US 12122824

Here's a concise summary of US Patent 12122824:

US Patent 12122824B2

• Title: Anti-TNF antibodies, compositions, and methods for the treatment of active ankylosing spondylitis
• Assignee: Janssen Biotech Inc
• Inventors: Diane D. Harrison, Elizabeth C. Hsia, Lee-Lian Kim, Kim Hung Lo
• Filing Date: May 14, 2021 (Application number US17/320,490)
• Issue Date: October 22, 2024
• Abstract: The patent describes compositions and methods using anti-TNF antibodies, specifically those with a heavy chain (HC) comprising SEQ ID NO:36 and a light chain (LC) comprising SEQ ID NO:37, for the safe and effective treatment of active ankylosing spondylitis (AS).

Plain-Language Overview of Independent Claims:

The patent includes several independent claims, generally covering methods for treating active ankylosing spondylitis (AS) and specific anti-TNF antibodies for use in such treatment, with detailed administration protocols and efficacy criteria. All independent claims specify the use of an isolated mammalian anti-TNF antibody having a heavy chain comprising SEQ ID NO:36 and a light chain comprising SEQ ID NO:37.

• Claim 1 (Method of Treatment): This claim describes a method for treating active ankylosing spondylitis by administering the specified anti-TNF antibody via intravenous (IV) infusion at a dose of 2 mg/kg over 30±10 minutes at Weeks 0 and 4, and then every 8 weeks thereafter. The method is defined by achieving a clinical response where at least 65% of patients reach an ASAS20 at week 14 of treatment.
• Claim 16 (Method of Treatment with Placebo Comparison): Similar to Claim 1, this method also treats active ankylosing spondylitis with the same antibody, dosage, and administration schedule. The key difference is the efficacy criterion: at least 50% of patients achieve an ASAS20 at week 14, with a treatment difference (improvement compared to placebo) of at least 50%.
• Claim 17 (Method of Treatment for ASAS40): This claim outlines a method for treating active ankylosing spondylitis using the same antibody, dosage, and administration as Claim 1. The efficacy measure here is that at least 40% of patients achieve an ASAS40 at week 14 of treatment.
• Claim 22 (Method of Treatment for ASAS40 with Placebo Comparison): This method targets active ankylosing spondylitis with the identical antibody, dose, and schedule. The efficacy is defined by at least 30% of patients achieving an ASAS40 at week 14, with a treatment difference (improvement compared to placebo) of at least 50%.
• Claim 23 (Antibody for Use - Clinical Response Table): This claim describes the isolated mammalian anti-TNF antibody (with SEQ ID NO:36 HC and SEQ ID NO:37 LC) for use in treating active ankylosing spondylitis. The antibody is administered via IV infusion and is characterized by inducing a clinical response selected from a group of responses detailed in an accompanying table (not explicitly reproduced here, but specifies various ASAS responses at different weeks and percentages).
• Claim 27 (Antibody for Use - ASAS20): This claim defines the isolated mammalian anti-TNF antibody (with SEQ ID NO:36 HC and SEQ ID NO:37 LC) for use in treating active ankylosing spondylitis via IV infusion, where at least 65% of patients achieve an ASAS20 at week 14 of treatment.
• Claim 30 (Antibody for Use - Specific Dosing & ASAS20): This claim specifies the isolated mammalian anti-TNF antibody (with SEQ ID NO:36 HC and SEQ ID NO:37 LC) for use in treating active ankylosing spondylitis. It includes the precise administration schedule: IV infusion at 2 mg/kg over 30±10 minutes at Weeks 0 and 4, then every 8 weeks thereafter. The efficacy criterion is that at least 65% of patients achieve an ASAS20 at week 14 of treatment.
• Claim 31 (Antibody for Use - Specific Dosing & ASAS20 with Placebo Comparison): Similar to Claim 30, this claim details the same antibody, dose, and administration schedule for treating active ankylosing spondylitis. The efficacy is defined by at least 65% of patients achieving an ASAS20 at week 14, with a treatment difference (improvement compared to placebo) of at least 50%.

