Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the application
This application is a 371 of PCT/KR2023/001077, filed on 01/20/2023 and has a US filing date of 07/19/2024 and claims priority to KOREA, REPUBLIC OF 10-2022-0008310, filed 01/20/2022 and KOREA, REPUBLIC OF 10-2023-0008353, filed 01/19/2023. Accordingly, priority is based on the filing date of 01/20/2022.
Claims 19-21 are pending with claims 1-18 having been canceled in the paper presented on 07/19/2024.
The IDS statement filed on 07/19/2024 is in compliance with 37 CFR 1.97 and 1.98 and has been considered.
Detailed examination
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 19 is rejected under 35 U.S.C. § 101 as being directed to a judicial exception without reciting additional elements sufficient to integrate the exception into a practical application or to amount to significantly more than the exception itself.
As described in MPEP § 2106, subsection III, Step 2A of the Office’s eligibility analysis is the first part of the Alice/Mayo test, i.e., the Supreme Court’s "framework for distinguishing patents that claim laws of nature, natural phenomena, and abstract ideas from those that claim patent-eligible applications of those concepts." Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 217-18, 110 USPQ2d 1976, 1981 (2014) (citing Mayo, 566 U.S. at 77-78, 101 USPQ2d at 1967-68). Like the other steps in the eligibility analysis, evaluation of this step should be made after determining what the inventor has invented by reviewing the entire application disclosure and construing the claims in accordance with their broadest reasonable interpretation.
Step 2A asks: Is the claim directed to a law of nature, a natural phenomenon (product of nature) or an abstract idea? In the context of the flowchart in MPEP § 2106, subsection III, Step 2A determines whether:
Step 2A, Prong One analysis: Claim 19 recites detecting a copy number variation or an allele of an HLA gene in a biological sample; predicting a high risk of onset of a cancer immunotherapy-induced immune-related adverse event (irAE) when specified HLA CNVs or alleles are detected; and when a high risk is predicted, treating the irAE in the subject by administering a corticosteroid or immune-suppressant. The core of the claim is the recognition of an association between the presence of certain HLA variants and the likelihood of irAE onset. That association is a natural correlation/law of nature. Under the Alice/Mayo framework and MPEP § 2106, claims that recite a natural relationship and apply it with generic, conventional steps are directed to a judicial exception.
Step 2A, Prong Two: The additional elements of claim 19 do not, on this record, integrate the judicial exception into a practical application. The claim recites detecting the HLA variant in a biological sample and administering a corticosteroid or immunosuppressant when the risk is predicted.
The treatment step of administering a corticosteroid or immunosuppressant is treated as well-understood, routine, and conventional (WURC) in light of the present specification and that know to the person of ordinary skill in this art. The specification states that most early-stage or low-grade irAEs can be managed with corticosteroids or immunosuppressants. The specification also describes conventional detection methodologies, including sequencing, exome sequencing, next generation sequencing (NGS), pyrosequencing, microarray hybridization, allele-specific PCR, dynamic allele-specific hybridization, PCR extension analysis, PCR-SSCP, and Taqman technique.
Accordingly, the claim recites conventional data collection and conventional treatment activity applied after recognition of the natural correlation. Those steps, considered individually and as an ordered combination, do not amount to an inventive application of the correlation.
Step 2B: The claim does not recite any additional element, or ordered combination of additional elements, that amounts to significantly more than the natural correlation itself. The recited detecting and treating steps are, on this record, routine implementation steps. The claim does not recite a specific unconventional technological improvement to detection, diagnosis, or treatment. Nor does it recite a nonconventional treatment protocol that changes the character of the claim from a claim to a natural correlation into a patent-eligible practical application.
Accordingly, claim 19 is directed to a natural correlation between specified HLA variants and irAE risk, and the additional steps do not provide sufficient inventive concept or practical application. Therefore, claim 19 is rejected under 35 U.S.C. § 101.
35 USC 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 20 and 21 are rejected under 35 U.S.C. § 112(b) as failing to particularly point out and distinctly claim the subject matter regarded as the invention.
