Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Election/Restrictions
Applicant’s election of Group I in the reply filed on 06/17/25 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)).
Claim Status
Claims 1-44 are pending. Claims 6-30, and 33-44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Claims 1-5, 31 and 32 are pending and are under consideration.
Information Disclosure Statement
The IDS filed 11/17/2021 was fully considered except for Item 26, (non-patent literature, Ghosh et al.) as the reference could not be found in any of the parent applications.
Claim Rejections - 35 USC § 102/103
The following is a quotation of the appropriate paragraphs of pre-AIA 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) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
Claim(s) 1-5, and 31-32 is/are rejected under pre-AIA 35 U.S.C. 102 (a) as anticipated by or, in the alternative, under pre-AIA 35 U.S.C. 103(a) as obvious over Song et al. (J Immunother. Volume 33, Number 8, October 2010, page 865).
Claim(s) 1-5, and 31-32 is/are rejected under pre-AIA 35 U.S.C. 102(a) as being anticipated by Song et al. (J Immunother. Volume 33, Number 8, October 2010, page 865)
Song et al. teach an isolated nucleic acid sequence encoding a chimeric antigen receptor, wherein the isolated nucleic acid sequence comprises a nucleic acid sequence encoding an α-folate receptor antibody (MOv19) coupled to a CD3 zeta chain. As evidenced by the specification, instant SEQ ID NO:15 is equivalent to the folate receptor alpha binding domain and is referenced as MOv19 (see Figure 30, reprinted below). Further, while the prior art does not teach that the CD3 zeta signaling domain is encoded by SEQ ID NO:7 and comprises the amino acids of SEQ ID NO:19, the specification references [0065] CD3 zeta signaling domains generically and thus the prior art is either anticipatory or the incorporation of the claimed sequences would have been obvious. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Further, regarding Claims 31-32, the abstract teaches “using in vitro assay systems, both MOv19-ζ and MOv19-BB-ζ transduced T cells”. Absent evidence to the contrary, the MOv19-BB-ζ comprises the nucleic acid sequences of SEQ ID NO:1 (See Figure 30) and encodes SEQ ID NO:13 as claimed in Claims 31-32. Regarding claim 5, the abstract teaches that the scFv (MOv19) was “coupled” to an inactive form of the CD3-zeta “intracellular” domain. If the antigen binding region is extracellular but is coupled to an intracellular domain then it would appear that a “transmembrane” domain was inherently present.
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Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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.
Claim 1-5, and 31-32 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Coney et al. (Cancer Research, 54, May 1, 1994) and Figini et al. (Cancer Immunology, Immunothreapy, Vol. 58, August 15, 2008) in further view of Dotti et al. Human Gene Therapy, Vol. 20, November 2009, Applicant’s IDS).
The claims are drawn to an isolated nucleic acid encoding a chimeric antigen receptor wherein the isolated nucleic acid comprises a nucleic acid encoding an α-folate receptor antibody comprising the amino acid sequence of SEQ ID NO:15 (also known as MOv19). The claims further include known generic structural aspects of CARs such as a CD3 zeta signaling domain (Claim 2) and a transmembrane domain (Claim 5). The claims further include a nucleic acid (SEQ ID NO:7- Claim 4) that encodes a CD3 zeta signaling domain of SEQ ID NO:19 (Claim 3). Claims 31 and 32 include the nucleic acid (SEQ ID NO:1) that encodes a CAR (SEQ ID NO:13) comprising MOv19--4-1BB—CD3zeta.
Coney et al. teach that the human folate binding receptor is overexpressed on 90% of nonmucinous epithelial ovarian tumors (abstract). Coney et al. describe the construction and expression of chimeric, mouse-human MOv18 and MOv19 monoclonal antibodies (page 2448, 2nd column through 2449) that bind the human folate receptor. Coney et al. observed antibody-dependent cell cytotoxicity (ADCC) against various ovarian cancer cell lines using both murine and chimeric MOv18 and MOv19 monoclonal antibodies (Table 2).
Figini et al. teach (introduction) that the folate receptor is a member of the family of homologous proteins that bind folic acid with high affinity and is overexpressed on 90% of epithelial ovarian carcinomas. The receptor can be blocked at the membrane level using an intracellular antibody to partially revert the tumor phenotype. Figini et al also teach that they previously developed a panel of anti-ovary carcinoma murine mAbs subsequently shown to recognize different epitopes of the folate receptor. Two of these mAbs, MOv18 (IgG1) and MOv19 (IgG2a), bound to ovarian tumor cells with high affinity and were further exploited for therapeutic approaches. Encouraging results were obtained in two clinical phase II studies in which we used a murine anti-FR mAb, delivered intraperitoneally, to target 131I or to recruit the cytotoxicity of activated autologous T cells to epithelial ovarian carcinoma.
Neither Coney et al. nor Figini et al. teach construction of a chimeric antigen receptor comprising an α-folate receptor antibody.
Dotti et al. teach (abstract) that ‘‘T-body’’ or chimeric antigen receptor (CAR) technology, which combines the specificity of an antibody with the homing, tissue penetration, and target cell destruction of T cells, was first described in 1993. Dotti et al. further teach (pages 1229-1230) that CARS are advantageous over the native antibodies because of their physical association with effector T cells. CAR-modified T cells have an active biodistribution, with migration through multiple tissue planes along chemokine gradients and can recruit multiple cytotoxic effector mechanisms available to a T cell, rather than the more restricted cytotoxic machinery associated with the Fc component of an antibody. Dotti et al. further teach (Figure 1, and below) the common structures of first, second, and third generation CARs including the CD3 zeta chain and at least two costimulatory molecules such as the endodomain of 4-1BB or CD28.
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It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to adapt the MOv19 anti-folate receptor antibody as taught by Coney et al. and Figini et al. so as to construct a chimeric receptor antibody as taught by Dotti et al. One would have been motivated to do so because Coney et al. and Figini et al. taught that MOv19 antibodies successfully targeted the folate receptor on ovarian cancer cells and partially reverted the tumor phenotype. Moreover, Dotti et al. clearly teaches the advantages of chimeric antigen receptor technology wherein CARS are advantageous over the native antibodies because of their physical association with effector T cells. CAR-modified T cells have an active biodistribution, with migration through multiple tissue planes along chemokine gradients and can recruit multiple cytotoxic effector mechanisms available to a T cell, rather than the more restricted cytotoxic machinery associated with the Fc component of an antibody. Thus, one of ordinary skill in the art would have constructed a CAR for the purposes of targeting the folate receptor on tumor cells comprising the amino acid sequence of SEQ ID NO:13 (MOv19--4-1BB—CD3zeta) because all of the sequences were known and the advantages of CAR technology were known. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643