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 .
Election/Restrictions
Applicant’s election of Group II (claims 11 and 14-20) in the reply filed on May 22, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). In addition, Applicants also elected the species of the combination of OCT/KLF/MYC/SOX proteins. Applicants previously canceled claims 1-7 and 9-10 and further canceled claims 8 and 11-30, and added new claims 31-50. Claims 31-39 read on the elected invention. Claims 40-50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 22, 2026.
In addition, upon further consideration, the election of species requirement is withdrawn, and claims 31-39 will be examined in their entirety.
Information Disclosure Statement
The Information Disclosure Statements filed June 14, 2024 and May 22, 2026 have been considered.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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.
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 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 31-33 and 35-38 are rejected under 35 U.S.C. 103 as being unpatentable over Su et al. (8(5) PLOS ONE e64496 1-10 (2013), and cited in the Information Disclosure Statement filed June 14, 2024) or Baylink et al. (PCT Patent Application Publication No. WO 2013/177228, published November 28, 2013, and cited in the Information Disclosure Statement filed June 14, 2024) in view of Sun et al. (88(4) Journal of Virology 2035-2046 (2014) or Hu (23(12) Stem Cells and Development 1301-1315 (2014)).
Regarding claim 31, Su discloses generation of induced pluripotent stem cells (iPSCs) by contacting cells from cord blood with an episomal vector (abstract). Su discloses that the vector includes BCL-xL and the Yamanaka factors OCT4, SOX2, KLF4, and MYC (abstract).
Regarding claim 35, Su discloses that the genes are under the control of the spleen focus forming virus promoter (abstract).
Regarding claim 37, Su discloses that, in order to drive expression of two genes, an equine rhinitis A virus 2A self-cleavage peptide was used to link the two genes (page 7, column 1, second full paragraph).
Regarding claim 1, Baylink discloses a vector for generating induced pluripotent stem cells from human target cells (abstract). Baylink discloses that the vector includes two, three, or four transcription and reprogramming factors, each separated by a 2a self-cleavage site (abstract). Baylink discloses that the reprogramming factors are Yamanaka factors KLF4, MYC, OCT2, and SOX2 or Thomson/Yu factors LIN28, NANOG, OCT4, and SOX2 (paragraph [0004]). Baylink discloses that the vector includes the anti-apoptotic factor BCL-xL (paragraph [0010]-[0011]).
Regarding claim 35, Baylink discloses that the genes are under the control of the spleen focus forming virus promoter abstract).
Regarding claim 37, Baylink discloses that a 2A self-cleavage peptide is included between genes (paragraph [0024]).
Neither Su nor Baylink disclose the use of an alphavirus vector that includes the claimed genes. Neither Su nor Baylink explicitly disclose the order of the genes in the vector.
Regarding claim 31, Sun discloses engineered alphavirus expression vectors that express reporter proteins (abstract).
Regarding claim 32, Sun discloses that the alphavirus expression vector can be a Venezuelan equine encephalitis virus (VEEV) vector (abstract/importance and page 2036, paragraph bridging paragraphs 1 and 2). Sun discloses that the VEEV construct can include the VEEV genes nsP1, nsP2, nsP3, and nsP4 (Figure 1).
Regarding claim 33, Sun discloses that alphavirus vectors expressing reporters of infection are useful for such analysis for viral replication, which is interpreted as being self-replicative (abstract).
Regarding claim 35, Sun discloses that the transgenes are under the expression of a promoter, which can be a 5’ 26S promoter (page 2035, paragraph bridging columns 1 and 2 and paragraph bridging pages 2035 and 2036).
Regarding claim 36, Sun discloses that the transgenes are under the expression of a promoter, which can be a 5’ 26S promoter (page 2035, paragraph bridging columns 1 and 2 and paragraph bridging pages 2035 and 2036).
Regarding claim 37, Sun discloses the use of a 2A self-cleavage peptide (page 2036, paragraph bridging columns 1 and 2 and Figure 1).
Regarding claim 31, Hu discloses engineered alphavirus expression vectors that express reporter proteins (page 1310, paragraph bridging columns 1 and 2).
