DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendments
Applicant's amendments filed 11/03/2025 to claim 34 has been entered. Claims 2-18, 25-33, 36, and 37 are canceled. Claims 1, 19, 34, 35, and 38-55 remain pending, of which claims 34, 35, 38, and 39 are being considered on their merits. Claims 1, 19, and 38-55 remain withdrawn from consideration. References not included with this Office action can be found in a prior action.
The instant Declaration under 37 C.F.R. § 1.130 is persuasive to disqualify Rosado-Olivieri et al. (of record) as Applicant’s own work under the 35 U.S.C. § 102(b)(1) exception, as Rosado-Olivieri was published less than a year before the effective filing date of the Application. The rejection of claims 34, 35, 38, and 39 by Rosado-Olivieri under 35 U.S.C. § 102(a)(1) is withdrawn.
Any rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 34, 35, 38, and 39 are rejected under 35 U.S.C. 101 because the claimed invention is directed to natural product without significantly more.
Independent claim 34 recites a natural product, i.e. generic cells that are PDX1+ and NKX6.1+, in-combination with a verteporfin, a species of YAP inhibitor, and a concentration of 0.3-0.4 µM. Claims 35, 36, 38, and 39 depend from claim 34. At this time, there is no evidence that the claimed cells possess any markedly different characteristic as compared to the natured-based product itself. See M.P.E.P. § 2106.04(c).
This judicial exception is not integrated into a practical application because the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. Adding verteporfin is routine and conventional in this art. For example, see the teachings of Cebola et al. (Nature Cell Biology (2015), 17(5), 615-626 plus appended Methods and Supplementary Data). Cebola teaches a composition comprising pancreatic multipotent progenitor cells (MPCs) contacted with verteporfin (VP), wherein the pancreatic multipotent progenitor cells are PDX1+ and NKX6.1+ (2nd page of the Methods, right column, paragraph starting “VP experiments in….”; p616, left column, paragraph starting “To study the genomic…”). Cebola teaches that verteporfin disrupts the TEAD-YAP complex and uses verteporfin to study the effect of YAP inhibition on TEAD1-bound enhancers (p622, left column, paragraph starting “To study YAP-dependent…”).
Claim 35 further recites NGN3+ cells. Cell marker expression is an inherent property of the natural product, i.e. the cells of claim 34, and the claim does not recite any additional elements that are sufficient to amount to significantly more than the judicial exception beyond what is already recited in claim 34 and addressed above.
For claims 38 and 39, the judicial exception is not integrated into a practical application because the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. Adding ALk5 inhibitor II (i.e. Alk5i) is routine and conventional in this art. For example, see the teachings of Millman et al. (WO 2019/222487). Millman teaches methods and compositions for generating endodermal lineage cells and beta cells (Abstract). Millman teaches beta cells derived from stem cells (SC-β) that are PDX1+, NKx6.1+, and NGN3+ (p37, paragraph starting “Combining these modifications…”; also, p7, lines 23-27). Millman teaches adding ALk5 inhibitor II during the last stage of culture to mature the stem cell-derived beta cells (p19, lines 4-10), reading on claims 38 and 39.
For the reasons given above, claims 34, 35, 38, and 39 are found patent ineligible under 35 U.S.C. § 101.
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.
The factual inquiries 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 34 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Cebola et al. (Nature Cell Biology (2015), 17(5), 615-626 plus appended Methods and Supplementary Data).
Cebola teaches a composition comprising pancreatic multipotent progenitor cells (MPCs) contacted with verteporfin (VP), wherein the pancreatic multipotent progenitor cells are PDX1+ and NKX6.1+ (2nd page of the Methods, right column, paragraph starting “VP experiments in….”; p616, left column, paragraph starting “To study the genomic…”), anticipating claims 34 and 36. Cebola further teaches the MPCs are NGN3+ (Fig. 6d, “NGN3”). In a separate embodiment, Cebola teaches contacting E11.5 mouse embryonic pancreatic bud explants with 0.1 µM verteporfin (2nd page of the Methods, right column, paragraph starting “Pancreatic explant experiments…”), reading in-part on claim 34. Cebola teaches that verteporfin treatment of human in vitro MPCs and pancreatic bud explants dissected from E11.5 mouse embryos and grown ex vivo caused decreased expression of a subset of genes associated with TEAD1-bound enhancers (p622, left column, paragraph starting “To study YAP-dependent TEAD function…”), reading in-part on claim 34.
