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 .
DETAILED ACTION
This action is in response to the papers filed on June 17, 2026. Pursuant to
amendment filed June 17, 2026, claims 1, 8-9, 11-12, and 15-16 are amended. Claims 2, 4-6, 10, and 13-14 have been canceled. Claims 1, 8, 11, and 12 are independent claims.
Election/Restrictions
Applicant's election with traverse of Group II, drawn to a culture medium composition, comprising human cells and polyalkylene glycol modified with a copolymer containing a polyvinylcaprolactam block and a polyvinylacetate block, in the reply filed on June 17, 2026, is acknowledged. As amended, pending claims 11, 12, 15 and 16 correspond to the elected composition invention. Applicant also canceled claims 2, 10, 13, and 14, and added claims 15 and 16, which are drawn to the elected Group II invention.
The traversal is on the grounds that the amended claims have unity of invention because the claims share a culture medium comprising polyalkylene glycol modified with a copolymer containing a polyvinylcaprolactam block and a polyvinylacetate block, together with one of the combinations recited as elements (1)-(3), and that neither Guth nor Sauvageau discloses or suggests the claimed combination. Applicant further argues that Guth does not describe or suggest culturing human hematopoietic stem cells or human blood cells and that Sauvageau does not describe or suggest the claimed modified polyalkylene glycol copolymer.
This argument is not found persuasive because the ordinary artisan would have recognized that the cited prior art collectively teaches the claimed common technical features and their established use in cell culture systems, including hematopoietic cell culture systems. Specifically, Guth teaches an amphiphilic N-vinyl caprolactam and vinyl acetate moieties grafted on a polyethylene glycol backbone, or a PEG-PVAc-PVCap graft copolymer, as a cell culture reagent, wherein N-vinylcaprolactam and vinyl acetate moieties are grafted onto a polyethylene glycol backbone (Abstract; [0001]; [0017-0029]; [0054]; [0060]; claim 1). Guth teaches cell culture media comprising the PEG-PVAc-PVCap graft copolymers and teaches the commercially available graft copolymer Soluplus® as a preferred embodiment ([0029]; [0053-0066]). Guth further teaches that the polymer is useful as a stabilizing cell culture supplement and shear protectant and that cultures containing the PEG-PVAc-PVCap graft copolymer exhibit increased cell viability and growth rates ([0002-0010]; [0030]; [0054-0067]; [0108]).
Although Guth expressly teaches polyethylene glycol, rather than specifically describing the entire presently claimed polyalkylene glycol genus, polyethylene glycol is a species encompassed by the claimed polyalkylene glycol limitation. The instant specification identifies polyethylene glycol as an exemplary polyalkylene glycol and discloses embodiments wherein the modified polyalkylene glycol is polyethylene glycol modified with a copolymer containing a polyvinylcaprolactam block and a polyvinylacetate block ([0001]; [0008-0009]; [0025-0028]; [0044-0050]). Guth therefore teaches at least one species falling within the scope of the modified polyalkylene glycol genus relied upon by Applicant as common technical feature. The use of a broader generic terminology in the claims therefore does not, by itself, establish a special technical feature. Guth further teaches that its cell method is applicable to human or animal cell lines, including stem cells, cells derived from bone marrow, leukemias and lymphomas, and modified or antigen-activated T cells ([0033]; [0037]).
Likewise, Sauvageau teaches ex vivo expansion of human hematopoietic stem and progenitor cells and expressly employs serum-free HSC expansion media containing defined growth factors. Sauvageau teaches culturing human cord-blood-derived CD34+ or CD34+CD45RA- cells in HSC expansion medium comprising StemSpan SFEM supplemented with stem cell factor (SCF), FLT3 ligand, and thrombopoietin (TPO), together with the HSC expansion compound UM171 and other cell-expanding factors ([0003]; [0021-0023]; [0041-0077]; [0110]; Example 1). Sauvageau additionally teaches that cytokines and growth factors useful for HSC/HPC expansion include SCF and TPO and that biologically active analogs may be employed. In particular, Sauvageau expressly identifies cytokine receptor agonists, including an agonist antibody against the TPO receptor, as suitable analogs and teaches that cytokine and growth-factor combinations are selected to expand hematopoietic stem cells and progenitor cells while limiting terminal differentiation ([0105]). Additionally, Sauvageau’s teachings demonstrate that a standard combination of FLT3, SCF, and TPO and IL-6, is effective in stimulating expansion of EPCR+ cells from CD34+ cells exposed to UM171 ([0061]). Hence, Sauvageau teaches the use of a TPO receptor against together with SCF in a human hematopoietic stem cell culture system. This corresponds to the SCF of alternative (2) of amended independent claims 11 and 12 which recites “a TPO receptor agonist and at least one compound selected from the group consisting of stem cell factor (SCF) and PI3K activators.”