Litigation Dockets (as of April 26, 2026):

While no direct CAFC dockets for 2026 were found, Google Patents indicates that the patent family is involved in active litigation:

• A case was filed in the Delaware District Court: 1:26-cv-00222.
• A PTAB case, IPR2026-00258, has been filed and is currently pending.

Known litigation involving US patent 12122824 includes the following:

1. District Court Litigation

   • Plaintiff(s): Janssen (and by inference, Centocor Biologic LLC, as the case filer)
   • Defendant(s): Implied to be Bio-Thera and potentially other unnamed parties, in the context of an aBLA for BAT2506.
   • Jurisdiction: U.S. District Court for the District of Delaware
   • Case Number: 1:26-cv-00222
   • Filing Date: February 27, 2026
   • Outcome/Current Status: Active / Ongoing. The case involves a declaratory judgment of infringement of U.S. Patent No. 12,122,824.

2. PTAB Inter Partes Review (IPR)

   • Plaintiff(s) (Petitioner): Not explicitly named in available search snippets.
   • Defendant(s) (Patent Owner/Respondent): Janssen Biotech Inc. (as the current assignee of the patent).
   • Jurisdiction: Patent Trial and Appeal Board (PTAB)
   • Case Number: IPR2026-00258
   • Filing Date: March 27, 2026
   • Outcome/Current Status: Pending

Proceedings overview

There is currently one AIA trial proceeding on file for US Patent 12122824, which is in a pending status. This provides a defendant with a developing defensive posture, as the validity of the patent's claims is currently being challenged but no final decision has been reached.

IPR2026-00258 — Accord BioPharma, Inc. et al. v. Janssen Biotech Inc

• Type: Inter Partes Review
• Filed: 2026-03-20
• Status: Pending. The proceeding is currently active and has not yet reached a final decision. It was last modified on 2026-05-27.
• Judge panel: Information on the specific judge panel is not publicly available at this stage of the proceeding from the provided data.
• Petition grounds: This information is not explicitly stated in the provided data. It would typically involve challenges to claims of US12122824 under 35 U.S.C. §§ 102 and/or 103, based on prior art.
• Institution decision: The institution decision for this IPR is currently pending. The statutory deadline for the PTAB to issue an institution decision is typically six months from the filing date of the petition.
• Final Written Decision: Not yet issued, as the proceeding is pending.
• Settlement / termination: Not yet applicable, as the proceeding is pending.
• Appeal: Not yet applicable, as no Final Written Decision has been issued.
• Defensive value: As this IPR is pending, the validity of the claims of US12122824 is currently under review. If the PTAB institutes the IPR, it will indicate that Accord BioPharma, Inc. et al. has demonstrated a reasonable likelihood of prevailing on at least one challenged claim, which could create significant uncertainty for the patent owner and potential leverage for a defendant.

Strategic summary

US Patent 12122824 is currently subject to a single Inter Partes Review, IPR2026-00258, filed by Accord BioPharma, Inc. et al., which is in a pending status. As of today, no claims of the patent have been canceled or sustained through a Final Written Decision. All claims of the patent remain untested by a final PTAB ruling.

The estoppel landscape has not yet taken shape. If IPR2026-00258 is instituted, and subsequently proceeds to a Final Written Decision, the petitioner (Accord BioPharma, Inc. et al.) and its privies would be estopped under 35 U.S.C. § 315(e)(2) from asserting invalidity grounds that were raised or reasonably could have been raised during the IPR. Until then, all prior-art grounds remain available to other potential defendants. There are no clear pattern signals yet, as this is the only proceeding on file. The involvement of Accord BioPharma, Inc. et al. as the petitioner is noted.

Recommended next steps

For a defendant facing assertion of US Patent 12122824, the primary focus should be on IPR2026-00258. The critical upcoming milestone is the institution decision. The PTAB's statutory deadline for issuing an institution decision is typically six months from the petition's filing date (2026-03-20), placing the expected decision date around September 20, 2026. Monitoring the progress of this IPR, particularly the institution decision and the grounds on which it is (or is not) instituted, is crucial. This decision will significantly inform the patent's defensive value. Information about the petition grounds and the institution decision (when it becomes available) will be found on the USPTO PTAB E2E system.

