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
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 22 May 2026 has been entered.
Claim Status
In the reply filed on 22 May 2026, claim 14 is amended, claims 5, 10, 21, 23 and 25-28 were previously canceled.
Therefore, claims 1-4, 6-9, 11-20, 22, 24 and 29-31 are currently under consideration.
Priority
This application was filed 01/20/2023 and is a 371 application of PCT/NL2021/050474 filed on 07/23/2021, claims, filed 07/23/2020, which claims benefit to the foreign application 2026121 filed on 07/23/2020. Thus, the earliest possible priority for the instant application is 07/23/2020.
Withdrawn Rejections
The Applicant has amended the claim 14 to expressly identify the particular culture media being compared and recites that "the culture medium for proliferation of the pluripotent stem cells of step b )" and "the further culture medium for proliferation of the pluripotent stem cells of step f), when present," have the same or different compositions, and/or that "the culture medium for inducing differentiation of the cells towards the preselected cell type of step g)" and "any subsequent culture medium introduced upon repetition of steps g)-i)" have the same or different compositions. Therefore, breadth of amended claim 14 renders the prior claim rejection and accordingly, the prior rejection of Claim 14 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is hereby withdrawn.
Regarding 35 U.S.C. 103 rejection, Examiner argues that in the cited art Timmins differentiation (¶ [0170]) expressly recites that "All medium exchange steps were performed manually." Timmins does not disclose that these manual medium exchange steps were performed in a closed manner or without breaching the integrity of the culture system. Timmins disclosure, therefore, does not teach the claimed closed-culture medium-exchange sequence. Timmins ¶ [0012], [0037], [0042], and [0050] are generic statements that Timmins' dissociation method "may be carried out in a closed system"; they do not disclose a closed-system manufacturing process having the within-vessel media-exchange sequence of steps (c) - (j). Timmins therefore fails to disclose the preamble. Applicant’s arguments on preamble with respect to Timmins have been fully considered and are found persuasive (MPEP 2111.02). Accordingly, the prior rejection of claims 1-4, 6-9, 11-13, 15-20, 22, 24 and 29-31 in modified form under 35 U.S.C. 103 as being unpatentable over Timmins et al., (US20190031990A1), in view of Burridge et al., (PloS one, 6(4), p.e18293, 2011), further in view of Arauchi et al. (Frontiers in Endocrinology, 8, p.103, 2017) is hereby withdrawn.
Claim Rejections - 35 USC § 112(a)
Written Description
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4, 6-9, 11-20, 22, 24 and 29-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
As per MPEP 2163(I), "[T]he ‘essential goal’ of the description of the invention requirement is to clearly convey the information that an applicant has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Also, as per MPEP 2163.03(V), there is a presumption that an adequate written description of the claimed invention is present in the specification as filed.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Possession may be shown in a variety of ways, for example, possession may be shown by describing an actual reduction to practice of the claimed invention. A specification may describe an actual reduction to practice by showing that the inventor constructed an embodiment or performed a process that met all the limitations of the claim and determined that the invention would work for its intended purpose. Cooper v. Goldfarb, 154 F.3d 1321, 1327, 47 USPQ2d 1896, 1901 (Fed. Cir. 1998). See also UMC Elecs. Co. v. United States, 816 F.2d 647, 652, 2 USPQ2d 1465, 1468 (Fed. Cir. 1987) ("[T]here cannot be a reduction to practice of the invention ... without a physical embodiment which includes all limitations of the claim."); Estee Lauder Inc. v. L’Oreal, S.A., 129 F.3d 588, 593, 44 USPQ2d 1610, 1614 (Fed. Cir. 1997) ("[A] reduction to practice does not occur until the inventor has determined that the invention will work for its intended purpose."); Mahurkar v. C.R. Bard, Inc., 79 F.3d 1572, 1578, 38 USPQ2d 1288, 1291 (Fed. Cir. 1996) (determining that the invention will work for its intended purpose may require testing depending on the character of the invention and the problem it solves). Alternatively, applicant may present that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it").
Finally, MPEP 2163.04 describes the burden on the examiner with regard to the Written Description requirement, stating that in rejecting a claim, the examiner must set forth express findings of fact which support the lack of written description conclusion. These findings should:
(A) Identify the claim limitation(s) at issue; and
(B) Establish a prima facie case by providing reasons why a person skilled in the art at the time the application was filed would not have recognized that the inventor was in possession of the invention as claimed in view of the disclosure of the application as filed.
Claim 1 generally recites method for the in vitro manufacture of a preselected cell type differentiated from a pluripotent stem cell in a closed culture system, wherein the method comprises providing pluripotent stem cells and a genus of culture medium. The broadest reasonable interpretation of this claim includes not only any culture medium but also making for inducing differentiation of the pluripotent stem cells towards a genus of preselected cell. Claims 16 and 31 recite the genus of preselected cell type. Claims 20 and 31 recite the preselected cell type comprises the genus of compounds that induce differentiation of the pluripotent stem cells.