Claims 20 and 21 each recite dependency on claim 1, however, claims 1-8 have been canceled by amendment. Because the dependent claims refer to a nonexistent claim, the dependency chain is broken and creates an internal claim-reference defect and leaves the scope of claims 20 and 21 unclear on the face of the claim set. Therefore, claims 20 and 21 are rejected under 35 U.S.C. § 112(b).
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim 19 is rejected under 35 U.S.C. § 103 as being unpatentable over Ahn et al. in view of Jordanova et al. and further in view of Shukla et al., Castro et al., US 20200069782, Matsukane et al., and Chen et al.
Ahn et al. teaches that HLA polymorphisms are associated with disease susceptibility and resistance across multiple disease states, and that HLA typing may be used to predict disease susceptibility, resistance, and related outcomes. Ahn et al. therefore establishes the general principle that HLA variation can serve as a biomarker for disease-risk assessment.
Jordanova et al. discloses that mutations in HLA class II genes, including deletions and stop-codon-forming mutations, can result in loss of HLA-DR and HLA-DQ expression in diffuse large B-cell lymphoma. The reference further discusses hemizygous deletion, mitotic recombination, and mutation of the remaining allele as mechanisms of HLA loss.
Shukla et al. teaches a computational pipeline for HLA typing from exome sequencing data and detection of somatic HLA mutations in cancer. Shukla et al. further teaches that somatic HLA mutations are associated with immune evasion and are enriched in tumors with immune infiltration.
Castro et al. teaches that somatic B2M and HLA mutations are associated with higher tumor mutation burden, higher fractions of HLA-binding neoantigens, and increased immune infiltration and cytotoxicity. Castro et al. therefore reinforces the relevance of HLA alterations in cancer immune recognition.
US 20200069782 A1 teaches a neoantigen-selection workflow in which HLA alleles are used to predict peptide-HLA binding. The reference expressly uses HLA-B*35:01 in predicted neoantigen tables, demonstrating that allele-level HLA characterization and use of specific HLA-B alleles in cancer-related predictive workflows was known.
Matsukane et al. (Sci. Rep. 2021; 11:1324) teaches the clinical importance of predicting immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors and states that specific HLA genes have been reported as risk factors for irAEs. Matsukane further teaches that corticosteroids or immunosuppressants are used to manage many irAEs.
Chen et al. (PNAS 2020; 117(38):23684-23694) teaches biomarker-based stratification in immune checkpoint blockade therapy and supports the broader clinical utility of identifying predictive biomarkers in the immunotherapy setting.
Claim 19 recites detecting a copy number variation or allele of an HLA gene in a biological sample, predicting a high risk of onset of a cancer immunotherapy-induced irAE when specified HLA variants are detected, and treating the irAE by administering a corticosteroid or immunosuppressant. On the present record, the art teaches that HLA locus alterations are biologically meaningful in disease and cancer, that HLA biomarkers were known and useful in predictive cancer workflows, that HLA genes were relevant to irAE risk in immune checkpoint inhibitor-treated patients, and that corticosteroids/immunosuppressants were conventional irAE treatments. Accordingly, the recited method is an application of known HLA biomarker principles to a known immunotherapy safety problem.
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the cited teachings of Ahn et al., Jordanova et al., Shukla et al., Castro et al., US 20200069782 A1, Matsukane et al., and Chen et al. to arrive at the method of claim 19, because the art taught that HLA variation and HLA structural alteration were well known cancer-associated biomarkers, that HLA allele detection by sequencing and allele-specific predictive workflows were established, that HLA genes were relevant to irAE risk in immune checkpoint inhibitor-treated patients, and that irAEs were conventionally managed with corticosteroids or immunosuppressants. While the specific HLA CVN are not disclosed the art was cognizant that variation in copy number and mutation of these markers are indicative or the risk of irAE as is disclosed by the prior art.
No claim is allowed.
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GARY BENZION, Ph.D.
Supervisory Patent Examiner
Art Unit 1681
/GARY BENZION/Supervisory Patent Examiner, Art Unit 1681
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