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 without traverse of Group II, drawn to claims 99, 104, and 113-127, in the reply filed on 01/29/2026 is acknowledged.
Priority
The instant application is a 371 of PCT/US2022/014369 filed 01/28/2022, which claims benefit of 63/143,286 filed 01/29/2021.
Information Disclosure Statement
The US patent application publication 20200255801A1 (Daisuke et al.) cited in the IDS filed 01/23/2025 has not been considered. US 20200255801A1, titled “Method for the in vitro preparation of dermal papilla and hair follicle equivalents,” lists Khalid Bakkar and Theebah Sellathurai as the two inventors. “US 20200255801A1 (Daisuke et al.)” is presumed to be a typographical error for US 20200255802A1, which lists Daisuke Kitamura as an inventor and is cited in the IDS filed 01/29/2026.
Specification
The disclosure is objected to because of the following informalities: There are two tables in the specification (p 27 and 29-30), both of which are labeled and referred to as Table 2 (p 26, line 30; p 29, line 21). The first table should be titled (p 27) and referenced (p 26, line 30) as Table 1.
Appropriate correction is required.
Claim Interpretation
Claims 124 and 126 are product-by-process claims. Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. See MPEP 2113. In the instant case, the method steps of claims 123 or 99 do not clearly impart additional structural limitations to the products of claims 124 and 126, respectively. Therefore, claims 124 and 126 are interpreted as “a population of primary B cells transduced with a lentiviral vector.”
The phrase “pharmaceutical composition comprising the population of cells” (claims 125 and 127) is not defined in the specification. Therefore, the broadest reasonable interpretation of this phrase, which includes a composition comprising the population of cells in saline, PBS, or culture medium, is used for the purposes of examination.
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.
Claim(s) 99, 104, 113, and 126-127 are rejected under 35 U.S.C. 103 as being unpatentable over Gong (Molecular Therapy Methods & Clinical Development, 2020, 17: 634-646; cited in IDS 07/28/2023), in view of Janssens (Human Gene Therapy, 2003, 14(3): 263-276).
Regarding claims 99 and 126-127: Gong teaches a method of transducing NK cells by contacting the cells with statins and a lentiviral vector (Abstract). Gong teaches that low-density lipoprotein-receptor (LDLR), the receptor of vesicular stomatitis virus (VSV), is expressed at low levels on NK cells. Gong teaches that transduction efficiency of NK cells with VSV-G pseudotyped lentivirus is augmented by statins that induce higher low-density lipoprotein-receptor (LDLR) expression (Abstract). Gong teaches that in both NK-92 cells and primary NK cells, the transduction efficiency increased after treatment with statins that induce higher LDLR expression, especially with rosuvastatin (Abstract).
Gong teaches that the LDLR expression levels in human B and T lymphocytes can be influenced using compounds compatible with in vitro culture, including statins (Results, para 1).
The method of Gong comprises transduction of NK cells. Gong does not teach a method of transducing primary B cells.
Janssens teaches that human primary B cells can be transduced by VSV-G pseudotyped lentiviral vectors (Abstract). Janssens teaches that gene transfer into primary B cells is a promising strategy to cure genetic diseases associated with B-cell dysfunction, and that long-lasting transgene expression in B cells is of particular interest for immunotherapy for its potential to induce specific immune activation or tolerance (p 263, col 1).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the invention to have modified the method of Gong by transducing primary B cells instead of NK cells. One of ordinary skill in the art would have been motivated to make this modification because Janssens teaches that lentiviral gene transfer into primary B cells is a promising strategy to cure genetic diseases associated with B-cell dysfunction and is of particular interest for immunotherapy. One of ordinary skill in the art would have had a reasonable expectation of making this modification because Janssens teaches that primary B cells can be transduced by VSV-G pseudotyped lentiviral vectors, and Gong teaches that LDLR expression levels in human B cells can be influenced using compounds compatible with in vitro culture (Results, para 1).
Regarding claim 104: Following the discussion of claim 99, Gong teaches the use of rosuvastatin at a final concentration of 20 μM, 5 μM, and 0.5 μM (Materials and Methods, “Co-culture of NK Cells with Statins and Non-Statin Compounds”). The lentiviral vector taught in Gong is a VSV-G pseudotyped vector (Abstract). Janssens teaches isolating human CD19+ primary B cells from the mononuclear cell population of donor blood (reads on human naïve B cells) (p 265, col 1, para 3 – col 2, para 1).
Regarding claim 113: Following the discussion of claim 99, Gong teaches the use of Atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin (Materials and Methods, “Co-culture of NK Cells with Statins and Non-Statin Compounds”).
Claim(s) 99 and 114-125 are rejected under 35 U.S.C. 103 as being unpatentable over Gong (Molecular Therapy Methods & Clinical Development, 2020, 17: 634-646; cited in IDS 07/28/2023), in view of Janssens (Human Gene Therapy, 2003, 14(3): 263-276) and Su (Journal of Immunology, 2016, 197(10): 4163-4176).
Gong, in view of Janssens, renders obvious claim 99.
Regarding claims 114-115 and 118-121: Gong, in view of Janssens, does not teach co-incubating primary B cells with one or more cytokines prior to or simultaneously with the one or more statins.
Su teaches a B-cell culture system in which B-cell populations are expanded on stromal feeder cells that express low levels of CD154 (also called CD40 ligand or CD40L) (claims 118-119) in medium containing the recombinant human cytokines IL-2 (50 ng/mL), IL-4 (10 ng/mL), IL-21 (10 ng/mL), and BAFF (10 ng/mL) (Results, para 1; Materials and Methods, “CD culture system,” para 1) (claims 114-115, 120-121). Su teaches that this culture supports extensive B cell proliferation, with ∼103-fold increases following 8 days in culture and 106-fold increases when cultures are split and cultured for 8 more days (Abstract).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the invention to have modified the method of Gong, in view of Janssens, by co-incubating the primary B cells with IL-2 (50 ng/mL), IL-4 (10 ng/mL), IL-21 (10 ng/mL), and BAFF (10 ng/mL) on feeder cells that express CD40 ligand, as taught in Su. One of ordinary skill in the art would have been motivated to make this modification because Su teaches that a B-cell culture system in which B-cell populations are expanded on stromal feeder cells that express low levels of CD40 ligand in medium containing the recombinant human cytokines IL-2 (50 ng/mL), IL-4 (10 ng/mL), IL-21 (10 ng/mL), and BAFF (10 ng/mL) supports extensive B cell proliferation (Results, para 1; Materials and Methods, “CD culture system,” para 1; Abstract). One of ordinary skill in the art would have had a reasonable expectation of making this modification because Su teaches that primary B cells can be co-incubated with feeder cells and cytokines.
Regarding claims 116-117 and 122-125: Following the discussion of claim 99, Gong teaches the use of Atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin (Materials and Methods, “Co-culture of NK Cells with Statins and Non-Statin Compounds”).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Risa Takenaka whose telephone number is (571)272-0149. The examiner can normally be reached M-F, 12-7 EST.
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/RISA TAKENAKA/ Examiner, Art Unit 1632
/PETER PARAS JR/ Supervisory Patent Examiner, Art Unit 1632