Thus, the ordinary artisan would have found it obvious, in view of the combined teachings of Guth and Sauvageau, to employ Guth’s PEG-PVAc-PVCap modified polyethylene glycol cell culture additive in the human hematopoietic stem cell culture media taught by Sauvageau, including media employing SCF together with TPO or a TPO receptor agonist. Guth teaches the modified polyethylene glycol copolymer as a known cell-culture stabilizing additive applicable to human and animal cell culture systems and demonstrates maintenance of cell viability and growth, while Sauvageau teaches defined culture conditions for expansion of human hematopoietic stem cell and progenitor cells employing SCF and TPO/TPO receptor signaling. The ordinary artisan therefore would have been motivated to combine the known cell-culture additive of Guth with the HSC expansion system of Sauvageau, with a reasonable expectation that the additive would perform its known cell-culture stabilizing function.
Therefore, the modified polyalkylene glycol and the recited growth-factor alternatives relied upon by Applicant do not constitute a special technical feature defining a contribution over the prior art. The requirement is still deemed proper and is therefore made FINAL. Claims 1, 3, and 7-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected groups of inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on June 17, 2026. The restriction requirement between Groups I-II is still deemed proper and made FINAL.
It is noted that when a final requirement for restriction is made by the examiner, applicant may file a petition under 37 CFR 1.144 for review of the restriction requirement. The propriety of a requirement to restrict, if traversed, is reviewable by petition under 37 CFR 1.144. In re Hengehold, 440 F.2d 1395, 169 USPQ 473 (CCPA 1971). Petition may be deferred until after final action on or allowance of claims to the invention elected, but must be filed not later than appeal. A petition will not be considered if reconsideration of the requirement was not requested (See § 1.181.).
Therefore, claims 11-12 and 15-16 are currently under examination.
Priority
The present application is a 35 U.S.C. 371 national stage filing of the International Application No. PCT/JP2021/002252, filed on January 22, 2021, which claims priority to Japanese Application No. 2020-010390, filed on January 24, 2020, is acknowledged.
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Japan on January 24, 2020. Filing on July 22, 2022, of certified untranslated copy of the Japanese publication 2020-010390 filed on July 22, 2022, is acknowledged. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CPR 41.154(b) and 41.202(e). Failure to provide a certified translation may result in no benefit being accorded for the non-English application. At present, applicant has asserted that “translation is not required at this time” and has still not provided the office with translation.
Thus, priority is not yet perfected and the earliest possible priority for the instant application is January 24, 2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 07/22/2022, 10/06/2023, 02/16/2024, 05/14/2024, and 08/01/2024 were filed. The submissions are in compliance with the provisions of 37 CPR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 15 should be amended to recite: “serum albumin-free composition,” consistent with the specification (instant specification [0006] and [0026]).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 11-12 and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Sauvageau et al. (US 20190085291 A1), in view of Guth et al. (citations to US 2021/0163879 A1; prior published June 27, 2019, WO 2019121053 A1).
Regarding claim 11, Sauvageau teaches ex vivo culture and expansion of human hematopoietic stem and progenitor cells. Sauvageau teaches culturing human cord-blood-derived CD34+ or CD34+CD45RA- cells in HSC expansion medium comprising StemSpan SFEM supplemented with stem cell factor (SCF), FLT3 ligand, and thrombopoietin (TPO), with the culture medium supplemented with UM171 or SR1 ([0108-0110]). Sauvageau further teaches that cytokines and growth factors generally known for HSC/HPC expansion include SCF, FLT3, TPO, and analogs thereof, and that combinations including FLT3, SCF, and TPO can be employed to expand the hematopoietic cells ([0061]; [0105]). Sauvageau teaches that the cytokine and growth-factor analogs include structural variants having the biological activity of the naturally occurring factors, including cytokine receptor agonists such as an agonist antibody against the TPO receptor, and teaches that cytokine and growth-factor combination are selected to expand HSC and progenitor cells while limiting production of terminally differentiated cells ([0105]). Thus, Sauvageau teaches the use of a TPO receptor agonist as an alternative to TPO in an HSC expansion medium containing SCF, corresponding alternative (2), a TPO receptor agonist together with SCF.
Sauvageau does not teach the recited polyalkylene glycol modified with a copolymer containing a polyvinylcaprolactam and a polyvinylacetate.
