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 50- 64 are pending and under examination.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 50-53, 55-57, 59, 60, 62 and 63 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Chuang et al. (WO2018177371, cited herewith).
Chuang teaches various bispecific antibodies comprising EGFR- and CD3-binding domains (see, e.g., at paras 69, 135-138; claims 1 and 7; Fig. 3(c)). An alignment of (i) SEQ ID NOs: 63+78+79 of the “anti-EGFR scFv/anti-CD3 scFv BsAb” described in Chuang Table 7 with (ii) SEQ ID NO: 32, (ii) SEQ ID NO: 42, (iii) SEQ ID NO: 43, and (iv) amino acids 494-1003 of SEQ ID NO: 35 of the instant claims is set forth below:
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As shown above, the “anti-EGFR scFv/anti-CD3 scFv BsAb” described in Chuang Table 7 comprises SEQ ID NOs: 32, 42 and 43 of the instant claims.
A difference between amino acids 494-1003 of SEQ ID NO: 35 and the “anti-EGFR scFv/anti-CD3 scFv BsAb” described in Chuang Table 7 is that one additional residues (R, Arg) lies at the C-terminus of the anti-EGFR scFv light chain in the construct of Chuang:
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While all of the BsAbs described in Chuang use these same EGFR-binding variable domains; in the working examples demonstrating, e.g., the cancer cell killing activity of EGFRxCD3 bispecific antibodies (see Chuang at paras 227-228; Figs. 27A and 27C), the EGFRxCD3 bispecific antibodies of Chuang employ an “anti-EGFR Fab/anti-CD3 scFv” format (see Chuang Fig. 3A) instead of a single chain “BiTE” format like the “anti-EGFR scFv/anti-CD3 scFv BsAb” described in Chuang Table 7 (Chuang SEQ ID NOs: 63+78+79) comprising SEQ ID NOs: 32, 42 and 43 of the instant claims (see Chuang Fig. 3C).
Despite this difference in format, the skilled artisan would understand from the working examples of Chuang that bispecific antibodies comprising SEQ ID NOs: 32, 42 and 43 of the instant claims are effective in cancer cell killing. Moreover, consistent, e.g., with the teachings of Chuang at claims 1, 3 and 7, the ordinarily skilled artisan would understand that a bispecific antibody based the structure of the “anti-EGFR scFv/anti-CD3 scFv BsAb” described in Chuang Table 7 (Chuang SEQ ID NOs: 63+78+79, consistent with Chuang Fig. 3C), comprising SEQ ID NOs: 32, 42 and 43 of the instant claims will be useful in treatment of a subject afflicted with an EGFR-expressing cancer (see Chuang at claim 12->10->7->3->2->1).
Finally, beginning at para 102 Chuang teaches the production of their bispecific antibodies by combining the appropriate “nucleic acids encoding the anti-tumor antigen (e.g., anti-PSMA, anti-EGFR, anti-PD-LI and etc) and anti-CD3 were grafted and fused with other DNA sequence ( e.g., signal peptide, IRES, linker and etc) into desired constructs via whole gene synthesis,” which were then “…amplified in Expi293 cells 20 (7.5x107 cell/25.5 mL, with the addition of 30μg nucleic acids for transfection), which were cultured at 37 °C in an atmosphere of 8% CO2 in air. BsAbs were purified from the culture media collected after 6 days by Ni-Affinity chromatography, and the concentration was determined by use of Pierce™ BCA Protein Assay kit.” (see paras 103-104).
Note that along with the teachings of Chuang directed to various bispecific antibodies comprising EGFR- and CD3-binding domains (see, e.g., at paras 69, 135-138; claims 1 and 7; Fig. 3(c)), Chuang also discloses the nucleic acids encoding said bispecific antibodies:
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Thus, the teachings of Chuang anticipate claims 50-53, 55-57, 59, 60, 62 and 63.
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) 58 is rejected under 35 U.S.C. 103 as being unpatentable over Chuang et al. (WO2018177371) as applied to claims 50-53, 55-57, 59, 60, 62 and 63 above and further in view of Harpoon (WO2016187594, cited on an IDS).
The teachings of Chuang as applied to claims 50-53, 55-57, 59, 60, 62 and 63 are set forth above.
However, Chuang does not anticipate the polypeptide comprising amino acids 494-1003 of SEQ ID NO: 35.
Harpoon teaches “trispecific antigen-binding proteins” (“trisp”) comprising EGFR-, CD3- and human serum albumin (HSA) binding domains as described in Tables 6 and 7 which set forth SEQ ID NOs: 1-48 (see para 36). One particular trisp comprising EGFR-, CD3- and human serum albumin (HSA) binding domains which is featured in the working example of Harpoon is designated “EGFR-scFv:C:A,” which is also described as “anti-EGFR-scFv:anti-CD3EscFv:anti-ALB-sdAb.” (see para 133). This particular trisp, which is disclosed as SEQ ID NO: 8 and displayed in Table 7 of Harpoon, comprises an EGFR-scFv which is identical to SEQ ID NO: 42 of the instant claims.