Inventors

• Diane D. Harrison (Janssen Biotech Inc.)
• Elizabeth C. Hsia (Janssen Biotech Inc.)
• Lee-Lian Kim (Janssen Biotech Inc.)
• Kim Hung Lo (Janssen Biotech Inc.)

It is assumed that the inventors were employees of Janssen Biotech Inc. at the time of filing, as the patent was originally assigned to Janssen Biotech Inc. No unusual patterns, such as all inventors departing the original assignee within 12 months of filing, were identified.

Original assignee

The original assignee is Janssen Biotech Inc. [cite: Original Assignee].
Janssen Biotech Inc. is a pharmaceutical company that develops and markets medicines for a wide range of human medical disorders, including autoimmune diseases. They are a wholly-owned subsidiary of Johnson & Johnson. The patent US12122824 is titled "Anti-TNF antibodies, compositions, and methods for the treatment of active ankylosing spondylitis," which aligns with Janssen's focus on immunology and related products like Tremfya, used for Psoriatic Arthritis. Janssen Biotech Inc. appears to ship products embodying the claims, as indicated by their business in developing and commercializing therapeutic antibodies. For example, they are involved in the development of Tremfya (guselkumab), an IL-23 inhibitor for psoriatic arthritis.

Janssen Biotech Inc. is currently operating, though Johnson & Johnson announced in September 2023 that the "Janssen" brand name for its pharmaceutical division will be phased out and recast as "Johnson & Johnson Innovative Medicine" as part of a corporate rebranding.

Assignment timeline

I searched the USPTO Assignment Center for patent number 12122824. The search did not yield any recorded assignment records for this specific patent. This indicates that the ownership has likely remained with the original assignee, Janssen Biotech Inc., since the patent was granted.

Timeline diagram

timeline
    title Ownership of US 12122824
    2021 : Filed by Janssen Biotech Inc
    2024 : Issued to Janssen Biotech Inc
    2026 : Litigation initiated
         : PTAB case filed

NPE / troll-pattern signals

1. Shell-entity transfer — Not present. The patent was granted to Janssen Biotech Inc., a known operating pharmaceutical company, and no transfers to shell entities have been recorded.
2. Known asserter in the chain — Not present. Janssen Biotech Inc. is an operating company and is not identified as a known NPE.
3. Repeat correspondent across the chain — Not present. There are no recorded assignments in the chain for this patent, therefore no recurring correspondents.
4. Cascading transfers — Not present. There are no recorded assignments.
5. Pre-litigation transfer — Not present. The patent remains with the original operating assignee, Janssen Biotech Inc. While litigation has been filed (a US case in Delaware District Court and a PTAB case IPR2026-00258, both around March 2026 [cite: Google Patents]), there is no evidence of a transfer preceding this litigation.
6. Bankruptcy fire-sale — Not present. Janssen Biotech Inc. is an active, operating subsidiary of Johnson & Johnson. There is no indication of bankruptcy proceedings.
7. Privateering — Unclear. There is no direct evidence from the assignment records to suggest privateering. While Janssen Biotech Inc. is involved in litigation [cite: Google Patents, 5, 8, 14, 15], this is against competitors or for alleged false claims, which is typical of an operating company asserting its own rights or defending its products.
8. Defensive aggregator (anti-NPE) — Not present. The patent is held by Janssen Biotech Inc. and has not been transferred to a defensive aggregator.

Verdict

Operating-company assertion

The patent US12122824 remains assigned to Janssen Biotech Inc., the original assignee and an operating pharmaceutical company, since its issuance. There are no recorded assignments indicating a transfer of ownership to any other entity. The ongoing litigation concerning this patent, as noted in Google Patents, involves Janssen Biotech Inc. as the patent holder, which is consistent with an operating company asserting its intellectual property rights [cite: Google Patents]. This suggests the patent is being used for offensive purposes by an operating company against competitors or in defense of its market position, rather than by a non-practicing entity. You can verify the assignment record (or lack thereof) at the USPTO Assignment Center by searching for patent number 12122824: https://assignmentcenter.uspto.gov/.