However, Guth teaches cell culture media comprising an amphiphilic PEG-PVAc-PVCap graft copolymer used as a stabilizing cell-culture reagent and shear protectant, including for human or animal cell culture ([0001]). Guth further teaches graft polymers comprising a hydrophilic polyethylene glycol backbone grafted with copolymer chains of N-vinylcaprolactam and vinyl acetate and identifies the preferred commercially available PEG-VCap-Vac graft polymer as Soluplus® ([0022-0029]). Polyethylene glycol is a species of the presently claimed polyalkylene glycol genus. Hence, Guth teaches a species encompassed by the modified polyalkylene glycol limitation of claim 11.
Guth additionally teaches that the use of the PEG-VCap-VAc graft polymer for human or animal cells cultures, including stem cells and cells derived from bone marrow, as well as modified or antigen-activated T cells ([0033-0037]). Guth also teaches that modified or enriched culture media may contain surfactants to improve cell-culture performance or maintained concentrated media in solution and specifically identifies PEF-PVAc-PVCap graft copolymer (Soluplus®) as a polymeric solubilizer suitable for providing such benefit ([0049]; [0053-0054]). Guth reports cultures containing PEG-PVAc- PVCap graft copolymer exhibited cumulative cell-growth rates and cell viability in the same range as cultures containing the standard shear protectant poloxamer 188 ([0060-0064]).
Therefore, before the effective filing date of the instant application, the ordinary artisan would have found it obvious to modify the human HSC expansion medium of Sauvageau by including the PEG-PVAc-PVCap modified polyethylene glycol cell culture additive taught by Guth. One of ordinary skill would have been motivated to make such a modification because Guth expressly teaches the polymer as a cell-culture stabilizing additive applicable to human and animal cell culture systems and teaches that such additive provides cell-culture performance, growth, viability, and stabilization benefits ([0001]; [0033-0034]; [0053-0054]; [0060-0064]). One of ordinary skill would therefore have reasonably expected Guth’s known cell-culture additive to perform its known stabilizing and cell culture supporting function when incorporated into Sauvageau’s HSC expansion medium. Sauvageau teaches that the cultured HSC/HPC populations are maintained and expanded using combinations of known cytokines and growth factors, including SCF and TPO/TPO analogs ([0061]; [0105]; [0110]).
Regarding independent claim 12, Sauvageau further teaches compositions comprising human hematopoietic stem/progenitor cells in the disclosed HSC expansion medium. Specifically, Sauvageau teaches culturing human cord blood derived CD34+ or CD34+CD45RA- cells in HSC expansion medium comprising StemSpan SFEM supplemented with SCF, FLT3 ligand, and TPO, and further teaches supplementation with UM171, SR1, or vehicle ([0108-0110]). Therefore, upon modifying Sauvageau’s HSC culture medium to include the PEG-PVAc-PVCap modified polyethylene glycol taught by Guth, for the same reasons set forth above, with respect to claim 11, the resulting composition would comprise the human hematopoietic cells, modified polyethylene glycol, and the recited growth factor combination.
Regarding claim 15, the combined teachings of Sauvageau and Guth render claim 11 obvious. Additionally, Guth further teaches that chemically defined culture media are preferred because they provide better traceability and lot-to-lot consistency, and teaches that improvements in chemically defined media seek to avoid complex components of unknown composition and to eliminate animal-derived components ([0046-0047]). Thus, the ordinary artisan would have found it obvious to provide the culture medium of Sauvageau, as modified Guth, in a serum albumin-free form in order to eliminate an animal-derived component and thereby obtained improved traceability, lot-to-lot consistency, process-development, and regulatory advantages associated with chemically defined media, as taught by Guth.
Regarding claim 16, the combined teachings of Sauvageau and Guth render claim 11 obvious. Guth additionally teaches that the graft copolymer comprises a hydrophilic polyethylene glycol backbone grafted with copolymer chains of N-vinylcaprolactam and vinyl acetate. Guth further teaches a particularly preferred graft polymer comprising PEG 6000, N-vinylcaprolactam, and vinyl acetate, commercially available as Soluplus ([0022-0029]). Guth therefore expressly teaches the polyethylene glycol species additionally required. Thus, the ordinary artisan would have found it obvious to use polyethylene glycol as the polyalkylene glycol of the modified culture medium because Guth expressly teaches polyethylene glycol as the backbone of its PEG-PVAc-PVCap graft copolymer and identifies the PEG 600-containing graft polymer as a preferred embodiment.
Conclusion
Claims 11-12 and 15-16 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOEL D LEVIN whose telephone number is (571)270-0616. The examiner be reached 8:00 am to 5:00 pm, Monday through Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.D.L./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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