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 .
Claim Status
In the reply on 01 June 2026 Applicant has amended claims 2-15; and withdrawn claims 16-28. Therefore, claims 1-28 are pending.
Election/Restrictions
Applicant’s election with traverse of Group 1, claims 1-15, drawn to a method for producing an animal model of metastasis, said method comprising: providing recombinant cancer cells obtained by transfecting the wild type cancer cells with a vector in the reply filed on 01 June 2026 is acknowledged.
Applicants traverse argues that the Examiner's restriction on the ground of a lack of "serious burden" on the Examiner. As set forth in the Manual of Patent Examining Procedure, the criteria for a restriction requirement include: (1) the inventions must be independent or distinct, and (2) there would be a serious burden on the Examiner if the restriction is not required. See M.P.E.P. §§ 802.02 and 803. Specifically, the Applicant stress that: If the search and examination of all the claims in an application can be made without serious burden, the examiner must examine them on the merits, even though they include claims to independent or distinct inventions (See remark filed 01 June 2026; p 5 last 2 ¶).
This is not found persuasive because MPEP states in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art. The examiner is able to provide art which satisfied the limitations of method of group I discuss as below, thereby demonstrating that the special technical feature lacks novelty. Therefore, a lack of unity exists between the restricted groups.
Claims 16-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-15 are under current examination.
Priority
This application was filed 01/29/2024 and is a 371 application of PCT/IN2022/050928 filed on 10/18/2022, which claims benefit to the foreign application IN202141061794 filed on 12/30/2021 and filing of a certified translated copy of the IN202141061794, filed 01/29/2024 is acknowledged (MPEP 2304.01(c)).
Thus, the earliest possible priority for the instant application is 12/30/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/29/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner and the signed and initialed PTO Forms 1449 are mailed with this action.
Claim Rejections - 35 USC § 112
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 12-13 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.
Dependent claim 12 is recited a limitation “wherein said mesenchymal marker is selected from N-Cadherin and Vimentin”. However, the independent claim 1 does not introduce “mesenchymal marker” limitation, therefore there is insufficient antecedent basis for this limitation.
Similarly, claim 13 is recited a limitation “epithelial marker is selected from E-cadherin and EpCam,” however, the independent claim 1 does not introduce “epithelial marker” limitation, therefore there is insufficient antecedent basis for this limitation.
Appropriate correction is required.
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)(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.
Anticipated by Spoelstra et al.
Claims 1, 14-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Spoelstra et al. (Cancer Res 2006; 66(7): 3893-902, cited in PTO892; hereinafter “Spoelstra”).
With respect to claim 1, and 14-15 Spoelstra discloses the transcription factor ZEB1 ([Symbol font/0x64]EF1 in mice) has been implicated in cellular processes during development and tumor progression including epithelial to mesenchymal transition (abstract). ZEB1 is normally regulated by both estrogen and progesterone receptors, but in uterine cancers, it is likely no longer under control of steroid hormone receptors and becomes aberrantly expressed in epithelial-derived tumor cells, supporting a role for ZEB1 in epithelial to mesenchymal transitions associated with aggressive tumors (abstract). Spoelstra teaches that the vector comprising a gene construct encoding a transcription factor of ZEB, and a bioluminescence gene to obtain transfectants capable of expressing said transcription factor by injecting wild-type C57BL/6 mice were ovariectomized at 5 to 6 weeks and rested for 2 weeks (p. 3894 left-side col. 3-5th ¶). Therefore, Spoelstra anticipates method of producing an animal model of metastasis by transfecting the wild type cancer cells with a vector comprising a gene construct encoding ZEB and implanting, orthotopically, said recombinant cancer cells into an immunodeficient mouse.
With respect to claims 1 and 14-15, it is noted that the claimed wherein clauses do not recite any additional active method steps, but simply state a function, characterization or measurement of the results of product positively recited (e.g., the plasticity ratio of 0. 7 to 1.2). The claimed recombinant cancer cells have the same structure as the cells of Spoelstra et al. and therefore would necessarily have the same characteristics. MPEP 2112.01(II) recites that if the composition is physically the same, it must have the same properties: "Products of identical chemical composition cannot have mutually exclusive properties. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present." Accordingly, in here the recombinant cancer cells of Spoelstra would have the plasticity ratio (PR) in the range of 0. 7 to 1.2.
Accordingly, Spoelstra anticipates the instant claims 1, and 14-15.
Anticipated by Wang et al.
Claims 1-4, and 8-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al. (Oncology Reports 39: 31-44, 2018, cited in PTO892; hereinafter “Wang”).
Regarding claims 1-4, and 14-15, Wang describes a liver metastasis model obtained by intra-splenic injection of the colon cancer cell lines SW480, HT29 and HCT116 transfected with TWIST and a GFP fluorescent gene into immunodeficient female BALB/c nude mice (10-11 weeks of age) (abstract, Fig. 3, p. 33 2nd ¶ or Wang). The mice show spontaneous liver, colorectal and spleen metastasis (Figures 10-12, p. 37 2nd ¶, p. 32 “Material and Methods” of Wang). Therefore, POSITA would anticipate that the bioluminescence gene to obtain transfectants capable of expressing said transcription factor TWIST; and implanting, orthotopically, said recombinant cancer cells (e.g., SW480, HT29) into an immunodeficient mouse.