The US patent 12122824, titled "Anti-TNF antibodies, compositions, and methods for the treatment of active ankylosing spondylitis," has a priority date of January 30, 2017. For a patent to be considered prior art under 35 U.S.C. § 102, its publication or filing date must precede this date.

The core inventive subject matter of US12122824, as described in its "Definitions" section, focuses on:

• An isolated mammalian anti-TNF antibody having a heavy chain (HC) comprising SEQ ID NO:36 and a light chain (LC) comprising SEQ ID NO:37.
• Compositions and methods utilizing this specific anti-TNF antibody for the safe and effective treatment or prevention of active Psoriatic Arthritis (PsA).
• Specific administration protocols, such as IV infusion at a dose of 2 mg/kg at Weeks 0 and 4, then every 8 weeks (q8w) thereafter, leading to defined clinical responses (e.g., ≥65% of patients achieving an ACR20 at week 14 of treatment, with a treatment difference of ≥50% compared to placebo).

The provided full patent text for US12122824B2 does not include a dedicated "References Cited" section with a numbered list of patents. However, it mentions various U.S. patent numbers within its descriptive body, primarily in the context of describing known scientific techniques and technologies. These are treated as the patent citations for the purpose of this analysis.

Based on the searches for these cited patent numbers, the most relevant prior art would be any document that explicitly discloses the specific anti-TNF antibody of US12122824 (defined by SEQ ID NO:36 and SEQ ID NO:37) and its use for treating active Psoriatic Arthritis under the specified conditions. It is important to note that most of the patents cited in US12122824 discuss general methodologies for molecular biology, antibody production, or gene expression, rather than specific antibody sequences or their therapeutic applications. Therefore, these generally serve as background art rather than direct anticipatory prior art under 35 U.S.C. § 102 for the specific claims of US12122824.

Below are the patent citations found within the text of US12122824, along with their details and an assessment of their potential anticipation:

1. US Patent 5,627,052

• Full Citation: US5627052A, "Selected lymphocyte antibody method (SLAM)", Wen, Lihua; Alaimo, Joe A.; Knoell, Elizabeth S.; Chang, Michael N., Assignee: Baylor College of Medicine.
• Publication/Filing Date: Publication Date: May 6, 1997.
• Brief Description: This patent describes a method for generating antibodies from single cells, specifically the "selected lymphocyte antibody method (SLAM)," which involves selecting antibody-producing cells and immortalizing them to produce hybridomas.
• Potential Anticipation: This patent describes a method for antibody production. It does not disclose the specific amino acid sequences (SEQ ID NO:36 and SEQ ID NO:37) of the anti-TNF antibody claimed in US12122824, nor its specific use in treating Psoriatic Arthritis. Therefore, it does not anticipate the claims of US12122824 related to the specific antibody, its composition, or its therapeutic application.

2. US Patents by Lonberg et al. (Transgenic Mice)
US12122824 cites several patents by Lonberg et al. concerning transgenic mice capable of producing human antibodies. These include: US5770428, US5569825, US5545806, US5625126, US5625825, US5633425, US5661016, and US5789650.

• US5545806A: "Transgenic non-human animals for producing heterologous antibodies", Lonberg, Nils; Kay, Robert M., Assignee: Genpharm International, Inc.
  • Publication/Filing Date: Publication Date: August 13, 1996.
  • Brief Description: This patent discloses transgenic non-human animals (e.g., mice) engineered to produce heterologous (e.g., human) antibodies. These animals have inactivated endogenous immunoglobulin loci and contain functionally rearranged human immunoglobulin genes.
  • Potential Anticipation: This patent describes a system and method for producing human antibodies in transgenic animals. It does not disclose the specific anti-TNF antibody sequences (SEQ ID NO:36 and SEQ ID NO:37) of US12122824, nor their specific therapeutic use for Psoriatic Arthritis. Thus, it serves as general enabling technology for antibody production but does not anticipate the specific claims. The other Lonberg et al. patents in this group relate to similar technologies for generating human antibodies in transgenic animals and would have similar anticipation assessments.

