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 .
DETAILED ACTION
Amendments
In the reply filed 11/10/2025, Applicant has amended claims 53, 55-59 and 67, newly canceled claim 66, and added new claims 70-72.
Claim Status
Claims 51-65 and 67-72 are pending.
Claims 61-65 and 68-69 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/13/2025.
Claims 51-60, 67 and 70-72 are considered on the merits.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/10/2025 and 12/19/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. The corresponding signed and initialed PTO forms 1449 have been mailed with this action.
Withdrawn Specification Objections
The prior objection to the disclosure because of an embedded hyperlink is withdrawn in light of Applicant’s amendment to remove the hyperlink.
Withdrawn Claim Objections
The prior objection to claims 58-59 and 67 because of minor informalities is withdrawn in light of Applicant’s amendments to the claims.
Withdrawn Claim Rejections - 35 USC § 112
The prior rejection of claims 53, 57 and 67 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for reciting a subjective term or for lack of antecedent basis, is withdrawn in light of Applicant’s amendment to the claims.
Withdrawn Claim Rejections - 35 USC § 112(a)
The prior rejection of claims 55 and 56 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of Applicant’s amendment to the claims.
Withdrawn Claim Rejections - 35 USC § 102
The prior rejection of claim 67 under 35 U.S.C. 102 (a)(1) as being anticipated by Hust et al (WO 2018/001874. Cited in IDS 05/30/2023) is withdrawn in light of Applicant’s changing its dependency from claim 60 that is not anticipated by Hust.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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.
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.
Claims 51-55, 57, 59-60, 67 and 70-71 are rejected under 35 U.S.C. 103 as being unpatentable over Hust et al (WO 2018/001874. Published January 2018. Cited in IDS 05/30/2023).
It is noted that the prior rejection of claims 51-55, 57 and 59-60 is maintained. The following changes are to address the amended claim 67 and new claims 70-71.
With respect to claim 51, Hust teaches a vector comprising a nucleic acid sequence encoding a HLA-specific CAR (“CAR-A*02”, see e.g., abstract and p. 5, last para and p. 4, para 1) and a nucleic acid sequence encoding a FOXP3 (p. 4, para 2), and teaches expression of FOXP3 with the fusion protein CAR-A*02 can be linked by expression of a fusion of P2A and can be from one unified mRNA (p. 4, last para). Thus, Hust teaches a vector (see e.g., Fig 5 and Fig 1) comprising a first polynucleotide encoding a FOXP3 polypeptide and a second polynucleotide encoding a CAR that specifically binds to an HLA, wherein the first and the second polynucleotides are operably linked to the same promoter.
However, Hust teaches an exemplary fusion protein of CAR-P2A-FOXP3 (p. 4, last para), in which the polynucleotide encoding the FOXP3 (equivalent to the first polynucleotide) is downstream of the HLA-CAR (equivalent to the second polynucleotide), but does not specifically teach an example of the polynucleotide encoding the FOXP3 being upstream of that encoding the CAR.
Nevertheless, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have chosen the order of the two polynucleotides so as to place the polynucleotide encoding the FOXP3 (i.e., the first polynucleotide) upstream of the polynucleotide encoding the CAR (i.e., the second polynucleotide) with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to choose this order because it is a simple reversal of parts (i.e., reversal of the two polynucleotides), and it has been held that mere reversal of parts is an obvious modification. See MPEP 2144.04 (VI) (A).
With respect to claim 52 directed to the antigen recognition domain specifically binding to HLA-A2, Hust teaches the CAR-A*02 contains an scFv domain that is specific for the human HLA-A*02 (p. 4, para 1).
With respect to claim 53 directed to the vector comprising a self-cleaving sequence P2A between the first polynucleotide and the second polynucleotide, as stated supra, Hust teaches a fusion protein of CAR-P2A-FOXP3 (p. 4, last para) in which the CAR and the FOXP3 is linked by a P2A, thus teaches the vector comprises a self-cleaving sequence P2A between the polypeptides (see e.g., Fig 5).
With respect to claim 54 directed to (a) the FOXP3 polypeptide comprising an amino acid sequence having 100% identity to SEQ ID NO: 1, Hust teaches the human FOXP3 polypeptide comprises an amino acid sequence of Hust SEQ ID NO: 22 (see p. 4, last line – p. 5, line 1), which comprises an amino acid sequence that is 100% identical to the instant SEQ ID NO: 1 (see below).
