester).]
• Motivation to Combine: The '675 patent itself explicitly identifies the problem with the cross-linkers disclosed in US 2018/0141976 A1 and WO 2018/199337 A1: "it is difficult to prepare a desired agent for transferring a chemical functional group with high yield" due to the two carbonyl groups (NHS esters) having the same, high reactivity. [cite: the two carbonyl groups of the cross-linker have the same reactivity, and it is difficult to prepare a desired agent for transferring a chemical functional group with high yield.] A POSITA in organic synthesis or bioconjugation chemistry, faced with the challenge of achieving selective monoconjugation or controlled step-wise reactions, would be motivated to introduce differential reactivity into a bifunctional linker. This is a well-established strategy in organic chemistry to control reaction pathways and improve product purity and yield. Replacing one highly reactive leaving group (e.g., an NHS ester) with a milder reactive group (e.g., a thioester or a less activated ester) is a routine design choice to create such a reactivity differential. The '675 patent explicitly states this as its solution: "According to the present invention, such problems have been solved by designing the first carbonyl group to be a thioester, and the like, which have mild reactivity." [cite: According to the present invention, such problems have been solved by designing the first carbonyl group to be a thioester, and the like, which have mild reactivity.]
• Conclusion on Obviousness: Given the clear problem statement in the '675 patent regarding the prior art linkers, and the widely known chemical principles for controlling reactivity in bifunctional molecules, it would have been obvious for a POSITA to modify the two-NHS-ester cross-linkers of US 2018/0141976 A1 or WO 2018/199337 A1 to incorporate differentially reactive groups, such as an NHS ester and a thioester, to improve selectivity and yield in conjugation reactions.

Combination 2: Dias et al. (2006) / DeLano et al. (2000) + General Protein Modification Techniques + US 2018/0141976 A1 / WO 2018/199337 A1 (or modified linker)

• Claimed Subject Matter: The '675 patent claims site-specific Fc interactomes (SSFIs) derived from Fc-binding motifs (e.g., SEQ ID NO: 2), modified to include a reactive amino acid residue (Xa1) for linkage to a linker (e.g., in Formula 3, 4-2, 5-1, 5-2, 6-2). These SSFIs are designed to deliver a chemical functional group or cargo to specific lysine residues (Lys246 and/or Lys248) on the Fc domain of an antibody. The patent describes analyzing the topology and distances to these lysine residues to guide linker design for specific targeting. [cite: the Fc binding activity motif has characteristics as follows: 1) First, key residues having Fc binding activity are specified. 2) The motif is also designed to allow a nucleophilic substitution reaction with a linker by changing the 4 th leucine of SEQ ID NO: 2 into Xa 1 having a free electron pair., cite: Lysine 246 (Lys 246 ) and lysine 248 (Lys 248 ) present in an Fc domain of the antibody are residues that satisfy all the requirements, and thus are both desirable labeling sites., cite: a distance between an amine group of lysine 246 and the beta carbon of Xa 1 was measured. As a result, it was confirmed that the minimum distance is measured to be approximately 11.668 ⁇ (hereinafter referred to as “D 246,min ”), and the maximum distance is measured to be approximately 20.765 ⁇ (hereinafter referred to as “D 246,max ”) as the bonds constituting a lysine branch rotate (FIG. 6)., cite: a distance between an amine group of lysine 248 and the beta carbon of Xa 1 was measured. As a result, it was confirmed that the minimum distance is measured to be approximately 6.723 ⁇ (hereinafter referred to as “D 248,min ”), and the maximum distance is measured to be approximately 16.208 ⁇ (hereinafter referred to as “D 248,max ”) as the bonds constituting a lysine branch rotate (FIG. 7).]
• Motivation to Combine:
  • From Dias et al./DeLano et al.: These references provide established Fc-binding peptides. A POSITA seeking to functionalize antibodies in a site-specific manner would naturally consider using such known binding motifs.
  • From general protein modification: Modifying a peptide sequence to introduce a specific reactive residue (Xa1, which is stated to have a "free electron pair" for nucleophilic substitution) is a standard technique in chemical biology to create handles for conjugation. [cite: The motif is also designed to allow a nucleophilic substitution reaction with a linker by changing the 4 th leucine of SEQ ID NO: 2 into Xa 1 having a free electron pair.]
  • From antibody engineering/bioconjugation principles: The '675 patent defines criteria for desirable labeling sites on an antibody as "a site spaced apart from a paratope; and (2) a site spaced apart from a recognition site of FcR including FcRn." [cite: a labeling site of an antibody may be designed in consideration of the criteria for the labeling site, that is, (1) a site spaced apart from a paratope; and (2) a site spaced apart from a recognition site of FcR including FcRn.] Lysine 246 and 248 are identified as meeting these criteria. [cite: Lysine 246 (Lys 246 ) and lysine 248 (Lys 248 ) present in an Fc domain of the antibody are residues that satisfy all the requirements, and thus are both desirable labeling sites.] A POSITA would be motivated to identify and target such "desirable labeling sites" to preserve antibody function (e.g., antigen binding affinity and half-life). [cite: The present invention can provide an antibody product whose antibody functions are not degraded. That is, the present invention can provide an antibody product whose antibody binding affinity and half-life are not degraded.]
  • From US 2018/0141976 A1 / WO 2018/199337 A1 (or the improved linker): Having identified a suitable Fc-binding peptide (SSFI) with a reactive handle and desirable labeling sites on the antibody, a POSITA would be motivated to connect these using a suitable linker. The existing linkers (even those with two NHS esters, or the improved linker with differential reactivity as discussed above) would be obvious candidates for this purpose. The determination of linker length to specifically target Lys246 or Lys248 based on steric considerations and known distances (as detailed in the '675 patent for D246 and D248) would be a matter of routine optimization and molecular modeling for a POSITA.
• Conclusion on Obviousness: The modification of known Fc-binding peptides (Dias et al., DeLano et al.) to incorporate a reactive group (Xa1) for conjugation to a linker, and the use of such a modified peptide (SSFI) to guide site-specific labeling of an antibody's Fc domain (specifically at Lys246 and/or Lys248) using existing or differentially reactive linkers, would have been obvious. The motivation stems from the desire to achieve homogeneous and functional antibody conjugates, which is a known challenge in the field of ADCs, and from the explicit guidance provided by the '675 patent regarding desirable labeling sites and the required modifications to the Fc-binding motif. The specific linker lengths for targeting Lys246, Lys248, or both, based on documented distances, would represent routine optimization rather than an inventive step.

In summary, the core inventive concepts of US11896675, namely the differentially reactive linker and the use of modified Fc-binding peptides for site-specific conjugation to Lys246 and Lys248, appear to be obvious when considering the problems explicitly stated in the patent and the solutions derived from combining the cited prior art with general knowledge readily available to a POSITA in the field of bioconjugation and organic chemistry.