Regarding claim 32, Hu discloses that the alphavirus expression vector can be a Venezuelan equine encephalitis virus (VEEV) vector (page 1310, paragraph bridging columns 1 and 2). Sun discloses that the VEEV construct can include the VEEV genes nsP1, nsP2, nsP3, and nsP4 (Figure 1).
Regarding claim 33, Hu discloses that alphavirus vectors expressing reporters of infection can replicate in cells, which is interpreted as being self-replicative (page 1310, paragraph bridging columns 1 and 2).
Regarding claim 35, Hu discloses that the transgenes are under the expression of a promoter, which can be a 5’ 26S promoter (page 1310, paragraph bridging columns 1 and 2).
Regarding claim 36, Sun discloses that the transgenes are under the expression of a promoter, which can be a 5’ 26S promoter (page 1310, paragraph bridging columns 1 and 2).
Regarding claim 37, Hu discloses the use of a 2A self-cleavage peptide and internal ribosome entry sites (IRESs) (page 1310, paragraph bridging columns 1 and 2).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to substitute Sun’s VEEV alphavirus vector for the vectors of either Su or Baylink because each of the vectors are well-known vectors for expressing transgenes in cells. As such, one of ordinary skill in the art would have been motivated to use Sun’s or Hu’s VEEV vectors since they are self-replicative and can be used for high expression levels of transgenes in cells. Thus, one of ordinary skill in the art would have had a predictable and reasonable expectation of success in using Sun’s or Hu’s VEEV vectors in place of Su’s or Baylink’s vectors having the BCL-xL and reprogramming OCT4, KLF4, SOX2, and MYC genes.
Regarding the order of the components of the vector disclosed and suggested by the combination of Su or Baylink with Sun or Hu, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to order the components separated by 2A peptides and IRES sequences in such a way that the vectors and transgenes being expressed are functioning at an optimal level. One of ordinary skill in the art would have been motivated to provide an order of the claimed genes that provides for optimal expression of transgenes, as well as optimal level of producing induced pluripotent stem cells.
Claims 34 and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Su or Baylink in view of Sun or Hu as applied to claims above, and further in view of June et al. (U.S. Patent No. 6,143,291, issued November 7, 2000), Yamanaka (U.S. Patent No. 7,250,255, issued July 31, 2007), Schlegel et al. (U.S. Patent Application Publication No. 2003/0108963, published June 12, 2003), Gure et al. (U.S. Patent Application Publication No. 2004/0126808), published July 1, 2004), and Masuda et al. (U.S. Patent No. 7,241,581, issued July 10, 2007).
Su, Baylink, Sun, and Hu disclose and suggest alphavirus vectors, as discussed above.
Su, Baylink, Sun, and Hu fail to disclose or suggest the specific sequences of BCL-xL, OCT4, KLF4, SOX2, and/or c-MYC.
June discloses that contacting a T cell with an agent that augments BCL-xL, which protects the cell from cell death (abstract). June discloses a sequence of BCL-xL that is identical to instant SEQ ID NO: 1 (SEQ ID NO: 2) (Appendix I).
Yamanaka discloses probes for selecting ES cells (abstract). Yamanaka discloses a sequence that encodes a protein comprising the sequence of instant SEQ ID NOS: 3 and 4 (i.e., OCT4) (column 5, lines 43-47 and SEQ ID NO: 40) (Appendix II).
Schlegel discloses proteins that are associated with prostate cancer and compositions for detection of prostate cancer (abstract). Schlegel discloses KLF4 protein that comprises the sequence of instant SEQ ID NO: 5 (SEQ ID NO: 210) (Appendix III).
Gure discloses cancer associated antigens which have been identified as being expressed in small cell lung cancer (abstract). Gure discloses SOX2 comprising the sequence of instant SEQ ID NO: 7 (SEQ ID NO: 19) (Appendix IV).
