DETAILED ACTION
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 without traverse of species: DNA/RNA, R146* mutation, BAP1 gene and claim 90 in the reply filed on 10/8/2025 is acknowledged.
Claims 47, 89 and 91 are withdrawn from consideration as being directed to non-elected species. Claims 1-3, 45-46, 60, 64, 65, 72, 73, 76, 84, 86, 88, 90, 92, and 95 are under consideration in this office action.
Claim Rejections - 35 USC § 112
112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-3, 45-46, 60, 64, 72, 73, 76, 84, 86, 88, 90, 92, and 95 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention.
Relevant to the lack of particular structural limitations in the rejected claims drawn to inactivating PBRM1 mutations, MPEP 2163 states:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.
Additionally, at 2163IIA3(a), the MPEP states:
“…describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene “because it is only an indication of what the gene does, rather than what it is.”); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”).
The claims are broadly drawn to methods of treating or delaying progression of meningioma in individuals with “an inactivating” mutation of PBRM1.
In the case of the instant claims, the functionality of identifying inactivating PBRM1 mutations is a critical feature of the claimed methods.
The specification defines “inactivating mutation of PBRM1” at paragraph 0050 to be directed to “any mutation in a PBRM1-related nucleic acid or protein that results in reduced expression or activity of the PBRM1 protein.”. However, the specification does not provide any guidance as to which nucleic acids or proteins, other than PBRM1, would be considered a PBRM1 “related” sequence. The specification teaches identifying a number of specific intragenic deletions, frame shift insertions, frame shift deletions, and two truncating mutations (figure 1, table 1). However, the specification does not teach the effect of these mutations on PBRM1 function. Additionally, the specification does not teach or provide guidance as to the identity of mutations that are not in the PBRM1 gene or protein that are encompassed by the instantly pending claims.
While the general methodology of detecting mutations in nucleic acid targets is known, possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
The claims encompass a genus of structurally undefined mutations within PBRM1 or a PBRM1 “related” sequence, which require a specific functionality. This genus includes an enormous number of possible polymorphisms, missense mutations, truncations, insertions, deletions, frameshift mutations, etc. However, the specification does not provide guidance on identifying which of these possible mutations are in the claimed genus of “inactivating” PBRM1 mutations, from those that are not. Therefore, the skilled artisan would be unable to predictably correlate any other structural change in any other region of the PBRM1 gene, or any other sequence, with the claimed function
For claims drawn to a genus, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. Further, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“ [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
Thus considering the breadth of the polynucleotides required by the claimed methods, their specific required functionalities, and the teachings of the instant specification, it is the conclusion that the specification does not provide an adequate written description of the broadly claimed subject matter.
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.
Claims 1-3, 45-46, 60, 64, 65, 72, 73, 76, 84, 86, 88, 90, 92, and 95 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.
The claims recite the phrase “inactivating PBRM1 mutation”. However, other than teaching particular PBRM1 mutations, the specification does not provide any guidance on the which mutations within PBRM1 are “inactivating” vs those that are not. Additionally, at paragraph 0050, the specification teaches that “inactivating mutation of PBRM1” refers to “any mutation in a PBRM1 related nucleic acid”. However the specification provides no guidance as to the identity of PBRM1 related nucleic acids. Accordingly, the metes and bounds of the claims are unclear.
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.
Claims 1-3, 45-46, 60, 64, 65, 72, 73, 76, 84, 86, 88, 90, 92, and 95 are rejected under 35 U.S.C. 103 as being unpatentable over Williams (Williams et al; Acta Neuropathologica, vol 140, pages 89-93; May 13, 2020).
With regard to claims 1-3, Williams teaches human (claim 95) meningioma subjects with inactivating PBRM1 mutations (abstract, page 89-90, table 1), detected by CGP on hybridization captured, adaptor ligation-based libraries (claims 45-46). Williams teaches detecting allelic loss as well as truncation, frameshift, etc mutations including R146* (claims 60, 64, 65). Williams teaches obtaining tumor tissue (claims 72, 73, and 76). Williams teaches detecting additional mutations in BAP1 (page 92)(claims 84, 86). Williams teaches analysis of histologic features of the tumors, including detecting papillary and heterogenous features (claims 88, 90, and 92). With regard to claim 1, although Williams does not teach whether the subjects analyzed had been treated for meningioma, Williams does teach to treat meningioma (page 89, col 1). Therefore, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date, to have administered an anticancer agent to the meningioma patients taught by Williams, for the obvious benefit of treating the patients, as taught by Williams.
Claims 1-3, 45, 46, 60, 72, 73, 76, 84, 86, 88, 92 and 95 are rejected under 35 U.S.C. 103 as being unpatentable over Collord (Collord et al; 2018; Nature Scientific Reports; 8:13537, pages 1-13).
With regard to claims 1-3, Collord teaches human (claim 95) meningioma subjects with inactivating PBRM1 mutation (abstract, page 3, figure 1), detected by NGS (pages 7-13) (claims 45-46). Collord teaches detecting allelic loss (claims 60). Collord teaches obtaining tumor tissue (claims 72, 73, and 76). Collord teaches detecting additional mutations in CDKN2A (page 93, figure 1) (claims 84, 86). Collord teaches analysis of histologic features of the tumors, including detecting papillary (see whole documents) and heterogenous features (claims 88, 90, and 92). With regard to claim 1, although Collord does not teach whether the subjects analyzed had been treated for meningioma, Collord does teach to treat meningioma (page 1). Therefore, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date, to have administered an anticancer agent to the meningioma patients taught by Collord, for the obvious benefit of treating the patients.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to examiner Jehanne Sitton whose telephone number is (571) 272-0752. The examiner is a hoteling examiner and can normally be reached Mondays-Fridays from 8:00 AM to 2:00 PM Eastern Time Zone.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Winston Shen, can be reached on (571) 272-3157. The fax phone number for organization where this application or proceeding is assigned is (571) 273-8300.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1682