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 .
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 25, 55-58 are rejected under 35 U.S.C. 101 because
the claimed invention is directed to a natural phenomenon (product of nature) without significantly more. The claims recite amino acid sequences “domain” derived from the CD40 protein. The claims are concerned with a “CD40 domain” which comprises one or more of the “Consensus A through C” as indicated. However regarding the claimed consensus for example embodiment of the large genus of sequences claimed are identically found in the naturally occurring human CD40 molecule as the intracellular portion of Uniprot P25942 (consensus residues 216-277) as represented below.
KKVAKKPTNKAPHPKQEPQEINFPDDLPGSNTAAPVQETLHGCQPVTQEDGKESRISVQERQ.
As bolded above the sequence PQEINF satisfies the requirement of claim 25 consensus C as well as claim “56” , “PQEINF” as a “TRAF6” domain. The amino acid phenylalanine “F” is a “aromatic” amino acid as Regarding the claim 55 the sequence 475 represents identically the 24 C terminal amino acid sequences of P25942 as indicated aligned below.
Qy 1 TLHGCQPVTQEDGKESRISVQERQ 24
||||||||||||||||||||||||
Db 39 TLHGCQPVTQEDGKESRISVQERQ 62
Regarding the claim “57”, the sequence PVQET is similarly found in the naturally occurring CD40 sequence as underlined/bolded above. Regarding claim “58” the sequence SVQE is similarly found in the naturally occurring CD40 intracellular signalling domain as underlined and bolded above.
This judicial exception is not integrated into a practical application because only amino acid sequences are claimed . The claim(s) does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the Applicant simply claims amino acid sequences which are found as a naturally occurring product of nature.
Claim Objections
The numbering of claims is not in accordance with 37 CFR 1.126 which requires the original numbering of the claims to be preserved throughout the prosecution. When claims are canceled, the remaining claims must not be renumbered. When new claims are presented, they must be numbered consecutively beginning with the number next following the highest numbered claims previously presented (whether entered or not).
Misnumbered claims “54-55-56” have been renumbered as claims “56-57-58” for the purposes of the rejections presented in this office action.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 25, 55-58 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pullen et al. (Biochemistry, Vol. 37, No. 34, 1998) as evidenced by Uniprot P25942 intracellular domain sequence presented above.
The disclosure of Pullen provides structural investigation of the binding of TRAF-6 and TRAF-1, TRAF-2 and TRAF-3 factors to the human CD40 intracellular signalling domains (abstract). As in figure 6 for instance, TRAF6 and TRAF2 intracellular domains (PQEINF, PVQET respectively) are disclosed and are identical to variants of Consensus A, B and C of the instantly rejected claim 25 and 55-58.
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.
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.
Claim(s) 26-34 are rejected under 35 U.S.C. 103 as being unpatentable over Thompson (US20180319862A1).
Claim 26 is concerned with a chimeric antigen receptor “CoStar” molecule which comprises extracellular binding domain which may be directed to the mesothelin antigen (MSLN). The molecule additionally comprises a transmembrane domain a first signaling domain and a second signaling domain wherein the second domain “comprises a variant CD40 “ signaling domain or fragment thereof. Applicant further describes that the variant “does not comprise SEQ ID NO: 42”. SEQ ID NO:42 appears to the examiner to be a full length chimeric receptor construct. Thus receptor construct which may not be identical to the antigen binding -transmembrane -intracellular signalling domains of the SEQ ID NO: 42 do not “comprise SEQ ID NO:42”. Claim 27 indicates that the “first” intracellular signalling domain may be derived from CD28. Claim 28 indicates that the intracellular signalling domain is “full length”. Claim 29 describes that the extracellular binding domain is linked to the transmembrane domain through a linker with claims 30 and 31 further defining the length of the linker element. Claim 32 describes that the transmembrane domain is derived from CD28 with similar claim 33 describing that the transmembrane domain comprises SEQ ID NO: 21 for example as a CD28 derived transmembrane domain. Claim 34 describes the extracellular binding domain may be a variety of moiety including “a peptide” or “an scFv” .
Regarding claim 26 the prior disclosure of Thompson describes chimeric antigen receptor molecules which may have antigen binding domains directed to the mesothelin antigen (0021) as an antigen expressed by cancer cells (tumor). Thompson describes that mesothelin antigen ligand binding domain may be linked to a spacer which joins to a transmembrane domain (0022) and an intracellular signalling domain which is derived from the signalling domains of CD40 (0006) and additional signalling domain derived from CD28 for example (0012). The intracellular signalling domain may additionally comprise the signaling domain of CD3 zeta, or may not include any additional stimulatory signaling domain in addition to the CD40 and CD28 signaling domains (0011). Also see Thompson: claims 1-29 particularly claim 16, 17, 29; and [0471] and as applied to embodiment 107-117. Significantly the disclosure of Thompson provides that CD40 derived intracellular signaling domains may be functional variants of the SEQ ID NO: 12 of 85%-99% or more sequence identity. Thus structurally the disclosure of Thompson discloses a chimeric receptor with [mesothelin antigen directed binding domain/CD28 extracellular domain/CD28 transmembrane domain/CD28 intracellular signaling domain/CD40 intracellular signaling domain]. Specifically no intracellular CD3zeta primary signalling domain is required. Therefore regarding the claims 27 and 28 the disclosure of Thompson provides for the inclusion of the “full length” intracellular signalling domain of the CD28 molecule as a component of the disclosed CAR molecules. Similarly regarding the instant claims 32 and 33 the disclosure of Thompson provides transmembrane domains derived from the human CD28 (0154) as defined by the Uniprot Accession number P10747, of which the SEQ ID NO: 21 is 100% identical to the designated transmembrane domain of the reference sequence. Regarding the instant claim 34 the disclosure of Thompson provides that extracellular antigen binding domains may be derived from scFv fragments (0155). Regarding the claims 29-31 and the composition of a “linker and/or spacer” the disclosure of Thompson provides (0155) that spacer sequences may be positioned between the antigen binding domain and transmembrane/intracellular signalling domains. The disclosure provides ranges of amino acid lengths which significantly fall within the instantly claimed ranges of 5-20 (claim 30) or 10-250 (claim 31) amino acids as for example 10-20 amino acids, or 10-200 amino acids. Spacers may have also 12 amino acid or less.
