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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/04/2026 has been entered.
Claim Status
The amendment of 03/04/2026 has been entered. Claims 1-3 and 5-15 are pending in this US patent application. Claims 5-8 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 01/16/2024.
Claims 1-3 and 9-15 are currently under examination and were examined on their merits.
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.
Claims 1-3 and 9-15 are rejected under 35 U.S.C. 103 as being unpatentable over Nath et al., Bioprocess Biosyst. Eng. 40: 123-231 (2017; published online 09/16/2016).
Nath teaches a method to refine the culture medium of human induced pluripotent stem cells (hiPSCs) by dialysis (see entire document, including page 124, left column, paragraph 2; cf. claims 2, 10, and 13). The dialysis of the culture medium is important because hiPSCs produce toxic metabolites during culture, including lactic acid and ammonium, that reduce the growth of hiPSCs in suspension culture (page 123, right column, paragraph 2; the Examiner notes that ammonium ion is ammonia that has been dissolved in water). The hiPSCs were cultured in a medium refining system with a dialysis membrane filter by which used suspension culture medium was refreshed with DMEM/F-12 as the dialysate. To analyze metabolites and cytokines, medium was sampled before and after dialysis (page 124, right column, paragraph 2; cf. claims 1, 9, and 12 [“…repeatedly detecting…adding, with or without discarding the culture solution housed in a culture vessel together with the cell, the culture solution”]; the Examiner notes that the dialysis method taught by Nash requires the periodic addition of fresh medium to the culture bioreactor). Prior to dialysis, the concentrations of lactic acid and ammonium in the culture medium were 1.18 g/L and 0.01 g/L, respectively, and these compounds could not be detected in the culture medium following dialysis (page 126, Table 1; cf. claims 1, 3, 9, 11-12, and 14-15; the concentrations of lactic acid and ammonium prior to dialysis convert to 13 mM and 0.55 mM, respectively; the inability to detect lactic acid and ammonium in the culture medium following dialysis indicates that the concentrations of these metabolites following dialysis intrinsically satisfy conditions (I) and (II) in claims 1, 3, 9, 11-12, and 14-15; the Examiner notes that the undetectable concentrations of lactic acid and ammonium following dialysis indicate that the process for removing these compounds was stopped when the concentrations were lower than the concentrations recited in the instant claims). The concentration at which ammonium was removed from the culture medium was a trace amount that did not exceed the minimum inhibitory level (page 128, right column, paragraph 2). The cells retained expression of pluripotency markers (page 128, right column, paragraph 3; cf. claims 1 and 9).
However, while the lactic acid concentration in the culture medium of Nath prior to dialysis falls within the range recited in claims 1, 9, and 12 (“…7.5 mM or higher”), Nath does not teach that dialysis was initiated at the specific ammonium concentration recited in instant claims 1, 9, and 12.
While Nath does not teach that dialysis was initiated at the specific ammonium concentration recited in instant claims 1, 9, and 12, it would have been obvious to one of ordinary skill in the art to initiate the removal of ammonium from the culture medium of Nath at any concentration of ammonium because Nath indicates that ammonium is a toxic metabolite that decreases iPSC growth, as discussed above. In addition, Nath indicates that the removal of ammonium occurred at an ammonium concentration that was below the minimum inhibitory concentration of the metabolite in iPSC culture medium. One of ordinary skill in the art would have a reasonable expectation that removing ammonium from iPSC culture medium at any ammonium concentration, including those recited in instant claims 1, 9, and 12, would successfully result in the removal of a toxic metabolite from the culture medium and an increase in iPSC proliferation.
Therefore, claims 1-3 and 9-15 are rendered obvious by Nath and are rejected under 35 U.S.C. 103.
The Supreme Court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation…103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions……the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) (emphasis added).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant has traversed the above rejection of the claims under 35 U.S.C. 103 as being unpatentable over Nath. Applicant states that the amended claims recite limitations not found in Nath (remarks, pages 6-7). These remarks have been fully considered but have not been found persuasive.
The Examiner notes that Nath teaches or renders obvious all of the limitations recited in the instant claims, as discussed above. As such, the Examiner does not concur with Applicant’s assertion that the amended claims recite limitations not found in Nath.
Therefore, the Examiner has maintained the rejections presented above.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Erin M. Bowers, whose telephone number is (571)272-2897. The examiner can normally be reached Monday-Friday, 7:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau, can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Erin M. Bowers/Primary Examiner, Art Unit 1653 03/11/2026