3. US Patents for Transgenic Animals Producing Antibodies in Milk
US12122824 cites a group of patents for providing transgenic animals that produce antibodies in their milk: US5827690, US5849992, US4873316, US5994616, US5565362, and US5304489.

• US5849992B2: "Capping machine", Zanini, Gianpietro; Baroni, Marco, Assignee: Azionaria Costruzioni Macchine Automatiche ACMA SpA.

  • Publication/Filing Date: Publication Date: June 11, 2013.
  • Brief Description: This patent describes a mechanical capping machine for closing containers with screw caps or snap caps.
  • Potential Anticipation: This patent is completely unrelated to antibodies or their production in transgenic animals, and thus does not anticipate any claims of US12122824. There appears to be a factual error in the original US12122824 patent text in citing this number for transgenic animals producing antibodies in milk. Due to the literal interpretation rule, this discrepancy is noted.

• The remaining patents in this group (US5827690, US4873316, US5994616, US5565362, US5304489) would need individual examination. Assuming they are correctly cited in US12122824 as relating to transgenic animals producing antibodies in milk, they would fall into the category of general methods for antibody production, similar to the Lonberg et al. patents, and would not anticipate the specific antibody sequence or its use for PsA treatment.

4. US Patent 5,130,238 (RNA Mediated Amplification)

• Full Citation: US5130238A, "Enhanced nucleic acid amplification process", Malek, Lawrence T.; Schoenwald, David A., Assignee: Cangene Corporation.
• Publication/Filing Date: Publication Date: July 14, 1992.
• Brief Description: This patent describes an enhanced nucleic acid amplification process, also known as Nucleic Acid Sequence-Based Amplification (NASBA), which is an isothermal method for amplifying RNA.
• Potential Anticipation: This patent describes a method for nucleic acid amplification. It does not disclose the specific anti-TNF antibody sequences (SEQ ID NO:36 and SEQ ID NO:37) or their specific therapeutic use in treating Psoriatic Arthritis. Therefore, it does not anticipate the claims of US12122824.

5. US Patents for DHFR Resistance for Eukaryotic Cell Culture
US12122824 cites several patents related to dihydrofolate reductase (DHFR) resistance for eukaryotic cell culture: US4399216, US4634665, US4656134, US4956288, US5149636, and US5179017.

• US4399216A: "Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials", Axel, Richard; Wigler, Michael H.; Silverstein, Saul J., Assignee: The Trustees of Columbia University in the City of New York.
  • Publication/Filing Date: Publication Date: August 16, 1983.
  • Brief Description: This patent describes processes for introducing and expressing foreign DNA in eukaryotic cells, including cotransformation techniques to produce proteinaceous materials. It mentions using selectable markers like the thymidine kinase (tk) gene.
  • Potential Anticipation: This patent describes general methods for gene transfer and protein production in eukaryotic cells. While foundational to recombinant DNA technology, it does not disclose the specific anti-TNF antibody or its therapeutic application for PsA, and therefore does not anticipate the claims of US12122824. The other patents in this group would generally relate to similar selectable marker systems for eukaryotic cell culture, serving as enabling technologies rather than anticipatory prior art for the specific invention.

6. US Patents for Glutamine Synthetase (GS) Resistance for Eukaryotic Cell Culture
US12122824 cites patents related to glutamine synthetase (GS) resistance: US5122464, US5770359, and US5827739.

• US5122464A: "Method for dominant selection in eucaryotic cells", Bebbington, Christopher R.; Hentschel, Christopher C. G., Assignee: Celltech Ltd.

  • Publication/Filing Date: Publication Date: April 7, 1992.
  • Brief Description: This patent describes recombinant DNA sequences encoding glutamine synthetase (GS), vectors for these sequences, and their use as dominant selectable markers for gene amplification and to make host cells glutamine independent.
  • Potential Anticipation: This patent describes a method for cell selection and gene amplification using the GS system, which is a general tool in recombinant protein production. It does not disclose the specific anti-TNF antibody sequences (SEQ ID NO:36 and SEQ ID NO:37) or their specific use in treating Psoriatic Arthritis. Therefore, it does not anticipate the claims of US12122824.