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With respect to claim 55 directed to the antigen recognition domain being a single chain antibody (scFv), as stated supra, Hust teaches the CAR-A*02 contains an scFv domain that is specific for the human HLA-A*02 (p. 4, para 1).
With respect to claim 57 (f) directed to the CAR comprising a CD8 hinge domain, a CD8 transmembrane domain, a CD28 signaling domain and a CD3 zeta signaling domain, Hust teaches the CAR-A*02 comprises a CD8 hinge and CD8 transmembrane domain, a CD28 signaling domain and a CD3 zeta signaling domain (see e.g., p. 5, para 2 and Fig 1).
With respect to claim 59 directed to an engineered T cell comprising the vector and claim 60 directed to an engineered regulatory T cell (Treg), as stated supra, Hust teaches a regulatory T cell (Treg) that is transduced with the vector comprising the nucleic acid sequence encoding the HLA-specific CAR and the FOXP3 (e.g., abstract, p. 5, last para and p. 4, para 1-2).
With respect to claim 67 directed to a pharmaceutical composition comprising the engineered Treg, Hust teaches the human Treg cell expressing the CAR-A *02 is a pharmaceutical compound for the treatment of HvG disease (p. 4, para 1), thus teaches a pharmaceutical composition comprising the engineered Treg.
With respect to claim 70 directed to the vector comprising a self-cleaving sequence P2A between the first polynucleotide and the second polynucleotide, as stated supra, Hust teaches a fusion protein of CAR-P2A-FOXP3 (p. 4, last para) in which the CAR and the FOXP3 is linked by a P2A, thus teaches the vector comprises a self-cleaving sequence P2A between the polynucleotides (see e.g., Fig 5).
With respect to claim 71 directed to the CAR comprising a hinge, transmembrane domain or signaling domains, as stated supra, Hust teaches the CAR-A*02 comprises a CD8 hinge and CD8 transmembrane domain, a CD28 signaling domain and a CD3 zeta signaling domain (see e.g., p. 5, para 2 and Fig 1).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 11/10/2025 are acknowledged.
Applicant argues that based on the disclosure of Hust, it would not have been obvious to reverse the order of FOXP3 and CAR within the vector because Hust indicates the expression of CAR is of primary importance while FOXP3 is an optional possibility. Thus one of ordinary skill in the art would not have been motivated to reorder the genes. And it would be apparent to one ordinary skill in the art to use general common knowledge to position the CAR upstream of an accessory gene such as FOXP3 (Remarks, p. 19-20).
Applicant’s arguments have been fully considered but they are not persuasive.
As a first matter, in response to the argument that the FOXP3 is an optional possibility and an accessory gene, the MPEP 2123 (I) states that patents are relevant as prior art for all they contain, and that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. In instant case, Hust teaches FOXP3 fused to a CAR in “Description of the invention” (see p. 4) and in a working example (see e.g., Example 4 and Fig 5a), demonstrates FOXP3 expression in Fig 5d, and recites FOXP3 in Hust claim 12. Therefore, Hust clearly teaches and reduces to practice FOXP3.
Furthermore, with respect to the order of CAR and FOXP3, it is noted that although Hust teaches an exemplary fusion protein of CAR-P2A-FOXP3 (p. 4, last para) with CAR being upstream of FOXP3, Hust does not dissuade one of ordinary skill in the art from reordering the two molecules so as to place FOXP3 upstream of CAR. Hust teaches “Such a fusion, e.g. encoded by one expression cassette adapted to generate one unified mRNA encoding the fusion protein of CAR-P2A-FOXP3, would yield free FOXP3 by its hydrolysis from the P2A domain” (p. 4, last para, see CAR and FOXP3 expression in Fig 5c-5d), thus teaches the fusion protein, of CAR and FOXP3 linked by a P2A, would undergo hydrolysis to yield free CAR and free FOXP3. Therefore, one of ordinary skill in the art would have had a reason to choose either of the two orders to obtain the same results (i.e., to yield free CAR and free FOXP3).
Applicant further argues that inserting FOXP3 upstream of CAR provides a phenotype lock to ensure that expression of the CAR without the FOXP3 does not occur, and the presence of FOXP3 expression prevents Treg cells from acquiring an effector phenotype. These features provide Treg cells with safety characteristics that are not disclosed in Hust. Specifically, Treg cells without FOXP3 in vector demonstrate suppressed immune response under proinflammatory conditions and loss of their FOXP3 phenotype (see Figs 1-3 in Remarks, p. 20-22).
Applicant’s arguments have been fully considered but they are not persuasive.
