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 .
Election/Restrictions
Applicant’s election of the particular species of: TET2-CHIP mutation; and the particular SNP that is rs2296311, in the reply filed on 08/22/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
In light of the Examiner’s search of the elected polymorphism (i.e.: rs2296311), the particular SNPs that are rs2887399 andrs11846938 (recited in claims 18 and 24) are rejoined with the elected polymorphism.
Claims 32 and 34-38 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention (i.e.: directed to ASXL-CHIP mutations), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 0/22/2025.
Claim Objections
Applicant is advised that should claim15 be found allowable, claim 16 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
In the instant case the claims recite the same subject matter, only changing the order of some alternative elements from “amount that is the same as, greater than, or less than” (claim 15) to “amount that is the same as, less than, or greater than” (claim 16).
Claim Rejections - 35 USC § 112 - Indefiniteness
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 12-19 and 21-25 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “variant”, with regard to TCL1A nucleic acid sequences in a subject is a relative term which renders the claim indefinite. Neither the claims, nor the specification make clear what is intended to be the standard for comparison for determining what nucleotide content is required or encompassed by the detected “variant”. This requirement is unclear where there are naturally occurring polymorphic difference in nucleotide content in the human population, and so any content may be a “variant” depending on the reference for comparison, which is not defined.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 5, 12 and 18 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Jaiswal et al (US PG Pub 2024/0067970, effective filing date 01/25/2021).
Relevant to the instant rejection, Jaiswal et al teaches that increased expression of TCL1A is associated with CHIP (e.g.: para 0007).
Relevant to claims 1 and 5, the reference includes methods of treating CHIP comprising administration of an agent that inhibits expression or activity (i.e.: an antagonist) of TCL1A (e.g.: claim 1 on p.62) and teaches RNA agents to decrease expression or activity including antisense and RNAi agents (e.g.: claim 2 and 3 on p.62). The reference further teaches the detection of TET2 driver mutations (e.g.: claim 9 on p.62), and teaches that TCL1A is of particular relevance to TET2-CHIP (e.g.: Figures 2 and 3).
Relevant to the rejection of claims 12 and 18, the reference teaches genotyping for alleles of rs2887399 and rs11846938 (e.g.: claims 7 and 8 on p.62; para 0067-0068).
Claim Rejections - 35 USC § 103
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(s) 1, 5, 12-16, 18-22, 24 and 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jaiswal et al (US PG Pub 2024/0067970, effective filing date 01/25/2021).
As detailed earlier in this Office Action with regard to claims 1, 5, 12 and 18, Jaiswal et al teaches methods including the treatment of a subject with TET2-CHIP with antagonist of TCL1A (including RNAi or antisense), and the genotyping of TCL1A (including rs2887399 and rs11846938) in the subject (also relevant to the limitations of claim 19, 24 and 25).
Jaiswal et al does not exemplify the administration of particular dosage amounts (e.g.: standard, or greater/less than standard) dependent upon TCL1A genotypes. However, Jaiswal et al does teach dosing regimens with different dosages (e.g.: para 0060), as well as treatments with agents other than TCL1A antagonists (e.g.: para 0118-0119) and combinations of treatments (e.g.: para 0077-0078), and teaches that TCL1A genotypes may be heterozygotes, alt-homozygotes and ref-homozygotes (e.g.: para 0196).
Where claims encompass the administration of treatments in a “standard dosage” in combination with a TCL1A antagonist, it would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have provided such administration of treatments to a subject based on the teachings of Jaiswal et al. The skilled artisan would have been motivated provide a standard treatment in combination with a TCL1A antagonist based on the expressed teachings of Jaiswal et al that a given therapeutic agent has a recommended dosing regimen (e.g.: para 0060; a standard dosage), and that therapeutics may include agents known in the art (e.g.: para 0118) in combination with a TCL1A antagonist (e.g.: claim 10 on page 62). Where Jaiswal et al teaches that increased expression of TCL1A is associated with increased clonal expansion, and the presence of an “alt-allele” (where an alt-allele may be a variant) of a particular SNP (i.e.: the T allele of rs2887399) leads to reduced TCL1A expression and reduced CHIP (para 0008; Fig 2B; Fig 4), it would be obvious to administer a standard dosage of, for example, Aranesp to any subject (e.g.: subject with the prese of a T allele at rs2887399, or subjects without the T allele at rs2887399) with CHIP (relevant to the requirements of claims 12-16, and claims 19-21). It would be further obvious to administer a TCL1A antagonist to a subject with at least one reference (i.e.: non-variant, non-alt-allele) copy of the TCL1A gene (i.e.: subjects where the variant is absent, or heterozygous subjects with one copy of the variant present) based on the expressed teachings of Jaiswal et al that the presence of the alt-allele (i.e.: T allele) at human SNP rs2887399 prevents accessibility of chromatin at the TCL1A promoter, leading to reduced expression. The skilled artisan would recognize that at least one wild type copy of the TCL1A gene leads to increased CHIP (e.g.: Fig 2B), and would be subject to treatment with an antagonist (e.g.: para 0009; Fig 4). The skilled artisan would have a reasonable expectation of success because Jaiswal et al teaches that drugs that increase hematocrit are suitable for treatment of CHIP (e.g.: para 0118), and that antagonists of TCL1A can be used to alter level of gene function (e.g.: para 0069-0074).
Claim(s) 17 and 23 are is/are rejected under 35 U.S.C. 103 as being unpatentable over Jaiswal et al (US PG Pub 2024/0067970, effective filing date 01/25/2021) as applied to claims 1, 5, 12-16, 18-22, 24 and 25 above, and further in view of ss3975531991 (2020).
Jaiswal et al renders obvious the detection of alleles of TCL1A (including rs2887399 and rs11846938) and the treatment of TET2-CHIP with an antagonist of TCL1A. Jaiswal et al does not teach genetic alterations of TCL1A that are frameshift mutations (e.g.: as recited in claims 17 and 23). However, such alterations were known in the prior art and are taught by ss3975531991.
The prior art disclosure of ss3975531991 provides a two nucleotide insertion (i.e.: a duplication of TC) identified as chr14:g.95714057_1, which is reference SNP rs1595068500 providing a frameshift mutation in the coding sequence of the TCL1A gene.
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have including detection of the presence or absence of ss3975531991 in the methods rendered obvious by Jaiswal et al. The skilled artisan would have been motivated to detect other alterations of TCL1A based on the expressed teachings of Jaiswal et al that TCL1A is associated with increased clonal expansion, and the teachings of Jaiswal et al that TCL1A protein has structures that are required for its biological functionality (e.g.: para 0065). Thus, where Jaiswal et al a promoter alteration that decreases TCL1A expression (e.g.: para 0008) associated with decreased clonal expansion, the skilled artisan would recognize that alterations of the encoded protein which decrease protein function would have the same protective effect, and that the lack of such an alteration (i.e.: the presence of a functional coding sequence) would indicate that the TCL1A gene is a target for treatment of CHIP in a subject with the functional TCL1A gene. The skilled artisan would have a reasonable expectation of success because ss3975531991 teaches that such a frameshift mutation is detectable in human samples.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683