Masuda discloses methods of identifying compounds that can modulate IL-4 receptor-mediated IgE production (abstract). Masuda discloses use of c-MYC as a surrogate analyte (abstract). Masuda discloses a sequence of c-MYC that comprises instant SEQ ID NO: 9 (SEQ ID NO: 21) (Appendix V).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to use the BCL-xL, OCT4, KLF4, SOX2, and c-MYC sequences of Junes, Yamanaka, Schlegel, Gure, and/or Masuda in the alphavirus vector disclosed and suggested by Su, Baylink, Sun, and/or Hu because the vector of Su, Baylink, Sun, and/or Hu includes these genes. As such, because each of the sequences required by the claims was known, as disclosed by Junes, Yamanaka, Schlegel, Gure, and/or Masuda, one of ordinary skill in the art would be able to determine and employ the desired sequences in an alphavirus vector, as disclosed and suggested by Su, Baylink, Sun, and/or Hu.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 31-32, 34-37, and 39 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 51, of copending Application No. 17/704,922 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘922 application claims a method of obtaining a population of induced pluripotent cells from hematopoietic lineage cells by introducing an alphavirus expression construct comprising Venezuelan equine encephalitis virus (VEEV) nsP1, nsP2, nsP3, and nsP4 genes and directs expression of a BCL-xL protein comprising SEQ ID NO: 1 or an amino acid sequence having 95% identity thereto, and including an OCT4 protein comprising SEQ ID NO: 3, a KLF protein comprising SEQ ID NO: 5, a SOX2 protein comprising SEQ ID NO: 7, a c-MYC protein comprising SEQ ID NO: 9, or amino acid sequences having at least 95% identity to these sequences. The instant application claims an alphavirus RNA expression construct encoding the same sequences as claimed by the ‘922 application.
Regarding claim 31, the ‘922 application claims a method of obtaining a population of induced pluripotent cells by introducing a VEEV RNA expression construct comprising BCL-xL and an additional reprogramming factor selected from an OCT family protein, a KLF family protein, a MYC family protein, a SOX family protein, a LIN28 protein, a NANOG protein, and a p53 dominant negative protein (claim 51).
Regarding claim 32, the ‘922 application claims that the alphavirus expression vector construct is a VEEV RNA expression construct comprising VEEV nsP1, nsP2, nsP3, and nsP4 genes (claim 51).
Regarding claim 34, the ‘922 application claims that the alphavirus RNA expression construct comprises a BCL-xL protein comprising SEQ ID NO: 1 or an amino acid sequence having 95% identity thereto, and including an OCT4 protein comprising SEQ ID NO: 3, a KLF protein comprising SEQ ID NO: 5, a SOX2 protein comprising SEQ ID NO: 7, a c-MYC protein comprising SEQ ID NO: 9, or amino acid sequences having at least 95% identity to these sequences (claim 51).
Regarding claim 35, the ‘922 application claims that the BCL-xL and additional reprogramming factors are under the control of a common promoter (claims 58).
Regarding claim 36, the ‘922 application claims that the promoter is a 26S promoter (claim 59).
Regarding claim 37, the ‘922 application claims that the coding sequences for the BCL-xL and reprogramming factors are separated by a coding sequence for a 2A peptide (claim 60).
Regarding claim 39, the ‘922 application claims that the sequences of the BCL-xL protein comprises SEQ ID NO: 1, the OCT4 protein comprises SEQ ID NO: 3, the KLF protein comprises SEQ ID NO: 5, the SOX2 protein comprises SEQ ID NO: 7, and the c-MYC protein comprises SEQ ID NO: 9s (claim 61).
Therefore, the claims are not deemed to be patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Kumano et al. (98 International Journal of Hematology 145-152 (2013), and cited in the Information Disclosure Statement filed June 14, 2024) disclose generation of iPS cells from hematopoietic cells (abstract). As noted in the cited prior art above, Kumano discloses use of four factors (OCT4, SOX2, KLF4, and c-MYC) are involved with reprogramming cells (page 146, column 2, final full paragraph and paragraph bridging pages 146 and 147).
Focosi et al. (4 Blood Cancer Journal e211, 1-8 (2014), and cited in the Information Disclosure Statement filed June 14, 2024) disclose generation of induced pluripotent stem cells by reprogramming adult somatic cells with transcription factors OCT4, KLF4, SOX2, and c-MYC, as also noted in the cited prior art above (abstract and page 1, column 1, second paragraph).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, NEIL HAMMELL can be reached at (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636
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