As a first matter, the feature of phenotype lock, that the Treg cells do not acquire an effector phenotype, is due to expression of FOXP3 (see Figs 1-3 in Remarks comparing Treg cells with and without FOXP3 transduction), but is not due to inserting FOXP3 upstream of CAR. In other words, Hust’s exemplary vector of CAR-P2A-FOXP3 that leads to FOXP3 expression (see Hust Fig 5d) would have had the same feature of phenotype lock to the transduced Treg cells.
Secondly, in regard to the safety characteristic that ensure that expression of the CAR without the FOXP3 does not occur, as stated supra, Hust teaches “Such a fusion, e.g. encoded by one expression cassette adapted to generate one unified mRNA encoding the fusion protein of CAR-P2A-FOXP3, would yield free FOXP3 by its hydrolysis from the P2A domain” (p. 4, last para, see CAR and FOXP3 expression in Fig 5c-5d), thus teaches the vector comprising a P2A sequence would have ensured generating one unified mRNA that would yield free FOXP3 and free CAR by the hydrolysis from the P2A domain, and thus would have ensured that expression of the CAR without the FOXP3 does not occur.
In regard to the argument that these features are not disclosed in Hust, it is noted that there is no requirement that a person of ordinary skill in the art would have recognized the natural disclosure at the time of invention, but only that the subject matter is in fact naturally present in the prior art reference. See MPEP 2112 II. In the instant case, as stated supra, these features of phenotype lock and safety characteristic are due to FOXP3 expression and the hydrolysis of the P2A domain, and thus are naturally present in the vector taught by Hust.
Therefore, Applicant’s arguments are not persuasive, and the prior rejection under 103 is maintained.
Claim 56 stands rejected under 35 U.S.C. 103 as being unpatentable over Hust et al (WO 2018/001874. Published January 2018. Cited in IDS 05/30/2023) in view of NCBI alignment (comparison of HLA-A2 antibody clone 3PB2 with instant SEQ ID NOs 8-10 and 20-22. Sequences posted in 2001. P. 1-3. Prior art of record).
Claim 56 is directed to the antigen recognition domain comprising a variable heavy domain comprising CDR1-3 comprising SEQ ID NOs: 8-10 and a variable light domain comprising CDR1-3 comprising SEQ ID NOs: 20-22.
In regard to the sequence of the antigen recognition domain, Hust teaches the scFv domains for the CAR-A*02 were generated by affinity selection for HLA-A*02 using a phage display library expressing an anti-HLA-A*02 antibody. The anti-HLA-A*02 (nucleotide sequences accessible at EBI for heavy chain: AF163303; light chain: AF163304) was cloned from a patient who had developed A*02 reactive antibodies subsequent to blood transfusion (see Example 1, p. 8, last para). Thus, Hust teaches an anti-HLA-A*02 antibody comprising sequences from accession numbers AF163303 and AF163304 that is cloned from a patient.
NCBI alignment of AF163303 with SEQ ID NO: 8, 9 and 10 and AF163304 with SEQ ID NO: 20, 21 and 22 has been attached. NCBI alignment demonstrates that the anti-HLA-A2 antibody clone 3PB2 has a heavy chain variable region AF163303 that comprises instant SEQ ID NOs: 8, 9 and 10, and has a light chain variable region AF163304 that comprises instant SEQ ID NOs: 20, 21 and 22 (see page 1 of the file).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have chosen the scFv of the HLA-CAR comprising a heavy chain variable region AF163303 and a light chain variable region AF163304 which comprise the instant SEQ ID NOs: 8, 9 and 10 and instant SEQ ID NOs: 20, 21 and 22, respectively, as suggested by Hust in view of NCBI alignment with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to choose these sequences because Hust teaches the sequence of the anti-HLA-A2 antibody is cloned from a human patient and is reactive to HLA-A2 antigen.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 11/10/2025 are acknowledged and have been discussed above.
Claims 54 and 58 stand rejected under 35 U.S.C. 103 as being unpatentable over Hust et al (WO 2018/001874. Published January 2018. Cited in IDS 05/30/2023) in view of ENA FOXP3 sequence (ENA accession NO: EF534714, uploaded in 2007, p. 1-3. Prior art of record) and Cooper et al., (US 2017/0183407 A1, prior art of record).
Claims 54 and 58 are directed to the first polynucleotide comprising SEQ ID NO: 3 and the second polynucleotide comprising at least 70% identity to SEQ ID NO: 211.