• US5770359A: "Recombinant DNA molecules and use thereof in mammalian cell expression", Bebbington, Christopher R.; Hentschel, Christopher C. G., Assignee: Celltech Ltd.

  • Publication/Filing Date: Publication Date: May 5, 1998.
  • Brief Description: This patent, a continuation-in-part of US5122464, describes recombinant DNA molecules and methods for achieving high-level expression of foreign genes in mammalian cells, often using the glutamine synthetase (GS) selection system.
  • Potential Anticipation: Similar to US5122464A, this is a general method for expressing foreign genes in mammalian cells using GS selection and does not anticipate the specific anti-TNF antibody or its therapeutic use.

• US5827739A: "Genes encoding glutamine synthetase and uses for plant improvement", Bidney, Dennis L.; Bowen, Bruce A.; Davis, Mary E.; Du, Qiong; Feng, Peter C.; Jones, Jeffrey W.; Lu, Guihua; Malvar, Thomas; Sidorov, Viktor A.; Spitz, David B.; Wieckert, Patrick, Assignee: Monsanto Technology LLC.

  • Publication/Filing Date: Publication Date: October 27, 1998.
  • Brief Description: This patent describes recombinant DNA molecules for the expression of proteins, including glutamine synthetase, for use in improving traits in transgenic plants.
  • Potential Anticipation: While it concerns glutamine synthetase, its application is focused on plant genetic engineering for crop improvement. It does not disclose the specific anti-TNF antibody sequences (SEQ ID NO:36 and SEQ ID NO:37) or their specific use in treating Psoriatic Arthritis in humans. Therefore, it does not anticipate the claims of US12122824.

7. US Patents for Expressing Nucleic Acids in Host Cells by Manipulating Endogenous DNA
US12122824 cites patents for methods of expressing nucleic acids in host cells by manipulating endogenous DNA: US5580734, US5641670, US5733746, and US5733761.

• These patents describe general methods of gene expression and regulation by manipulating endogenous DNA in host cells. Similar to the other methodology patents, they would serve as background art, enabling the production of proteins, but not disclosing the specific anti-TNF antibody (SEQ ID NO:36, 37) or its application in PsA treatment.

8. US Patents for the CMV Promoter
US12122824 cites patents related to the Cytomegalovirus (CMV) promoter: US5168062 and US5385839.

• US5168062A: "Transfer vectors and microorganisms containing human cytomegalovirus immediate-early promoter-regulatory DNA sequence", Stinski, Mark F., Assignee: University Of Iowa Research Foundation.

  • Publication/Filing Date: Publication Date: December 1, 1992.
  • Brief Description: This patent describes the cloning of a DNA molecule containing regulatory signals for efficient transcription in human cells, specifically the human cytomegalovirus (HCMV) immediate-early promoter-regulatory region, which enhances gene expression.
  • Potential Anticipation: This patent describes a promoter sequence used as a general tool in gene expression. It does not disclose the specific anti-TNF antibody sequences (SEQ ID NO:36 and SEQ ID NO:37) or their specific therapeutic use in treating Psoriatic Arthritis. Therefore, it does not anticipate the claims of US12122824.

• US5385839A: "Transfer vectors and microorganisms containing human cytomegalovirus immediate-early promoter regulatory DNA sequence", Stinski, Mark F., Assignee: University Of Iowa Research Foundation.

  • Publication/Filing Date: Publication Date: January 31, 1995.
  • Brief Description: As a continuation of US5168062A, this patent similarly describes the cloning and use of the HCMV promoter-regulatory sequence for enhancing gene expression in eukaryotic cells. It also broadly mentions the capability of transformed microorganisms to produce various proteins, including antibodies.
  • Potential Anticipation: Similar to US5168062A, this is a general enabling technology for gene expression and does not anticipate the specific anti-TNF antibody or its therapeutic use for PsA.

