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 .
Claims 1-3, 5-7, 13, 18-20, 28-30, 33-35 and 42-45 are pending in the present application.
Applicant’s election without traverse of Group I, drawn to a T cell, wherein Ryr2 gene is deleted in the T cell, in the reply filed on 12/29/2025 is acknowledged.
Applicant also elected without traverse the species of exon 7 of the Ryr2 gene is deleted.
Accordingly, claims 6-7, 13, 18-20, 28-30, 33-35 and 44-45 were withdrawn from further consideration because they are directed to non-elected inventions. Additionally, claims 3 and 42-43 were also withdrawn from further consideration because they are drawn to non-elected species.
Therefore, claims 1-2 and 5 are examined on the merits herein with the above elected species.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Takeshima et al (EMBO J. 17:3309-3316, 1998) and evidenced by Rudd (Annu. Rev. Immunol. 38:229-247, 2020).
The instant claims encompass a T cell in vitro or in vivo, preferably a Tconv cell (a conventional T cell), wherein Ryr2 gene is deleted in the T cell.
Takeshima et al already disclosed at least E8.5, E9.5 mouse embryos homozygous for crrm2 and mouse neonates heterozygous for crrm2, wherein in the crrm2 allele the first protein coding sequence of 48 base pairs and the partial sequence of the first intron are deleted from the RyR-2 gene (page 3310, right column, bottom of first paragraph; Fig. 1 and Table 1). With respect to the E9.5 mouse embryos homozygous for crrm2, Takeshima et al stated “[i]n the E9.5 mutant embryos, we could not detect clear histological abnormalities in the developing neural tubule, blood vessels or primitive digestive organs, that contain immature neurons or smooth muscle cells” (page 3311, right column, bottom of second full paragraph). Takeshima et al also disclosed that morphological and physiological experiments revealed no significant differences were observed between wild type and +/crrm2 mice (page 3311, left column, last sentence of first paragraph). At least mouse neonates heterozygous for crrm2 comprise T cells, including conventional T cells, whose genomes having a deleted RyR-2 gene in an allele, that are identical to the claimed T cell of the present application. The existence of CD4+ and CD8+ T cells in neonates is evident by the Rudd review (Abstract).
Accordingly, the teachings of Takeshima et al meet every limitation of the instant claims. Therefore, the refence anticipates the instant claims.
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.
Alternatively, claims 1 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Takeshima et al (EMBO J. 17:3309-3316, 1998) and evidenced by Rudd (Annu. Rev. Immunol. 38:229-247, 2020).
The instant claims encompass a T cell in vitro or in vivo, preferably a Tconv cell (a conventional T cell), wherein Ryr2 gene is deleted in the T cell.
Takeshima et al already disclosed at least E8.5, E9.5 mouse embryos homozygous for crrm2 and mouse neonates heterozygous for crrm2, wherein in the crrm2 allele the first protein coding sequence of 48 base pairs and the partial sequence of the first intron are deleted from the RyR-2 gene (page 3310, right column, bottom of first paragraph; Fig. 1 and Table 1). With respect to the E9.5 mouse embryos homozygous for crrm2, Takeshima et al stated “[i]n the E9.5 mutant embryos, we could not detect clear histological abnormalities in the developing neural tubule, blood vessels or primitive digestive organs, that contain immature neurons or smooth muscle cells” (page 3311, right column, bottom of second full paragraph). Takeshima et al also disclosed that morphological and physiological experiments revealed no significant differences were observed between wild type and +/crrm2 mice (page 3311, left column, last sentence of first paragraph).
Although Takeshima et al did not explicitly mention T cells or Tconv cells, it would have been obvious for an ordinary skill in the art to recognize that at least the disclosed mouse neonates heterozygous for crrm2 comprise T cells, including conventional T cells, whose genomes having a deleted RyR-2 gene in an allele, and such T cells are indistinguishable and encompassed by the claimed T cell of the present application. The existence of CD4+ and CD8+ T cells in neonates is evident by the Rudd review (Abstract).
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Takeshima et al (EMBO J. 17:3309-3316, 1998) and evidenced by Rudd (Annu. Rev. Immunol. 38:229-247, 2020) as applied to claims 1 and 5 above, and further in view of Kannankeril et al (PNAS 103:12179-12184, 2006).
The instant claim encompasses a T cell in vitro or in vivo, wherein exon 7 of the Ryr2 gene is deleted in the T cell.
The teachings of Takeshima et al were already presented above. However, Takeshima et al did not teach specifically the generation and characterization of knockout mice lacking RyR-2 by targeting exon 7 of the mouse RyR-2 gene instead of the first exon of the mouse RyR-2 gene.
Before the effective filing date of the present application (05/15/2020), Kannakeril et al already disclosed that a genomic clone containing exons 7 and 8 of the mouse RyR2 gene was isolated, and a targeting vector derived from said genomic clone was constructed to introduce the human disease-associated RyR2 mutation R176Q mutation into knock-in mice (Abstract; particularly section titled “Generation of knockin mice with the RyR2 R176Q mutation” at page 12183; and Fig. 1A).
Accordingly, it would have been obvious for an ordinary skilled artisan to modify the teachings of Takeshima et al by also targeting exon 7 of the mouse RyR-2 gene to generate knockout mice lacking RyR-2 for the characterization of the mutant mice, in light of the teachings of Kannakeril et al as set forth above.
An ordinary skilled artisan would have been motivated to carry out the above modification because a genomic clone containing exons 7 and 8 of the mouse RyR2 gene was already isolated by Kannakeril et al for constructing a targeted vector. Please note that the primary Takeshima reference already taught that a genomic DNA clone carrying the first exon of the mouse RyR-2 gene was first isolated to construct a targeting vector for the generation of mice lacking RyR-2.
An ordinary skilled artisan would have a reasonable expectation of success in light of the teachings of Takeshima et al and Kannakeril et al; coupled with a high level of skill for an ordinary skilled artisan in the relevant art.
The modified teachings resulting from the combined teachings of Takeshima et al and Kannakeril et al as set forth above would result in the generation of mouse embryos homozygous for a deletion in exon 7 of the Ryr2 gene and mouse neonates heterozygous for a deletion in exon 7 of the Ryr2 gene; and at least the mouse neonates comprise T cells whose genomes having a deleted exon 7 of the RyR-2 gene in an allele, and such T cells are indistinguishable and encompassed by the claimed T cell of the present application.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Yoshimoto et al (Blood 119:5706-5714, 2012) demonstrated the existence of T cell-restricted progenitors in the E9.5 extra-embryonic yolk sac (YS) in the mouse embryo, that directly engraft in recipient immunodeficient mice (Abstract).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Quang Nguyen, Ph.D., at (571) 272-0776.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s SPE, James Douglas (Doug) Schultz, Ph.D., may be reached at (571) 272-0763.
To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Group Art Unit 1631; Central Fax No. (571) 273-8300.
Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to (571) 272-0547.
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/QUANG NGUYEN/Primary Examiner, Art Unit 1631