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 .
DETAILED ACTION
1.Applicants’ election without traverse of group I (claims 1-20) in the reply filed on July 31, 2026 is acknowledged.
Status of the Application
2. Claims 1-20 are considered for the examination. Claims 21-24 are withdrawn from further consideration as being drawn to nonelected group.
Priority
3. This application filed on May 01, 2024 is a 371 of PCT/US2022/048442 filed on October 31, 2022, which claims priority benefit of US 62/399,329 filed one August 19, 2022 and US 63/274,741 filed on November 02, 2021.
Informalities
4. The following informalities are noted.
(i) claims 1-3 recite the terms ‘RNAs, RAS, KRAS, KRAs(G12C)’; claim 10 recites CRISPR; Claim 17 recites expression of ‘BNIP3, NUSAP1…….UBE2C’. Expanding the terms at least for the first time that they appear in the claims is suggested.
(ii) Claims 10 and 17 recite improper Markush group. Amending the claim to recite ‘selected from the group consisting of’ is suggested. Appropriate correction is required.
Claim Rejections - 35 USC § 112
5. 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.
A. Claim 3 is 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. Claim 3 recites ‘KRAS(G12C)’. The limitation enclosed within the parenthesis is unclear and indefinite because it is not clear if the limitation in the parenthesis is a required limitation or does it represent as an example.
B. Claims 6-8 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. Claims 6-8 recite the limitation "the extracellular vesicles" in line 2 of the claims. There is insufficient antecedent basis for this limitation in the claim because the claim 1 upon which the claims 6-8 depend lacks support for the limitation and it is not clear what the limitation is referring to.
Claim Rejections - 35 USC § 102
6. 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
A. Claims 1-11, 14-16 and 18-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Skog et al. (US 2015/0322532).
Skog et al. each a method for detecting a RAS pathway mutation in a subject comprising: (a) obtaining a biological sample from the subject (para 0007-0008); (b) isolating nucleic acids from the biological sample (para 0007-0008); and (c ) analyzing the expression level of the extracellular RNAs in the nucleic acids, wherein a differential expression level of the extracellular RNAs compared to a control sample indicates that the subject has a RAS pathway mutation (para 0007-0008, 0021, 0055-0056, 0061-0072, 0110).
With reference to claims 2-3, Skog et al. teach that the RAS pathway mutation is in KRAS and the mutation is KRAS(G12C) (para 0012, 0007-0008, 0040).
With reference to claims 4-5, Skog et al. teach that the biological sample comprises extracellular vesicles isolated from biofluids from the subject, wherein the biofluids comprise blood or serum (para 0014, 0061, 0007-0008).
With reference to claims 6-8, Skog et al. teach that the extracellular vesicles comprise exosomes or microvesicles, wherein the extracellular vesicles are greater than 200nm in size or less than 200nm in size (para 0106).
With reference to claim 9, Skog et al. teach that the nucleic acids comprise polyadenylated RNAs (para 0128).
With reference to claim 10, Skog et al. teach that the analyzing the expression level of extracellular RNAs comprises performing RT-PCR (para 0021, 0055-0056).
With reference to claims 11, Skog et al. teach that the analyzing the expression level comprises performing sequencing, (para 0125).
With reference to claim 14-16, Skog et al. teach that isolating the nucleic acids comprises isolating extracellular vesicles from the biological sample followed by isolating the nucleic acids from extracellular vesicles, wherein the nucleic acids are extracellular RNAs from the extracellular vesicles and the method further comprises repeating the steps (a) to (c) (para 0061-0066, 0026-0045 0106, 0110).
With reference to claims 18-20, teach that the subject has or is suspected of having cancer, wherein cancer is RAS mutant cancer, which is a lung cancer (para 0153, 0013). For all the above the claims are anticipated.
B. Claims 1-10, 14-15 and 17-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee et al. (US 2018/0216170).
Lee et al. each a method for detecting a RAS pathway mutation in a subject comprising: (a) obtaining a biological sample from the subject (para 0010, 0051); (b) isolating nucleic acids from the biological sample (para 0010, 0051); and (c) analyzing the expression level of the extracellular RNAs in the nucleic acids, wherein a differential expression level of the extracellular RNAs compared to a control sample indicates that the subject has a RAS pathway mutation (para 0010,0062).
With reference to claims 2-3, Lee et al. teach that the RAS pathway mutation is in KRAS and the mutation is KRAS(G12C) (para 0062, 0082).
With reference to claims 4-5, Lee et al. teach that the biological sample comprises extracellular vesicles isolated from biofluids from the subject, wherein the biofluids comprise blood or serum (para 0063).
With reference to claims 6-8, Lee et al. teach that the extracellular vesicles comprise exosomes or microvesicles, wherein the extracellular vesicles are greater than 200nm in size or less than 200nm in size (para 0051).
With reference to claim 9, Lee et al. teach that the nucleic acids comprise polyadenylated RNAs (para 0064).
With reference to claim 10, Lee et al. teach that the analyzing the expression level of extracellular RNAs comprises performing RT-PCR (para 0074, 0089-0090).
With reference to claim 14-15, Lee et al. teach that isolating the nucleic acids comprises isolating extracellular vesicles from the biological sample followed by isolating the nucleic acids from extracellular vesicles, wherein the nucleic acids are extracellular RNAs from the extracellular vesicles (para 0010-0014).
With reference to claim 17, Lee et al. teach gene expression comprising GAPDH (para 0077).
With reference to claims 18-20, Lee et al. teach that the subject has or is suspected of having cancer, wherein cancer is RAS mutant cancer, which is a lung cancer (para 0064). For all the above the claims are anticipated.
Claim Rejections - 35 USC § 103
7. 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-16 and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Skog et al. in view of Nagy et al. (Int. J. Cancer, Vol. 140, p. 930-937, (2017).
Skog et al. teach a method for detecting a mutation in Ras pathway in a subject as discussed above. However, Skog et al. did not teach obtaining one or more sequencing reads of the extracellular RNAs and aligning the sequencing reads to repetitive sequences in human genome.
Nagy et al. teach a method for detecting Kras mutations in a sample, wherein the method comprises exome RNA sequencing and aligning sequence data with repetitive sequences in human genome (page 931-934, paragraphs under ‘methods’ section).
It would have been prima facie obvious to one skilled in the art before the effective filing date of the invention to modify the method of Skog et al. aligning sequencing reads as taught by Nagy et al. to develop a sensitive method for detecting Kras mutation. The ordinary person skilled in the art would have motivated to combine the method of Skog et al. with aligning sequencing reads as taught by Nagy et al. and have a reasonable expectation of success that the combination would improve the sensitivity of detecting Kras mutation in a sample because Nagy et al. explicitly taught the analyzing sequencing data in comparison to human genome SNP reference accurately detect the sequence variations per gene (page 932, paragraphs under the section ‘statistical analysis pipeline) and such a modification of the method is considered obvious over the cited prior art.
Conclusion
No claims are allowable.
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Suryaprabha Chunduru
Primary Examiner
Art Unit 1681
/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681
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