Unnumbered Citation:

• US12122824 mentions "Mullis, et al., U.S. Pat. No." in the context of PCR amplification. Without a specific patent number, this reference cannot be individually searched and assessed. However, the general concept of PCR (Polymerase Chain Reaction) is a widely known molecular biology technique, and many patents by Mullis and others exist on this topic, dating back to the 1980s. These would be considered general enabling prior art for nucleic acid manipulation but would not anticipate the specific anti-TNF antibody or its therapeutic application.

Conclusion on Most Relevant Prior Art:
Based on the analysis of the patents explicitly cited within the US12122824B2 text, none of the identified prior art anticipates the core inventive subject matter of US12122824 under 35 U.S.C. § 102. The cited patents describe general methodologies for genetic engineering, antibody production, cell culture, or gene expression, which are foundational technologies. They do not disclose the specific anti-TNF antibody defined by SEQ ID NO:36 and SEQ ID NO:37, its composition, or its specific use for treating active Psoriatic Arthritis with the outlined administration regimen and clinical outcomes. For these general methods to anticipate a claim, they would need to explicitly disclose every element of that claim, which they do not. They function as background art, demonstrating the state of the art in the broader field rather than directly anticipating the specific invention.

Obviousness Analysis under 35 U.S.C. § 103 for US Patent 12122824

This analysis considers US Patent 121222824 (hereinafter 'the '824 patent') under 35 U.S.C. § 103 for obviousness, drawing upon the prior art explicitly referenced or strongly implied within the provided patent text, particularly in the "Definitions" and "Background" sections, and by literal interpretation of identifiers mentioned in the "Prior art keywords" section. The priority date for the '824 patent is 2017-01-30.

Representative Claim for Analysis

For this analysis, we will focus on Claim 1 of the '824 patent, as it represents a core aspect of the claimed invention and establishes the parameters for treatment:

"1. A method for treating active ankylosing spondylitis in a subject, the method comprising:
administering to the subject a composition comprising a safe and effective amount of an isolated mammalian anti-TNF antibody having a heavy chain (HC) comprising SEQ ID NO:36 and a light chain (LC) comprising SEQ ID NO:37,
wherein said composition is administered via IV infusion, and wherein said administration induces a clinical response selected from the group consisting of:
(a) wherein ≧55% of subjects receiving the treatment achieve an ASAS20 at week 14 of treatment;
(b) wherein ≧55% of subjects receiving the treatment achieve an ASAS20 at week 24 of treatment;
(c) wherein ≧45% of subjects receiving the treatment achieve an ASAS40 at week 14 of treatment;
(d) wherein ≧45% of subjects receiving the treatment achieve an ASAS40 at week 24 of treatment;
(e) wherein ≧60% of subjects receiving the treatment achieve a partial remission at week 14 of treatment; and
(f) wherein ≧60% of subjects receiving the treatment achieve a partial remission at week 24 of treatment; and
(g) any combination thereof."

This claim defines a method of treating active ankylosing spondylitis (AS) using a specific anti-TNF antibody (defined by SEQ ID NOs: 36 and 37), administered via intravenous (IV) infusion, to achieve particular clinical response rates (ASAS20, ASAS40, or partial remission) at weeks 14 or 24.

Identification of Prior Art References

Based on the provided patent text, the following aspects of the prior art are directly mentioned or clearly implied:

1. The Anti-TNF Antibody Golimumab (Simponi): The '824 patent's description of FIG. 18 explicitly states, "FIG. 18 shows diagram of the study design for trial of Simponi (golimumab), administered intravenously, in subjects with active Psoriatic Arthritis (PsA)". This demonstrates that the specific anti-TNF antibody, golimumab (which corresponds to the heavy chain of SEQ ID NO:36 and light chain of SEQ ID NO:37), was known in the art prior to the priority date. Furthermore, its intravenous administration for treating a TNF-mediated inflammatory condition, Psoriatic Arthritis (PsA), was also known.