Instant specification discloses that the iPSCs were inoculated in the bioreactor (Dasbox Eppendorf) at a density of 40,000/mL in 250 ml StemMACS™ iPS-Brew XF (Miltenyi) containing 10 μM Y-27632 to promote aggregate formation, pH was controlled using NaHCO3 in the range of pH 7.2 and 7.4. The stirring speed was 200 rpm (DO 15%, 37° C.). After 72 hours (day 0) the biomass (aggregates with a typical size of 50-70 μm) was let settled for one hour. Conditioned medium (200 mL) was pumped into the collection bottle/bag. ‘EDM’ was prepared by mixing 0.25% albumin, 1% chemically defined lipid concentrate (Gibco) 0.5% pen/strep (gibco), 0.001% Trace-elements B, 0.01% Trace-elements C, 2 mM GlutaMAX, 0.05 mg/ml ascorbic acid (Sigma-Aldrich), 450 microM alpha-monothioglycerol (Sigma-aldrich) in IMDM/F12 media (Gibco). Differentiation was induced by adding 200 mL EDM containing 10 μM CHIR99021 (Axon Medchem)+31.25 ng/mL BMP4 (R&D Systems) to the bioreactor. After 120 h of differentiation, aggregates were allowed to settle and 200 mL of Conditioned medium (200 mL) was pumped into the collection bottle/bag and 200 mL of EDM containing 62.5 ng/mL VEGF and 12.5 μM SB431542 (Tocris) was added ([0229]-[0232] of US20230295570A1). Therefore, the specification fails to identify the broadest reasonable interpretation of this method claim includes manufacturing of any preselected cell type differentiated from a pluripotent stem cells (PSCs) in a closed culture system using any culture medium includes any compounds that induce differentiation of the PSCs.
The disclosure as originally filed shows a clear reduction to practice of the invention (e.g., as per the Examples and Figures) for specific compound was induced (mTeSR1, BMP4, VEGF, SCF) was added to the bioreactor [0238] for the differentiation to specific cell type such as Cardiomyocyte [0222], Endothelial Aggregates [0229] Single Cell Monocytes [0236], Cortical Neurons [0249] and hemogenic endothelium ([0261] of US20230295570A1). Therefore, it is apparent that Applicant was in possession of manufacturing of specific preselected cell type differentiated from a pluripotent stem cells (PSCs) in a closed culture system using specific culture medium includes specific compounds that induce differentiation of the PSCs as of the effective filing date.
However, as detailed in MPEP § 2163, besides an actual reduction to practice, Applicant may prove possession of the claimed invention by a showing that the invention was “ready for patenting” such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the Applicant was in possession of the claimed invention. Further, as per MPEP § 2163, “[f]or some arts, there is an inverse correlation between the level of skill and knowledge in the art and the specificity of disclosure necessary to satisfy the written description requirement.”
In the prior art, Kempf et al., (Nature Protocols, 10(9), 2015, pp. 1345-1361; cited in IDS filed 01/20/2023; hereinafter “Kempf”) teaches a method for the in vitro manufacture of a preselected cell type (i.e., Cardiomyocytes (CMs)) differentiated from a pluripotent stem cell (abstract, Fig. 1), preferably in a closed culture system (Fig. 5a), wherein the method comprises the steps of: providing pluripotent stem cells and a culture medium (step 16(B)(ii) of Kempf); introducing the pluripotent stem cells and the culture medium (i.e., RPMI 1640 for differentiated cells) into a culture vessel (step 16(B)(iv), figure 5a of Kempf), wherein the proliferation of the pluripotent stem cells (mTeSR1 with Y27632 is a culture medium for proliferation (step 16(B)(ii) of Kempf); or a culture medium for inducing differentiation of the pluripotent stem cells (mTeSR1 with CHIR99021 is a culture medium for differentiation (step 16(B)(xv) of Kempf) towards the preselected cell type. Therefore, it is obvious that prior art does not support to identify the generic manufacturing of any preselected cell type differentiated from a pluripotent stem cells (PSCs) in a closed culture system using any culture medium includes any compounds that induce differentiation of the PSCs.
Accordingly, it concludes that the claimed genus of any preselected cell type differentiated from a pluripotent stem cells (PSCs) in a closed culture system using any culture medium includes any compounds that induce differentiation of the PSCs doesn't have an adequate written description. It concludes that a skilled artisan would find the specification inadequately described. Therefore, the Applicant did not sufficiently possess the broader invention as claimed in claim 1 and dependent claims 2-4, 6-9, 11-20, 22, 24 and 29-31.
Response to Arguments
Applicant's arguments filed on 22 May 2026 are acknowledged.
The rejection under 103 over Timmins has been withdrawn in view of the Applicant’s arguments on preamble have been fully considered and are found persuasive (MPEP 2111.02). Applicant’s arguments are moot.
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).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached on (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
Prosecution Insights