As described in para 133, and as shown in para 145, the “EGFR-scFv:C:A” trisp is the least affected by the presence of albumin (which will bind to the anti-ALB-sdAb of SEQ ID NO: 8) as compared to other EGFR trisps disclosed by Harpoon (compare Tables 3 and 4 in paras 144-45 of Harpoon).
Given the reference teachings it would have been obvious to one of ordinary skill in the art that the EGFR-scFv of Harpoon SEQ ID NO: 8 could be substituted for the EGFR-scFv of the “anti-EGFR Fab/anti-CD3 scFv” comprising SEQ ID NOs: 63+78+79 of Chuang with a reasonable expectation that the resultant construct comprising the EGFR-scFv of Harpoon SEQ ID NO: 8 joined to SEQ ID NOs: 63 and 79 of Chuang will functional the same as a polypeptide comprising SEQ ID NOs: 63+78+79 of Chuang.
Note in this regard that the simple substitution of one known element for another to obtain a predictable result is considered a priori obvious consistent with the teachings of MPEP § 2141(III).
In view of the reference teachings it was apparent that one of ordinary skill in the art would have had a reasonable expectation of success in arriving at the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claim(s) 54, 61 and 64 are rejected under 35 U.S.C. 103 as being unpatentable over Chuang et al. (WO2018177371) as applied to claims 50-53, 55-57, 59, 60, 62 and 63 above and further in view of Chang et al. (20160361360, cited herewith).
The teachings of Chuang as applied to claims 50-53, 55-57, 59, 60, 62 and 63 are set forth above.
However, Chuang does not anticipate the polypeptide claim 54, or the vector and cell of claims 61 and 64, respectively.
With respect to guiding the secretion of an antibody with a CD8 leader sequence, Chang teaches such at claim 61. Moreover, Chang teaches various techniques for the antibody cloning and production including the use of expression vector DNA for antibody production and further the use of a mammalian immune cells, such as various Sp2/0 myeloma cell lines for the expression of said vectors comprising antibody encoding nucleic acids (see paras 111-115).
Thus, given the reference teachings it would have been obvious to one of ordinary skill in the art that, e.g., a CD8 leader sequence may be substituted for the IgK leader sequence disclosed in Chuang with the predictable result of directing the antibody of Chuang into the exocytic secretory pathway. Moreover, it further would have been obvious to one of ordinary skill in the art that the antibody cloning and production techniques described by Chang provide a convenient means to produce the desired product via a system pre-adapted for transfection, growth and expression in serum-free medium, thereby ensuring for efficient production in a setting that minimizes microbial contamination of mammalian cultures (serum-fee).
In view of the reference teachings it was apparent that one of ordinary skill in the art would have had a reasonable expectation of success in arriving at the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made.
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 50-60, 62-63 and rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 12378297, cited herewith.
Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims anticipate the instant claims because in preparing a chimeric antigen receptor (CAR) T cell comprising a heterologous nucleic acid molecule, wherein the heterologous nucleic acid molecule comprises: (a) a first polynucleotide encoding a CAR comprising an antigen-binding domain, a transmembrane domain, and an intracellular signaling domain; and (b) a second polynucleotide encoding a bispecific T cell engager (BiTE), wherein the CAR and the BiTE are produced in the form of a polyprotein, wherein: the polyprotein comprises, from N-terminal to C-terminal: the CAR, a P2A peptide, and the BiTE; the CAR comprises amino acids 1-469 of SEQ ID NO: 35; the P2A peptide comprises the amino acid sequence of SEQ ID NO: 40; and the BiTE comprises amino acids 494-1003 of SEQ ID NO: 35 (claim 24); or in preparing chimeric antigen receptor (CAR) T cell comprising a heterologous nucleic acid molecule, wherein the heterologous nucleic acid molecule comprises: (a) a first polynucleotide encoding a CAR comprising an antigen-binding domain, a transmembrane domain, and an intracellular signaling domain; and (b) a second polynucleotide encoding a bispecific T cell engager (BiTE), wherein the CAR and the BiTE are produced in the form of a polyprotein, wherein : the antigen-binding domain comprises an EGFRVIII antigen binding domain comprising the amino acid sequence of SEQ ID NO: 36: the transmembrane domain comprises a CD8 hinge/transmembrane domain comprising the amino acid sequence of SEQ ID NO: 37; the intracellular signaling domain comprises: a 4-1BB intracellular domain comprising the amino acid sequence of SEQ ID NO: 38; and a CD3ζ intracellular signaling domain comprising the amino acid sequence of SEQ ID NO: 39; the BiTE comprises: an IgK leader comprising the amino acid sequence of SEQ ID NO: 41; an EGFR binding domain comprising the amino acid sequence of SEQ ID NO: 42; and a CD3 binding domain comprising the amino acid sequence of SEQ ID NO: 43; and the polyprotein comprises, a P2A peptide between the CAR and the BiTE, wherein the P2A peptide comprises the amino acid sequence of SEQ ID NO: 40 (claim 23), the skilled artisan will necessarily be making the bispecific antibodies, polynucleotides and host cells of the instant claims.
No claims are allowed.
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/ZACHARY S SKELDING/Primary Examiner, Art Unit 1644
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