DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant's amendment and remarks filed on 12/19/2025 are acknowledged.
Claims 1-20 are pending.
3. Applicant’s election without traverse of the invention of Group I (claims 1-6) in the reply filed on 12/19/2025 is acknowledged.
Claims 7-20 are withdrawn from further consideration by the Examiner under 37 C.F.R. § 1.142(b) as being drawn to nonelected inventions.
Claims 1-6 are presently under consideration.
4. Applicant's claim for domestic priority under 35 U.S.C. 119(e) to provisional application USSN 63/394,929 is acknowledged.
Provisional application USSN 63/394,929 fails to provide adequate support under 35 U.S.C. 112 for claims 1-6 of the present application. Specifically, neither the specification nor the claims provide support for at least the method steps of claim 1.
It is noted that the file of the USSN ‘929 application contains two documents titled “Appendix,” one of which appears to be identical to the document listed as NPL #2 on IDS filed on 08/03/2023 in the present application, identified as “YAMAMOTO et al.; "Peri-necrotic Angiopectin [sic]-like 7 regulates circulating tumor cell dissemination" manuscript submitted to PNAS Cell Biology on May 10, 2022; pp. 1-36, later published as NPL 1 above.”
In the absence of indication that the documents titled “Appendix” are part of the disclosure of the USSN ‘929 application, or are incorporated by reference into the disclosure, presently pending claims have been accorded the priority of the filing date of the instant application, i.e. 08/03/2023. Should Applicant disagree with the above Examiner’s determination, it is incumbent upon Applicant to provide a showing that adequate supports the presently claimed subject matter as required by 35 U.S.C. 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.
6. Claims 1-6 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
(i) Claim 1 is indefinite in the recitation of a “biological sample,” because the nature of the sample (e.g. urine, saliva, etc.) is not defined.
(ii) Claim 1 is further indefinite in the recitation of a “CTC reference level,” because the reference level is not defined.
(iii) Claim 1 is further indefinite because the inconsistency between the preamble and the resolution of the claimed method. The preamble recites a method of “inhibiting” necrotic core formation in a tumor to “reduce the risk” of metastatic dissemination from the tumor core, whereas the resolution states that the method would “reduce” necrotic core formation and “prevent” metastatic dissemination. “Inhibiting” necrotic core formation is not equivalent in scope to “reducing” necrotic core formation, and “reducing the risk” of metastatic dissemination is not equivalent in scope to “preventing” metastatic dissemination.
(iv) Claim 1 is further indefinite because of multiple ambiguities in the recitation of method steps (a) and (b). The steps include determining CTC level, comparing it to a reference, and if the level is not greater than the reference, repeating the determining and comparing until the level is greater than the reference. The following aspects of the claimed method are unclear:
(A) The frequency of “repeating” is not defined. Are the steps repeated every few minutes, hours, etc.?
(B) The claim calls for repeating the step of determining CTC level in a sample, but does not provide for obtaining a new sample, i.e. it reads on repeated determining CTC level in the same sample.
(C) Practicing the method as claimed is predicated on the assumption that at some point CTC level exceeds the reference, but it is unknown what happens if it does not. Are the steps of “determining” and “comparing” repeated ad infinitum?
(D) Importantly, it is unknown what happens to the subject patients while the steps of “determining” and “comparing” are being repeated. Do they receive any treatment at all?
(v) Claims 2, 4 and 5 are indefinite in the recitation of “Angptl7 antibody,” because it is unclear whether Angptl7 is the name of the antigen to which the antibody binds, or the name of the antibody itself. It is suggested that the claims be amended to recite “anti-Angptl7 antibody” to avoid the ambiguity.
(vi) Claim 4 is indefinite, because the recitation of “the [anti-]Angplt7 antibody” lacks proper antecedent basis in claim 1 on which claim 4 depends.
(vii) Claims 2-6 are indefinite, because they encompass the indefinite limitations of the claim(s) on which they depend.
In view of the above, a person of ordinary skill in the art cannot unequivocally interpret the metes and bounds of the claims so as to understand how to avoid infringement. Applicant is reminded that any amendment must point to a basis in the specification so as not to add New Matter. See MPEP 714.02 and 2163.06.
7. 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.
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 of this title, 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.
8. Claims 1-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by, or, in the alternative, under 35 U.S.C. 103 as obvious over Yamamoto et al. (02/28/2023; cited on IDS).
As addressed in section 4 above, instant claims are accorded the priority date of 08/03/2023; therefore, Yamamoto constitutes prior art relative to instant claims.
Yamamoto teaches that initiation of metastatic dissemination, manifested as a sharp rise in CTC, is associated with necrosis and vascular remodeling in the tumor core dependent on Angptl7, and Angptl7 inhibition reduces CTC and metastases (e.g. the Abstract).
The experimental procedures described by Yamamoto include all the limitations of claims 1 and 3, i.e. determining CTC level in blood samples of tumor-bearing rats, classifying the level as low or high (“Low-to High CTC Transition,” p. 2), which involves comparing the level to a reference which defines the difference between “low” and high CTC, and inhibiting Angptl7 expression with shRNA hairpin (p. 4), which is within the scope of “administering an Angptl7 inhibitor.”
Claim 2 is included in the rejection because a skilled artisan would at once envisage anti-Angptl7 antibody as the most common type of clinically useful inhibitor. Claim 4 is included, because therapeutic antibodies are typically administered intravenously, as a person of skill in the art would be aware. Claim 5 is included, because optimizing antibody administration regimen is routine in the art. Claim 6 is included, because cancer patients are treated with anti-cancer therapeutic agents, and because the claimed method is aimed at reducing metastatic dissemination but does not address treatment of the core tumor.
9. The following prior art and other documents are cited of record as pertinent to the present invention:
US 20180105563 (e.g. [0005])
US 20250296996 (e.g. [0055])
Lim et al. (2015) Cd11b(+) myeloid cells support hepatic metastasis through down-regulation of angiopoietin-like 7 in cancer cells. Hepatology, Vol. 62, No. 2, pp. 521-533.
Parri et al. (2014) Angiopoietin-like 7, a novel pro-angiogenetic factor over-expressed in cancer. Angiogenesis, Vol. 17, No. 4, pp. 881-896.
10. Conclusion: no claim is allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ILIA I OUSPENSKI whose telephone number is (571)272-2920. The examiner can normally be reached 9 AM - 5:30 PM.
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/ILIA I OUSPENSKI/ Primary Examiner, Art Unit 1644