Since the cells are transfected with TWIST as claimed, the cells inherently also have a plasticity ratio which is the same as in the application, i.e., which falls into the claimed PR range (see MPEP 2112.01(II)).
Regarding claims 8-9, Wang discloses that the vector comprises a constitutive promoter (i.e., mU6) and inducible promoter (i.e., shRNA) (abstract, p. 32 3rd ¶, Fig. 2 of Wang). MPEP 2112.01(II) recites that if the composition is physically the same, it must have the same properties: "Products of identical chemical composition cannot have mutually exclusive properties. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present." MPEP 2164.01(c) further states that “When a compound or composition claim is limited by a particular use, enablement of that claim should be evaluated based on that limitation. See In re Vaeck, 947 F.2d 488, 495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991) (claiming a chimeric gene capable of being expressed in any cyanobacterium and thus defining the claimed gene by its use).” Accordingly, in here the constitutive and inducible promoter of Wang would have the constitutive expression and regulating expression of the transcription factors.
Regarding claims 10-11, Wang discloses that the method allowing the recombinant cancer cells to metastasize for a suitable time period in the range of 20-30 days (3-4 weeks) (p. 33 2nd ¶, Fig. 10 of Wang).
Regarding claims 12-13, Wang discloses that the mesenchymal marker is selected from N-Cadherin and Vimentin and epithelial marker is selected from E-cadherin (abstract, p. 32 2nd ¶, p. 41 1st and 2nd ¶ of Wang).
Accordingly, Wang anticipates the instant claims 1-4, and 8-15.
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 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
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, 7, and 8-15 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (Oncology Reports 39: 31-44, 2018, cited in PTO892; hereinafter “Wang”), in view of Peinado et al., (Nature reviews cancer, 7(6), pp.415-428; cited in PTO892; hereinafter “Peinado”).
As discussed previously, Wang describes (regarding instant claims 1-4, and 8-15) a liver metastasis model obtained by intra-splenic injection of the colon cancer cell lines SW480, HT29 and HCT116 transfected with TWIST and a GFP fluorescent gene into immunodeficient female BALB/c nude mice (10-11 weeks of age) (abstract, Fig. 3, p. 33 2nd ¶ or Wang). The mice show spontaneous liver, colorectal and spleen metastasis (Figures 10-12, p. 37 2nd ¶, p. 32 “Material and Methods” of Wang). Therefore, POSITA would anticipate that the bioluminescence gene to obtain transfectants capable of expressing said transcription factor TWIST; and implanting, orthotopically, said recombinant cancer cells (e.g., SW480, HT29) into an immunodeficient mouse.
Still regarding claims 1 and 7, Wang does not specifically teach the transcription factor is SNAIL. However, such was known in the prior art.
Peinado discloses the expression patterns of SNAIL, ZEB and bHLH transcription factors in different human carcinomas, together with functional studies, indicate that the various factors have different roles during tumor progression, with a more prominent role for SNAIL in the induction of epithelial–mesenchymal transition (EMT; FIG. 1) in primary tumors, whereas the other factors are involved in maintaining the migratory phenotype (p. 416 “”at a glance” ¶, Fig. 4). Therefore, SNAIL and ZEB recruit specific chromatin-remodeling complexes supports a dynamic link between transcriptional repression and the epigenetic gene silencing of E-cadherin (encoded by CDH1) during tumor progression and epithelial–mesenchymal transition (EMT) (p. 424 1st ¶, p. 425 “Strategy: the interplay of different factors in cancer.” ¶).
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Accordingly, it would have been obvious to practice the method for producing animal model of Wang and include SNAIL transcription factors as taught by Peinado with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Peinado because it will influence of the tumor and components of its microenvironment on the dynamic control of EMT and the angiogenic response during tumor progression (p. 424 1st ¶, p. 425 “Strategy: the interplay of different factors in cancer.” ¶). The POSITA would have had a reasonable expectation of success in combining the teachings of Wang and Peinado because each of these teachings both successfully use transcription factor that downregulate the tumor progression. Therefore, the products and method as taught by Wang et al. in view of Peinado et al. would have been prima facie obvious over the products and method of the instant application. In regard to the reasonable expectation of success in doing so, include the transcription factor SNAIL of Peinado had a reasonable expectation of success since the steps thereof required no more than recombinant DNA and cell culture technology.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Subject matter free of art
Claims 5-6 are objected because art does not teach or reasonably suggest the SEQ ID NOs: 1-4 (see ABSS report filed 12 Jun 2026). Since claims 5-6 depend from rejected base independent claim 1. Therefore, claim 1 would be free of the art, if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is 571-272-0196. The examiner can normally be reached M-F 8-5 (EST).
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
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