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 .
Claims 1-4, 6-8, 10-16 and 18-19 are pending and are being examined on the merits.
Preliminary Amendment
The Preliminary Amendment filed May 10, 2024 has been entered.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-4, 6-8, 10-16 and 18-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-4, 6-8, 10-16 and 18-19 are directed to a genus of heritable cell markers. As
indicated in MPEP § 2163, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that 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.
In the instant case, the claims encompass a genus of heritable cell markers, lacking a structural limitation. The specification describes that heritable cell markers can be barcoded nucleic acids that provide a unique identifier (p. 35, ll. 9-14) and can include gene editing proteins such as CRIPSR/Cas (p. 39, ll. 35-36 through p. 40, ll. 1-3). Furthermore, the heritable cell markers can induce neoplastic cell formation. However, the instant application only discloses some gene editing proteins that may induce neoplastic cell formation. The specification does not show any other heritable cell marker other than generic definitions of a cell marker. The specification fails to describe any additional species by any relevant, identifying characteristics or properties other than by functionality (i.e., heritable cell marker).
The claims encompass a large genus of heritable cell markers, which are structurally/functionally unrelated. A sufficient written description of a genus of heritable cell markers may be achieved by a recitation of a representative number of heritable cell markers, or a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. However, in the instant case, there is no structural feature that is representative of all of the members of the genus of heritable cell markers recited in the claims, and there is no information as to a correlation between structure and function.
Because the specification only discloses a limited number of specific heritable cell markers of the genus and lacks description of any additional species by any relevant, identifying characteristics or properties, the ordinary artisan would not recognize from the disclosure that Applicant was in possession of the claimed invention.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 6-8, 11-13 and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Bhang (Studying clonal dynamics in response to cancer therapy using high-complexity barcoding, Nature Medicine, 21(5): 440-452, 2015) in view of Chenchik (US Patent App. Pub. No. 2013/0330730 A1).
Regarding independent claim 1, Bhang teaches …
A method of measuring population size for a plurality of clonal cell populations in the same tissue, the method comprising: (a) contacting a biological tissue with a plurality of cell markers that are heritable and distinguishable from one another, to generate a plurality of distinguishable lineages of heritably marked cells within the contacted tissue (Fig. 1a);
(b) after sufficient time has passed for at least a portion of the heritably marked cells to undergo at least one round of division, detecting and measuring quantities of at least two of the plurality of cell markers present in the contacted tissue, thereby generating a set of measured values (Fig. 1a);
and (c) calculating, using the set of measured values as input, a number of heritably marked cells present in the contacted tissue for at least two of said distinguishable lineages of heritably marked cells (Fig. 1a: monitoring counts per barcode).
Further, regarding the limitations requiring that the clonal cell populations are comprised within a tissue, Bhang suggests that the method could be used for such a purpose. Specifically, Bhang notes that studies applying the method to in vivo models would likely provide additional useful insights (p. 447, left col., para. 4). In addition, Chenchik teaches a similar method to Bhang in which a population of target cells are transduced with a packaged effector library, where each effector comprises, in part, a distinct clonal barcode (para. 8). The barcode construct is heritable by daughter cells during cell replication (para. 23). Chenchik specifically teaches performing the method in a tissue (para. 64).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Bhang method to apply it to cell populations comprised in tissues, as suggested by Bhang and as taught by Chenchik. The ordinary artisan would have been motivated to do so to achieve the expected advantage of having an assay that is capable of investigating additional cancer-related processes, as taught by Bhang (p. 447, left col., para. 4). The ordinary artisan would have had an expectation of success as Chenchik teaches a similar assay that is performed in cell populations comprised in tissues.
Regarding dependent claims 2-3, Bhang additionally teaches that the heritably marked cells within the contacted tissue are neoplastic cells (p. 441, left col., para. 2), as recited in claim 2, and that the tissue comprises neoplastic cells and/or tumors prior to step (a) (p. 441, left col., para. 2), as recited in claim 3.
Regarding dependent claim 4, Bhang additionally teaches that the detecting and measuring of step (b) is performed on a biological sample collected from the tissue (Fig. 1a: harvest select cell population).
Regarding dependent claim 6, Bhang additionally teaches that each cell marker of the plurality of cell markers corresponds to a known cell genotype for a lineage of heritably marked cells (p. 450, left col., bottom para.: samples were genotyped).
Regarding dependent claim 7, Bhang additionally teaches that the contacting comprises genetically altering cells of the tissue to generate the heritably marked cells (Fig. 1a: barcoding cells by lentiviral infection with a high-complexity DNA barcode library).
Regarding dependent claim 8, Bhang additionally teaches that the method is a method of measuring tumor size for a plurality of tumors of the same tissue (Fig. 1a: until a clonal population emerged).
Regarding dependent claim 11, Bhang additionally teaches that the detecting and measuring is performed after sufficient time has passed for tumors to form in the contacted tissue as a result of said contacting (Fig. 1a: until a clonal population emerged).
Regarding dependent claim 12, Bhang additionally teaches that the plurality of cell markers comprises barcoded nucleic acids (Fig. 1a).
Regarding dependent claim 13, Bhang additionally teaches that the detecting and measuring comprises high-throughput sequencing and quantification of the number of sequence reads for each detected barcode (Fig. 1a: PCR followed by next-gen sequencing).
Regarding dependent claim 18, Bhang additionally teaches that the barcoded nucleic acids are selected from: synthesized nucleic acid fragments (Fig. 1a).
Regarding dependent claims 18-19, Chenchik additionally teaches that the barcoded nucleic acids are selected from: plasmids and minicircles (paras. 18, 23), as recited in claim 18, and RNA molecules (paras. 9, 18, 23, 36), as recited in claim 19.
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to further modify the modified Bhang method, discussed above, to incorporate the Chenchik heritable nucleic acids. The ordinary artisan would have been motivated to try the Chenchik nucleic acids in order to customize the assay as needed through routine experimentation, and would have had an expectation of success as Chenchik teaches that such nucleic acids are suitable for that purpose.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4, 6-8, 10-16 and 18-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11, 20 and 22 of U.S. Patent No. 10,801,021 (hereinafter, the ‘021 patent).
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of the ‘021 patent teaches an embodiment of the instant claims 1 and 10 methods.
In addition, claims 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 20 and 22 of the ‘021 patent teaches all of the limitations of instant claims 4, 6, 7, 8, 11, 12, 13, 14, 15, 16, 18 and 19, respectively.
Modifying the ‘021 patent by re-arranging method steps to create different embodiments would have been prima facie obvious to the ordinary artisan, as they would have been motivated to optimize an embodiment through routine experimentation to customize the embodiment as needed for a particular assay. The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid assays are well-known in the art.
Conclusion
Claims 1-4, 6-8, 10-16 and 18-19 are being examined and are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN GREENE whose telephone number is (571)272-3240. The examiner can normally be reached M-Th 7:30-5:30 EST.
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/CAROLYN L GREENE/Examiner, Art Unit 1681