DETAILED ACTION
Applicant’s amendment and response received on 7/13/26 has been entered. Claim 24 has been canceled. Claims 23 and 25-37 are currently pending and under examination in the instant application. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . An action on the merits follows.
Those sections of Title 35, US code, not included in this action can be found in a previous office action.
Information Disclosure Statement
The two information disclosure statements (IDS) submitted on 7/13/26 are in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the information disclosure statements have been considered by the examiner and initialed and signed copies of the 1449s are attached to this action.
Claim Rejections - 35 USC § 112
The rejection of Claim 24 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, is withdrawn in view of applicant’s cancellation of this claim.
Applicant’s amendments to the claims has necessitated the following new grounds of rejection.
Claims 23 and 25-37 are newly rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Independent claim 23 has been amended to recite as a preamble, “[a] method of generating induced pluripotent stem cell (iPSC) lines from immortalized lymphoblastoid cell lines in feeder-free conditions, for each iPSC line from each immortalized lymphoblastoid cell line, the method comprises”, and further at the end of the claim to recite, “wherein the method of generating iPSC lines from the immortalized lymphoblastoid cell lines is 100% reproducible”. Both of these added limitations is confusing. In regards to the preamble, the recitation, “for each iPSC line from each immortalized lymphoblastoid cell line” is confusing as it is unclear whether applicant intends that more than one immortalized lymphoblastoid cell line is present and that “each” undergoes the same method steps at the same time such that each immortalized lymphoblastoid cell line present in the mixture produces its own iPSC line, or whether applicant simply intends that this method produces one iPSC line from one immortalized lymphoblastoid cell line, particularly as the first step of the method recites “providing lymphoblastoid cells from an immortalized lymphoblastoid cell line”, where “an immortalized lymphoblastoid cell line” is singular not plural and thus does not appear to include multiple immortalized lymphoblastoid cell lines. Thus, the reference to “each PSC line from “each immortalized lymphoblastoid cell line” is indefinite as the metes and bounds of this recitation within the context of the method steps cannot be determined.
Further, the new limitation at the end of claim 23 which recites, “wherein the method of generating iPSC lines from the immortalized lymphoblastoid cell lines is 100% reproducible” is further confusing since again it is unclear whether more than one immortalized lymphoblastoid cell line is used in the instant method steps. In addition, it is unclear what is meant by the method being “100% reproducible”. The specification does not teach that the method is “100% reproducible”. The specification states that the method is “highly reproducible” or that the method is “highly efficient, reproducible” (specification page 8). Applicant does not state where support for this newly added limitation may be found in the specification. It is noted that page 29 of the specification states that “reprogramming success was very reliable at 100%” pointing to Table 1, where reprogramming of 14 different lymphoblastoid cell lines into iPSC lines resulted in reprogramming efficiency of greater than 0, more specifically between 0.001% and 0.06% reprogramming efficiency, for each starting lymphoblastoid cell line, which reprogramming efficiency measures how many of the original lymphoblastoid cells of an LCL subjected to the reprogramming method generate an iPSC. However, it is unclear whether “100% reliability” is the same “100% reproducible”. There is no particular definition of either of these terms. As such, it is unclear whether reproducibility requires achieving the same results, i.e. the same reprogramming efficiency, or whether reproducibility is intended to suggest that each time the same lymphoblastoid cell line is reprogrammed that it is reprogrammed at the same efficiency, or whether reproducibility is intended to mean that at least one cell for each parent LCL subjected to applicant’s method is reprogrammed to an iPSC in each practice of the method. As such, the metes and bounds of the claim cannot be determined. Claims 25-37 depend on claim 23 and thus are included in this rejection.
In the interests of compact prosecution, it is noted that the limitation “wherein the method of generating iPSC lines from the immortalized lymphoblastoid cell lines is 100% reproducible” has been given its broadest reasonable interpretation as encompassing the reliable generation of at least one iPSC line from a single immortalized lymphoblastoid from each practice of the method.
Claim Rejections - 35 USC § 103
The rejection of claims 23-32, and 36-37 under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication 2012/0009676 (January 12, 2012), hereafter referred to as Mack, in view of Hong et al. (2009) Nature, Vol. 460(7259), 1132-1135, Rajesh et al. (2011) Blood, Vol. 118(7), 1797-1800, U.S. Patent Application Publication 2016/0145642 (2016), hereafter referred to as Cui et al., with an effective filing date of 7/12/13, and U.S. Patent Application Publication 2012/0196360 (August 2, 2012), hereafter referred to as Okita et al., is withdrawn over canceled claim 24, withdrawn over canceled claims 23, and 25-32, and maintained over claims 36-37. Applicant’s amendments to the claims, arguments and the Declaration under 37 CFR 1.132 by Dhruv Sareen (the Sareen Declaration), attached as Exhibit 1, have been found persuasive in regards to the method claims, claims 23, and 25-32, but have not been found persuasive in overcoming the rejection over the product by process claims, claims 36-37.