It would be obvious to utilize the instantly claimed CAR components of Thompson in a chimeric antigen receptor “Costar” as previously disclosed embodiments of chimeric receptor molecules useful in therapeutic contexts.
Claim(s) 37-39 are rejected under 35 U.S.C. 103 as being unpatentable over Thompson (US20180319862A1).
Instant claim 37 in embodiments essentially claims the sequences of “Consensus” A , B, C in the context of a cell, which may be for example an alpha beta T cell (claim 38) which inherently would co-express a “TCR”(claim 39). Regarding the claim 37 as explained above the disclosure of Thompson provides for CD40 derived intracellular signalling domains as well as functional variants thereof which may be expressed in a genetically engineered T cell for example (0003). The CD40 intracellular signalling domain comprises sequences that satisfy Consensus A, B, and/or C as indicated for claims 55-58 for instance. As explained for claims 26-34 the disclosure of Thompson therefore provides all the individual components required to construct the claimed CoStar molecule. An artisan of ordinary skill in the art would be aware of the previously presented disclosure of Thompson and would construct a “Costar” molecule as claimed for the beneficial Traf-6 mediated signalling which may provide improved cellular persistence and survival in-vivo (0004).
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 26-34, 37-39 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 36, 38, 40, 41, 42-63, 67 of copending Application No. 17361621 in view of Thompson.
Similar to the instant independent claim 26, 37 the claim 36 of the reference application provides in embodiments a chimeric costimulatory receptor which comprises an extracellular antigen binding domain to a tumor associated antigen. The transmembrane domain and first intracellular signalling domain are potentially derived from CD28 and an additional CD40 derived intracellular signalling domains. It would be obvious considering the reference claims and the additional disclosure of Thompson to provide specifically a mesothelin and/or CEA directed chimeric antigen receptor molecule which comprises a CD28 derived transmembrane, CD28 derived intracellular CD40 derived intracellular signalling domain for the beneficial purposes as disclosed by Thompson above
This is a provisional nonstatutory double patenting rejection.
Claims 26-34, 37-39 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 44-70, 73-77 of copending Application No. 17936102 in view of Thompson.
The reference claim 44 is directed to a chimeric receptor molecule which is directed to mesothelin. CD28 transmembrane domain and intracellular signalling domains are claimed in combination with CD40 intracellular signalling domains. The further disclosure of Thompson accounts for elements missing from the reference claim set for example the linker spacer molecules of instant claims 29-31.
This is a provisional nonstatutory double patenting rejection.
Claims 26-34, 37-39 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 17-20, 23-26, 66-70, 72-77 of copending Application No. 17843480 in view of Thompson.
The reference claim 1 for example describes a chimeric antigen receptor /Costar which is directed to FolR1. The transmembrane domain and first and second intracellular signalling domains are derived from the CD28 molecule and CD40 molecule respectively. Considering the disclosure of Thompson it would be obvious to substitute a mesothelin or CEA directed scFv in place of the folate receptor directed antigen binding domain of the reference patent to arrive at the instantly claimed Costar molecule/cell comprising a mesothelin directed “Costar” molecule a CD28 derived intracellular signalling domain and CD40 derived intracellular signalling domain.
This is a provisional nonstatutory double patenting rejection.
Claim 26-34, 37-39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11945876 in view of Thompson.
The reference claim 1 describes a CEA directed costimulatory antigen receptor which comprises ICOS derived transmembrane domain in combination with CD40 intracellular signalling domains. Instant claims 26-27, 26-32-33 as particular embodiments comprise a CEA directed costar molecule which is constructed from ICOS derived transmembrane-intracellular signalling domain in combination with a CD40 derived intracellular signalling domain. Reference claims 2-4 similar to instant claims 29-31 describe that the extracellular binding domain is attached to the transmembrane-intracellular signalling domains through linker of 5-20 and 10-250 amino acids. Regarding embodiments of the instant invention which utilize the CD28 transmembrane and intracellular signalling domains it would likewise be obvious considering the disclosure of Thompson as indicated above to substitute the ICOS derived transmembrane and intracellular signalling domains with that derived from CD28 as disclosed by Thompson.
Claims 26-34, 37-39 rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-13 of U.S. Patent No. 12187778.
The reference claim 1 for example describes a chimeric antigen receptor /Costar which is directed to MUC16. Transmembrane domain and first and second intracellular signalling domains are derived from the CD28 molecule and CD40 molecule respectively. Considering the disclosure of Thompson it would be obvious to substitute a mesothelin or CEA directed scFv in place of the MUC16 directed antigen binding domain of the reference patent to arrive at the instantly claimed Costar molecule/cell comprising a mesothelin directed Costar molecule. in view of Thompson.
Conclusion
Summary: No claims are allowed.
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/BRIAN HARTNETT/ Examiner, Art Unit 1644
/DANIEL E KOLKER/ Supervisory Patent Examiner, Art Unit 1644