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 8/12/2026 to claims 1 and 3-10 have been entered. Claims 2 and 11-24 are canceled. Claims 1 and 3-10 remain pending and are being considered on their merits. No claims are withdrawn from consideration at this time. References not included with this Office action can be found in a prior action. The instant amendments to claim 1 have overcome the 35 U.S.C. § 102 rejections of record over Dormady, which are withdrawn. The instant amendments to claims 1 and 7 have overcome the 35 U.S.C. § 112(b) rejections of record over Dormady, which are withdrawn.
Any rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments.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 § 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 1, 3, 4, 8, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Dormady et al. (PNAS (2000), 97(22), 12260-12265; provided in the IDS dated 1/17/2025) in view of Broxmeyer et al. (Blood (2011), 117(18): 4773-4777; of record).
Dormady teaches an in vitro method of expanding murine bone marrow cells (BMCs) to form hematopoietic colonies (e.g. hematopoietic stem and progenitor cells derived from bone marrow), the method comprising contacting the cells with recombinant and full-length GAS6 at 100 ng/ml (the paragraph spanning pages 12263-12264, and noting the lack of any feeder cells), reading in-part on claims 1, 3, and 9.
Regarding claim 1, Dormady does not teach human hematopoietic stem and progenitor cells (HSPCs). Alternatively regarding claim 3, Dormady does not teach HSPCs obtained from cord blood. Regarding claim 8, Dormady does not teach CD34+ HSPCs.
Broxmeyer teaches human hematopoietic stem and progenitor cells obtained from cord blood and after long-term frozen storage (HPCs and HSCs), and wherein the HSCs are CD34+ (pages 4774-4775, subheadings “HPC recovery” and “HSC activity”; also page 4773, 1st paragraph of the methods for human cord blood cells citing Reference 2), reading on claims 2 and 8. Broxmeyer teaches that cryopreservation of hematopoietic stem cells and hematopoietic progenitor cells is crucial for cord blood banking and transplantation (Abstract), reading on claims 2 and 8.
Regarding claims 1 and 8 and alternatively regarding claim 3, it would have been obvious to a person of ordinary skill in the art before the invention was filed to substitute the unspecified (but likely murine) source of HSPCs of Dormady with the human CD34+ HSPCs obtained from cord blood of Broxmeyer. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Dormady and Broxmeyer are in-part directed towards methods of obtaining and culturing HSPCs. The skilled artisan would have been motivated to do so because Broxmeyer teaches that human CD34+ HSPCs would be advantageous in downstream methods of HSPC transplantation to (human) subjects in need thereof, and so the substitution would predictably improve upon the methods of Dormady to generate HSPCs for further transplantation into (human) subjects.
Regarding claim 4, this claim recites a wherein clause directed towards improved expansion of human HSPCs when contacted with a GAS6 polypeptide, a variant or fragment thereof, which has been fully considered but is not given any patentable weight as it is only directed towards the intended outcome of claim 1. Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. See M.P.E.P. § 2111.04. As such, the methods of Dormady are reasonably presumed capable of meeting the wherein clause of claim 4 in the absence of any showing to the contrary (see M.P.E.P. § 2112).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 5-8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Dormady and Broxmeyer as applied to claim 1 above, and further in view of Manesia et al. (Blood (2019), 134(Supplement_1): 1185; provided in the IDS dated 1/17/2025).
The teachings of Dormady and Broxmeyer are relied upon as set forth above.
Regarding claims 5 and 10, Dormady does not teach further comprising contacting the HSPCs with a stem cell agonist cocktail comprising StemReginin1 (SR1), UM171, L-ascorbic acid 2-phosphate magnesium salt hydrate (AA2P) and/or valproic acid (VPA) (i.e. the stem cell agonist cocktail). Regarding claim 6, Dormady does not teach wherein the normal HSPCs are contacted with the stem cell agonist cocktail prior to contacting the GAS6 polypeptide. Regarding claim 7, Dormady does not teach a) about 100 nM to about 5025 nM of StemReginin1; b) about 0.10 nM to about 150 nM of UM171; c) about 0.1 µM to about 2 000 µM of AA2P; and/or d) about 0.01 mM to about 1 mM of valproic acid. Alternatively regarding claim 8, Dormady does not teach CD34+CD45RA- HSPCs and higher cell surface expression of EPCR.