Regarding claim 34, Cebola does not teach adding 0.3-0.4 µM of verteporfin. However, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature 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). Also see M.P.E.P. § 2144.05 (II) and (III). In the instant case, Cebola teaches that the verteporfin concentration is a result effective variable to decrease expression of a subset of genes associated with TEAD1-bound enhancers in either pancreatic multipotent progenitor cells or in mouse embryonic pancreatic buds. Thus, the burden is shifted back to establish criticality of the claimed verteporfin concentration range by objective evidence.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 34, 35, 38, and 39 rejected under 35 U.S.C. 103 as being unpatentable over Millman et al. (WO 2019/222487) in view of Cebola et al. (Nature Cell Biology (2015), 17(5), 615-626 plus appended Methods and Supplementary Data).
Millman teaches methods and compositions for generating endodermal lineage cells and beta cells (Abstract). Millman teaches beta cells derived from stem cells (SC-β) that are PDX1+, NKx6.1+, and NGN3+ (p37, paragraph starting “Combining these modifications…”; also, p7, lines 23-27), reading in-part on claim 34 and 35. In a separate embodiment, Millman teaches adding verteporfin to methods of differentiating stem cells into beta cells because verteporfin is a YAP inhibitor and YAP inhibition enhances differentiation of human pluripotent stem cells to cells of endodermal lineage, pancreatic progenitors, and insulin-producing beta-cells (paragraph spanning p19-20), reading on claims 34 and 36. Millman teaches adding ALk5 inhibitor II during the last stage of culture to mature the stem cell-derived beta cells (p19, lines 4-10), reading on claims 38 and 39.
Regarding claim 34, it would have been obvious to a person of ordinary skill in the art before the invention was filed to add the verteporfin of Millman to the stem cell differentiation methods and composition of Millman. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Millman expressly considers the addition of verteporfin. The skilled artisan would have been motivated to do so because Millman teaches that adding verteporfin is predictably advantageous to improve differentiation of human pluripotent stem cells to cells of endodermal lineage, pancreatic progenitors, and insulin-producing beta-cells.
Regarding claim 34, Millman does not teach adding 0.3-0.4 µM of verteporfin.
Cebola teaches a composition comprising pancreatic multipotent progenitor cells (MPCs) contacted with 10 µM verteporfin (VP), wherein the pancreatic multipotent progenitor cells are PDX1+ and NKX6.1+ (2nd page of the Methods, right column, paragraph starting “VP experiments in….”; p616, left column, paragraph starting “To study the genomic…”), reading in-part on claim 34. Cebola further teaches the MPCs are NGN3+ (Fig. 6d, “NGN3”). In a separate embodiment, Cebola teaches contacting E11.5 mouse embryonic pancreatic bud explants with 0.1 µM verteporfin (2nd page of the Methods, right column, paragraph starting “Pancreatic explant experiments…”), reading in-part on claim 34. Cebola teaches that verteporfin treatment of human in vitro MPCs and pancreatic bud explants dissected from E11.5 mouse embryos and grown ex vivo caused decreased expression of a subset of genes associated with TEAD1-bound enhancers (p622, left column, paragraph starting “To study YAP-dependent TEAD function…”), reading in-part on claim 34.
Regarding the verteporfin concentrations of claim 34, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature 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). Also see M.P.E.P. § 2144.05 (II) and (III). In the instant case, Cebola teaches that the verteporfin concentration is a result effective variable to decrease expression of a subset of genes associated with TEAD1-bound enhancers in either pancreatic multipotent progenitor cells or in mouse embryonic pancreatic buds. Thus, the burden is shifted back to establish criticality of the claimed verteporfin concentration range by objective evidence.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Response to Arguments
Applicant's arguments on pages 5-8 of the reply have been fully considered, but not found persuasive of error for the reasons given below.
On pages 5-6 of the reply, Applicant appears to allege that the claimed composition is patent eligible under 35 U.S.C. § 101 by possessing markedly different characteristics. See M.P.E.P. § 2106.04(c). Applicant’s arguments are not persuasive because they are not reasonably commensurate to the scope of the claims. Applicant is claiming a composition of matter which is under consideration on the merits and not the disclosed methods of differentiating generic stem cells into pancreatic beta cells, and any alleged improvement in the number of beta cells generated by the disclosed method is not correlated to any particular markedly different characteristic in the claimed cells themselves.
Applicant’s remaining arguments on pages 6-8 of the reply are not found persuasive of error over the new grounds of rejection set forth above necessitated by the instant claim amendments.
Conclusion
No claims are allowed. No claims are free of the art.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
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/Sean C. Barron/Primary Examiner, Art Unit 1653