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In the reply on 24 July 2026 Applicant has amended claim 107, and claims 118-126 are withdrawn.
Therefore, claims 107-126 are pending in this application.
Election/Restrictions
Applicant’s election without traverse of Group I: Claims 107-117, directed to heterogeneous IFN-gamma primed cell composition comprising mesenchymal progenitor cells and epithelial progenitor cells and use thereof in the reply filed on 24 July 2026 is acknowledged.
Claims 118-126 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 107-117 are herein under examination.
Priority
This application was filed 05/02/2024 and is a 371 application of PCT/US2022/048067 filed on 10/27/2022, which claims benefit to the Provisional Application 63263548 and 63263550 filed on 11/04/2021. Thus, the earliest possible priority for the instant application is 11/04/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/02/2024 and 07/24/2026 are 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 107 and 114-115 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 107 is recited a limitation “wherein the mesenchymal progenitor cells and epithelial progenitor cells are co-cultured.” However, the claim 107 only introduce “a population of feline or canine uterine-derived epithelial progenitor cells,” therefore, it is not clear whether the recited “epithelial progenitor cells” refer to the same “canine uterine-derived epithelial progenitor cells” or to a distinct cell population. Accordingly, the metes and bounds of claimed invention cannot be determined with reasonable certainty and indefinite. The rejection may be obviated by amending the claim 107 to recite: wherein the mesenchymal progenitor cells and the epithelial progenitor cells are co-cultured … wherein the mesenchymal progenitor cells and the epithelial progenitor cells are in a ratio of… wherein the mesenchymal progenitor cells and the epithelial progenitor cells are primed with IFN-gamma. Appropriate correction is required.
Claims 107 and 115 recite that the ratio is at least ratio of about 20% to about 80%, about 40% to about 60%, about 50% to about 50%, about 60% to about 40%, or about 80% to 20%. Claim 107 further recited “ratio within a range defined by any two of the aforementioned percentages.” The limitation of “about” and “any two of the aforementioned percentages” have rendered indefinite by reference to term of degree as stated in MPEP 2173.05 (b); In determining the range encompassed by the term "about", one must consider the context of the term as it is used in the specification and claims of the application. Ortho-McNeil Pharm., Inc. v. Caraco Pharm. Labs., Ltd., 476 F.3d 1321, 1326, 81 USPQ2d 1427, 1432 (Fed. Cir. 2007). In the instant case, the specification does not provide a standard for measuring that degree (i.e., what constitutes “about”). See SPEC [0231] ¶ of US20250019662A1. Accordingly, the specification is not considered to provide an adequate standard for measuring the degree of what constitutes “about”. Appropriate correction is required.
Claim 114 contains the trademark/trade name “CryoStor” and “BioLife Solutions”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, “CryoStor” and “BioLife Solutions” are used in cryopreservation medium, however these trademark represents the source of product rather than the identify the product composition or details. Accordingly, the trademark description is indefinite (see MPEP 608.01(v)). Therefore, appropriate correction is required.
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 107-117 are rejected under 35 U.S.C. 103 as being unpatentable over Phan et al. (US20180119103A1; cited in IDS filed 05/02/2024; hereinafter "Phan") in view of Sahoo et al. (Veterinary world, 10(12), p.1533, 2017; cited in IDS filed 05/02/2024; hereinafter "Sahoo") and Guess et al. (Stem cells translational medicine, 6(10), pp.1868-1879, 2017; cited in IDS filed 05/02/2024; hereinafter "Guess") as evidenced by Nisolle (Fertility and Sterility, 64:1, 69-75, 1995; cited in PTO892; hereinafter “Nisolle”).
Regarding claims 107 and 116-117, Phan teaches a heterogeneous cell composition comprising: a population of mesenchymal progenitor cells and epithelial progenitor cells ([0002], [0099]-[0101] of Phan), Phan further provides the use of a skin equivalent of the present invention or a skin equivalent obtained by the method of the present invention for the manufacture of a pharmaceutical composition as well as the pharmaceutical composition; wherein the mesenchymal progenitor cells and epithelial progenitor cells are co-cultured ([0002], [0083] of Phan) for promoting wound healing, skin repair, regeneration, rejuvenation [0267] and multiple sclerosis [0261].
Phan does not teach wherein the mesenchymal progenitor cells and epithelial progenitor cells are obtained or derived from canine or feline uterine tissue, cells ratio and epithelial progenitor cells are primed with IFN-gamma.
Sahoo teaches progenitor cells are obtained or derived from canine uterine tissue (abstract, p. 1533 col 1 1st ¶ of Sahoo). The unlimited proliferative and developmental potential of endometrial stem cells offer considerable opportunity for applications in regenerative medicine and tissue engineering (p. 1539 col 2 2nd ¶ of Sahoo). Furthermore, relating to Mesenchymal cells, Guess teaches, the mesenchymal cells are primed with IFN-gamma to improve handling and biocompatibility (abstract, p. 1868 1st ¶ of Guess).
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 heterogeneous cell composition of Phan (X) and include progenitor cells are obtained or derived from canine uterine tissue and primed with IFN-gamma with a reasonable expectation of success as taught by Sahoo and Guess. One of ordinary skill would have been motivated to do so as taught by Sahoo and Guess because the mesenchymal cells are primed with IFN-gamma to improve handling and biocompatibility (abstract, p. 1868 1st ¶ of Guess). Therefore, it would have been obvious to one of ordinary skill in the art to combine these references and provide a canine uterine derived IFN-y primed mesenchymal progenitor cells and epithelial progenitor cells by routine experimentation to optimize handling and producing the therapeutic cells of Phan.