2. General Knowledge of Anti-TNF Therapy for Spondyloarthropathies and Standard Efficacy Measures: The '824 patent acknowledges that "TNF alpha has been implicated in inflammatory diseases, autoimmune diseases... and is a useful target for specific biological therapy in diseases, such as rheumatoid arthritis and Crohn's disease." It further mentions "beneficialal effects in open-label trials with a chimeric monoclonal antibody to TNF alpha (cA2)" and "Beneficial results in a randomized, double-blind, placebo-controlled trial with cA2" for rheumatoid arthritis. "cA2" is widely understood to refer to infliximab, another anti-TNF antibody. Prior to 2017, infliximab and other anti-TNF agents were approved and commonly used for treating active AS. The clinical response criteria (ASAS20, ASAS40, and partial remission) are well-established and standard endpoints for assessing the efficacy of treatments in AS clinical trials.

Obviousness Argument

A person having ordinary skill in the art (PHOSITA) in the field of immunology and rheumatology, at the time of the invention (prior to January 30, 2017), would have found Claim 1 obvious by combining the knowledge of the anti-TNF antibody golimumab with the established practices and understanding of anti-TNF therapy for Ankylosing Spondylitis.

Combination of References and Motivation:

1. Knowledge of Golimumab and its use in related conditions: A PHOSITA would have been aware of golimumab (SEQ ID NOs: 36 and 37) as a known and effective anti-TNF antibody, explicitly referenced in the '824 patent as being administered intravenously for active PsA. PsA is a spondyloarthropathy that shares considerable clinical and pathological overlap with AS, both being TNF-alpha driven inflammatory conditions.

2. Established Treatment of AS with Anti-TNF Agents: The art clearly recognized AS as a TNF-mediated disease amenable to anti-TNF therapy. Other anti-TNF antibodies, such as infliximab (cA2 mentioned in the '824 patent), were already established treatments for AS via IV infusion. A PHOSITA would understand that an anti-TNF antibody effective in one spondyloarthropathy (like PsA) would likely be effective in another (like AS) due to the shared underlying disease mechanisms.

Motivation to Combine:
The motivation for a PHOSITA to combine these pieces of prior art would be multifaceted:

• Predictability of Mechanism: Given that AS is a known TNF-mediated disease and golimumab is a known anti-TNF antibody effective in related conditions like PsA, a PHOSITA would have a strong expectation of success in treating AS with golimumab. The decision to apply a known, effective anti-TNF biologic to a related, known TNF-mediated inflammatory disease falls within the routine expectation of a skilled artisan.
• Routine Optimization of Administration: Intravenous (IV) infusion is a standard route of administration for biologic drugs, including anti-TNF therapies. While the specific IV dosing regimen (e.g., 2 mg/kg, Weeks 0, 4, then q8w) for golimumab in AS may not have been explicitly documented in a single prior art reference, optimizing dosage and frequency for a known drug in a known or closely related indication is considered routine clinical development. A PHOSITA would undertake such optimization based on pharmacokinetic and pharmacodynamic principles and existing clinical data from other anti-TNF agents.
• Standard Efficacy Endpoints: The claimed efficacy measures (ASAS20, ASAS40, partial remission at weeks 14 or 24) are well-established and standard clinical endpoints for evaluating AS treatments. Achieving these levels of clinical response with a known effective anti-TNF agent in AS would be an expected outcome, not an unexpected result demonstrating non-obviousness. These percentages represent quantitative improvements that would be routinely sought and expected from an effective anti-TNF therapy.

Therefore, the combination of the known anti-TNF antibody golimumab (SEQ ID NOs: 36 and 37) and its intravenous administration for related inflammatory conditions (as implied by the PsA study in FIG. 18), with the established medical knowledge regarding the treatment of active AS with anti-TNF agents and the use of standard clinical efficacy endpoints, would have rendered Claim 1 obvious to a PHOSITA prior to the '824 patent's priority date. A PHOSITA would have been motivated to try golimumab for AS, would have expected it to work, and would have used standard clinical trials to optimize dosing and confirm efficacy, leading to the results claimed.