Manesia teaches a method of expanding hematopoietic stem cells obtained from (human) cord blood and being CD34+CD45RA- and having high expression of EPCR, by contacting said cells with a stem cell agonist cocktail comprising StemReginin1 (SR1), UM171, L-ascorbic acid 2-phosphate magnesium salt hydrate (AA2P) and/or valproic acid (VPA) (Introduction and Methods on the 1st and 2nd page, Table 1 on the 3rd page noting relative concentrations of each compound), alternatively reading on claim 3, reading on claims 5, 6, 8 and 10 and reading in-part on claim 7. Manesia teaches that loss of self-renewal of hematopoietic stem cells (HSC) is a major roadblock to cell engineering therapies (Introduction on the 1st page), reading on claims 5-7 and 10 and alternatively reading on claims 3 and 8.
Regarding claims 5, 6, and 10, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further contact the HSPCs of Dormady with the stem cell agonist cocktail of Manesia. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Dormady and Manesia are in-part directed towards methods of obtaining and culturing HSPCs. The skilled artisan would have been motivated to do so because Manesia teaches that that loss of self-renewal of hematopoietic stem cells (HSC) is a major roadblock to cell engineering therapies, and so the addition would predictably improve upon the methods of Dormady to expand HSPCs for further cell engineering therapies.
Regarding claim 7, optimization within prior art conditions or through routine experimentation will generally not support patentability absent a showing of criticality of the claimed range to the contrary. See M.P.E.P. § 2144.05, particularly subsections II and III. In this case, while Dormady does not teach any of the claimed concentration ranges, Dormady teaches relative concentrations of StemReginin1 (SR1), UM171, L-ascorbic acid 2-phosphate magnesium salt hydrate (AA2P) and valproic acid (VPA) are effective to culture and expand HSPCs. Thus, the burden is shifted back to establish criticality of the claimed concentration ranges by objective evidence.
Alternatively regarding claim 8, it would have been obvious to a person of ordinary skill in the art before the invention was filed to substitute the HSPCs of Dormady with the CD34+CD45RA-EPCRhigh HSPCs obtained from (human) cord blood of Manesia. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Dormady and Manesia are in-part directed towards methods of obtaining and culturing HSPCs. The skilled artisan would have been motivated to do so because Manesia teaches that the CD34+CD45RA-EPCRhigh HSPCs obtained from cord blood would be advantageous in downstream methods of cell engineering therapies, and so the substitution would predictably improve upon the methods of Dormady to generate HSPCs for further transplantation into subjects in need of treatment thereof.
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 4-5 of the reply have been fully considered, but not found persuasive of error for the reasons given below.
On pages 4 of the reply, Applicant alleges that Dormady is inoperable in so much that the subheading on pages 12263-64 is entitled “Soluble GAS6 Does Not Support Hematopoiesis”. This is not persuasive as Dormady teaches “There was no difference between the number of colonies formed by cells plated without GAS6 and cells plated in 100 ng/ml GAS6 (93.3 ± 4.5 vs. 92.3 ± 3.6).” and so the GAS6-treated HSPCs expand to the same degree as the non-GAS6-treated HSPCs, thus reading in-part on claim 1. The broadest reasonable interpretation (see M.P.E.P. § 2111) of the generic “expanding” as set forth in claim 1 does not require any particular degree of expansion (e.g. cell number, or cell number over a time range) nor any particular degree of expansion caused by GAS6 treatment of HSPCs relative to non-GAS6 treated HSPCs that might otherwise prompt reconsideration over Dormady at this time, and so Applicant’s arguments are not reasonably commensurate to the scope of the claim.
Applicant’s arguments on page 5 of the reply are not persuasive of error for several reasons. In order, 1) Dormady teaches that the long term bone marrow cultures (LTBMCs) were “minimally hematopoietic” and “By day 24, stromal monolayers with obvious hematopoiesis had developed in all cultures, but the monolayers in the GAS6 -supplemented cultures had fewer hematopoietic foci” thus meeting the broadest reasonable interpretation of claim 1 and providing for a reasonable expectation of success. Again, claim 1 was not amended to require any particular degree of expansion over any particular time range that might prompt reconsideration over Dormady at this time. Arguments presented by the applicant cannot take the place of evidence in the record, and statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding the alleged inoperability of the prior art; see M.P.E.P. § 716.01(c)(I) and (II), and Applicant furnished no such Affidavit or Declaration with the instant reply. 2) Applicant continues to allege error over unclaimed features, as claim 1 does not exclude the animal-derived serum of Dormady because the “comprising” translation phrase permits additional, unrecited elements (see M.P.E.P. § 2111.03(I)); although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
At this time, Dormady only differs from claim 1 by teaching murine HSPCs and which is fully addressed by the inclusion of Broxmeyer in the obviousness rejection above and necessitated by the instant amendments.
Applicants remaining arguments on page 5 of the reply rely on arguments traversing the above rejection of claim 1 over Dormady and Broxmeyer to traverse the rejection of claims 5-8 and 10 further in view of Manesia. Therefore, the response set forth above to arguments also applies to this rejection.
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
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