Phan further teaches the expansion of umbilical cord epithelial and mesenchymal stem cells using repetitive tissue explants of umbilical cord lining membrane tissues. MPEP § 2144.05 states that “Generally, differences in concentration by adjusting solution will not support the patentability of the subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation" In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955).” Therefore, it would have been obvious to one of ordinary skill in the art to combine these references and provide a canine uterine derived IFN-y primed mesenchymal progenitor cells and epithelial progenitor cells in a ratio of 20% to 80% to about 80% to 20% by routine experimentation to optimize producing the therapeutic cells of Phan.
Regarding claim 108, Phan teaches that the FGF-2 is recombinant human FGF-2 [0002]. FIG. 9-12 shows Western blot analysis by which the expression of FGF-2 in UCEC and UCMC isolated according Phan [0053], [0193].
Regarding claim 109, Phan teaches that the cellular extract contains growth factors and peptides and is in the form of a supernatant into which the epithelial or mesenchymal stem/progenitor cells secrete the growth factors [0053]. FIG. 9-12 shows Western blot analysis by which the expression of FGF-2 in UCEC and UCMC isolated according Phan. In one embodiment, Phan discloses the medium contain 10 ng/ml epidermal growth factor (EGF) [0118]. Although, Phan does not teach wherein the FGF-2 is present at a concentration of 8 ng/mL. However, MPEP 2144.05(I) stated that “a prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).” Therefore, it would have been obvious to one of ordinary skill in the art to modify the amount of FGF-2 present such as 8 ng/mL by routine experimentation to control amounts of expressed growth factors present in the composition.
Regarding claims 110 and 111, Phan teaches that the composition is not pre-treated with cell-based feeder layers [0192], further composition was cultured in growth media until 100% confluence (37° C., 5% CO2) and then synchronized in starvation medium (serum-free DMEM) for 48 hours ([0194] of Phan).
Regarding claim 112, examiner interprets “transit-amplifying" (TA) cell are found in epithelial tissues (see instant SPEC [0199] ¶) and further interprets such cells are capable of expressing marker associated with both mesenchymal progenitor cell and epithelial progenitor cell. Phan teaches that the isolation of the stem/progenitor cells from umbilical cord tissue, the umbilical cord or a part thereof is usually collected immediately after birth and for transport to the laboratory transferred in a medium that is suitable for handling of mammalian tissue [0089-0090]. Phan further teaches the cells derived from stem/progenitor cells are mesenchymal stem cells (UCMC) or epithelial stem cells (UCEC) [0100]. Accordingly, POSITA at the time of invention would have reasonably expected that a stem/progenitor cells population isolated from umbilical cord tissue exhibiting marker associated with both UCMC and UCEC cells.
Regarding claims 113 and 114, Phan teaches that the composition further comprises cryopreservation medium [0090-0091] comprises DMSO [0091] and 10% FCS [0119] in growth medium. MPEP § 2144.05 states that “Generally, differences in concentration by adjusting solution will not support the patentability of the subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation" In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955).” Therefore, it would have been obvious to one of ordinary skill in the art to combine these references and provide a canine uterine derived IFN-y primed mesenchymal progenitor cells and epithelial progenitor cells in 1-10% DMSO by routine experimentation to optimize producing the therapeutic cells of Phan.
Although regarding claim 115, Phan is silent to the cell composition comprises a population of vimentin-positive (V+)/cytokeratin-negative (C-) cells. However, such was known in the prior art.
Regarding the inherency and product claims MEPE 2112.01(I) states that “when the structure taught by the reference is identical or substantially identical to that of the claims, the claimed properties or functions are presumed to be inherent”. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). MPEP 2112.01 (II) also states that for composition of matter claims, if the composition is physically the same, it must have the same properties. In re Spada, 15 USPQ2d 1655, 1658 (Fed Cir 1990). Furthermore, MPEP 2112.01 states that where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103. In here, Nisolle taught taking uterine biopsies at different cycle stages including proliferative, early secretory and late secretory (para bridging pages 69-70). Cells were assessed for cytokeratin and vimentin expression. It was found that as the cycle progressed, the expression of vimentin (mesenchymal progenitor marker) and cytokeratin (epithelial progenitor marker) cycled as well. Thus, Nisolle taught the [AltContent: textbox ([img-media_image1.png])]number of V+/C+ (MPCs) and V+/C- (EPCs) cells present in the uterus varies. Nisolle teaches vimentin and cytokeratin are coexpressed in the epithelial cells (page 74). Thus, in the early secretory phase, 23.5% of the cells are V+C+ and 26.1% (49.6-23.5) are V+C-. which falls within the claimed ratio requiring each cell type be within 4-fold of the other.
With regard to claim 115, where the ratio of MPC:EPC (V+C-:V+C+) is at least about 2:3 (M:E>0.667), that ratio is met by any of the ratios in Table 1 of Nisolle. With regard to claims 113 and 116 where the ratio of MPC:EPC (V+C-:V+C+) is at least about 3:2 (M:E>1.5), and claims 114 and 117 where the ratio of MPC:EPC (V+C-:V+C+) is at least 4, those ratios are met by the late secretory phase ratio in Table 1 (5.23) of Nisolle.
While Nisolle teaches ratios of cells in human uteri, it would be reasonable to expect that similar cycling ratios would be present in dogs and cats and within the cycle, at some point, the ratios of cells would be within 4-fold of one another as claimed. Thus, Nisolle is relied upon as evidence that the recited ratios are present in dog and cat uteri. Accordingly, POSITA at the time of invention would have reasonably expected that cell composition comprises a population of vimentin-positive (V+)/cytokeratin-negative (C-) cells; and a population of V+/cytokeratin-positive (C+) cells.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
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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