The applicant argues that independent claim 23 has been amended to recite that the method produces iPSC cell lines from immortalized LCLs with “100% reproducibility”, and that the Sareen Declaration states that Mack et al. teaches that their methods are only effective on CD34+ cells, whereas lymphoblastoid cells are CD34-, and that attempts to use the Rajesh method, or another method disclosed by Choi et al. in the prior art, to generate iPSCs from lymphoblastoid cell lines were unsuccessful in the hands of the Declarant in reliably generating iPSCs. According to the Declaration, the reprogramming efficiency of the Mack method using CD34- cells was zero, and that even with the knowledge provided by the secondary references that silencing p53 may be helpful, it would have been unpredictable whether the addition of an siRNA to silence p53 in combination with Mack’s method would result in the successful generation of iPSCs from LCLs. The applicant further argues that even if one skilled would have reasonable believed that an iPSC line could be produced from immortalized LCLs based on the combination of cited references, there would have been no reasonable expectation of 100% reproducibility using the claimed methods. According to applicant, the 100% reproducibility is a greater than expected result (unexpected result).
In response, despite issues of indefiniteness as to the metes and bounds of the phrase “100% reproducible” as discussed in the rejection of the claims for indefiniteness under 35 U.S.C. 112(b) above, the added limitation does carry weight in terms of at least the reliability of the method, which as set forth in Table 1 demonstrated the generation of an iPSC from each of 14 different LCLs subjected to the method as claimed. As such, applicant’s arguments and the Sareen Declaration has been found persuasive in terms of the reliability/reproducibility of the method claims.
However, claims 36-37 are product by process claims. “Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted). In this case, the % reliability/reproducibility of the method used to generate the iPSC does not change the structure of the iPSC line generated. Thus, even the demonstration or expectation of generating at least one iPSC from an immortalized lymphoblastoid cell line would be enough to render obvious the product which is an iPSC. Turning to the rejection of record, Rajesh et al. in particular provides specific evidence that LCLs as claimed can be reprogrammed using a technique similar to that disclosed by Mack et al. While the Sareen Declaration states that they were not able to reliably generate iPSCs using the Rajesh methodology, it is noted that the Sareen Declaration does not state that they were unable to reproduce the same results obtained by Rajesh et al., but rather that the method was not “reliable”, suggesting perhaps that it worked some times, and not other times. In addition, the rejection of record further cited Hong et al. for teaching that the formation of iPS cells from terminally differentiated somatic cells expressing reprogramming factors is suppressed by p53 expression and that inhibition of p53 expression enhances iPS generation from somatic cells including terminally differentiated lymphocytes (Hong et al., pages 1132-133). Hong et al. teaches that p53 can be effectively inhibited by introduction of a vector comprising a nucleic acid encoding shRNA-p53 and that the introduction of nucleic acids encoding four reprogramming factors and shRNA-p53 to somatic cells resulted in increased generation of iPS cells (Hong et al., Figure 2). These teachings of Hong et al. provide a strong motivation to include a vector encoding shRNA-p53 in a method of reprogramming a terminally differentiated lymphocyte taught by Mack et al. and Rajesh et al. in order to increase generation of iPS cells from lymphoblastoid cell line cells. In addition, since Rajesh et al. already demonstrates the successful generation of an iPSC by reprogramming LCLs without shRNA-p53, it is maintained that the skilled artisan would have had a reasonable expectation of success in generating an iPSC line product, at any efficiency and any level of reliability, in the presence of shRNA-p53 based on Hong’s teaching that suppressing p53 increases generation of iPS cells from mature terminally differentiated lymphoid cells.
The rejection of claims 33-35 under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication 2012/0009676 (January 12, 2012), hereafter referred to as Mack, in view of Hong et al. (2009) Nature, Vol. 460(7259), 1132-1135, Rajesh et al. (2011) Blood, Vol. 118(7), 1797-1800, U.S. Patent Application Publication 2016/0145642 (2016), hereafter referred to as Cui et al., and U.S. Patent Application Publication 2012/0196360 (August 2, 2012), hereafter referred to as Okita et al., as applied to claims 23-32, and 36-37 above, and further in view of US Patent 8,257,941 (September 4, 2012), hereafter referred to as Sakurada et al., is withdrawn in view of applicant’s amendments, arguments, and the Sareen Declaration for the reasons discussed in detail above.
No claims are allowed.
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 from the examiner should be directed to Anne Marie S. Wehbé, Ph.D., whose telephone number is (571) 272-0737. If the examiner is not available, the examiner’s supervisor, Maria Leavitt, can be reached at (571) 272-1085. For all official communications, the technology center fax number is (571) 273-8300. Please note that all official communications and responses sent by fax must be directed to the technology center fax number. For informal, non-official communications only, the examiner’s direct fax number is (571) 273-0737. For any inquiry of a general nature, please call (571) 272-0547.
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Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634
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