As stated supra, Hust teaches the vector comprises a nucleic acid sequence encoding human FOXP3 (p. 4, para 2). Hust teaches the CAR-A*02 comprises a CD8 hinge and CD8 transmembrane domain, a CD28 signaling domain and a CD3 zeta domain with respective amino acid sequences (see e.g., p. 5, para 2 and Fig 1).
However, Hust is silent on the polynucleotide sequence encoding human FOXP3 comprising SEQ ID NO: 3, nor teach the polynucleotide sequence encoding the hinge, transmembrane domain and intracellular domains of the CAR comprising at least 70% identity to SEQ ID NO: 211 in claims 54 and 58.
In regard to the polynucleotide sequence encoding human FOXP3, European Nucleotide Archive (ENA) discloses human FOXP3 cDNA sequence that is uploaded in 2007 (see ENA file attached, p. 3). The cDNA sequence of human FOXP3 in ENA with accession number EF534714 is 100% identical to the instant SEQ ID NO: 3 in claims 54 and 58 (see SCORE search 07/15/2025, -3.rge file, Result #1).
In regard to the polynucleotide sequence encoding the CD8 hinge and CD8 transmembrane domain, the CD28 signaling domain and the CD3 zeta signaling domain of the CAR, Cooper teaches a CAR construct (CAR213 having the sequence of Cooper SEQ ID NO: 5) comprising a CD8 hinge and CD8 transmembrane domain, a CD28 signaling domain and a CD3 zeta signaling domain (see e.g., Fig 3 for the elements in the CAR213). The sequence of Cooper SEQ ID NO: 5 comprises a sequence that is 87% identical to the instant SEQ ID NO: 211 in claims 54 and 58 (see SCORE search 07/15/2025, -211.rni file, Result #29).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the vector comprising a polynucleotide encoding human FOXP3 and a polynucleotide encoding a CD8 hinge and CD8 transmembrane domain, a CD28 signaling domain and a CD3 zeta signaling domain of the CAR disclosed by Hust, by choosing the cDNA sequence of human FOXP3 taught by ENA (Accession NO: EF534714) and choosing the polynucleotide sequence encoding the CAR construct as taught by Cooper with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to choose the sequences since ENA and Cooper have reduced to practice the sequences encoding human FOXP3 and encoding a CAR construct. Furthermore, the successful cloning and sequencing of the cDNA encoding a known protein (FOXP3) is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the cDNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art. Ex parte Kubin, 83 U.S.P.Q.2d (BNA) 1410 (B.P.A.I. 2007), aff'd, 561 F.3d 1351 (Fed. Cir. 2009).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 11/10/2025 are acknowledged and have been discussed above.
Claim 72 is rejected under 35 U.S.C. 103 as being unpatentable over Hust et al (WO 2018/001874. Cited in IDS 05/30/2023) in view of ENA FOXP3 sequence (ENA accession NO: EF534714, uploaded in 2007, p. 1-3. Prior art of record) and Cooper et al., (US 2017/0183407 A1, prior art of record), as applied to claim 58 and claim 51 above, and further in view of Kim et al., (PLoS ONE. 2011; 6(4): e18556, p. 1-8).
Claim 72 is directed to the first polynucleotide comprising a self-cleaving sequence which has at least 70% identity to SEQ ID NO: 214.
As stated supra, Hust teaches a fusion protein of CAR-P2A-FOXP3 (p. 4, last para) in which the CAR and the FOXP3 is linked by a P2A (e.g., Fig 5), thus makes obvious the first polynucleotide comprising a self-cleaving sequence P2A.
However, Hust, ENA and Cooper are silent on the P2A comprising a sequence which has at least 70% identity to SEQ ID NO: 214.
Kim teaches the nucleotide sequence that encodes a P2A (see e.g. Fig 1B). The nucleotide sequence of Kim has at least 70% identity to SEQ ID NO: 214 (see below).
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Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the vector comprising the first polynucleotide comprising a self-cleaving sequence P2A as suggested by Hust in view of ENA and Cooper, by choosing a nucleotide sequence of P2A that has at least 70% identity to SEQ ID NO: 214 as taught by Kim with a reasonable expectation of success. Since Kim aims to generate 2A-harboring cloning vectors to help biomedical researchers easily adopt the 2A technology for bicistronic expression (e.g., abstract) and reduces to practice the nucleotide sequence of P2A, one of ordinary skill in the art would have had a reason to choose the nucleotide sequence of P2A as taught by Kim. Furthermore, the successful cloning and sequencing of the cDNA encoding a known protein (P2A) is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the cDNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 11/10/2025 are acknowledged and have been discussed above.
Maintained Provisional Double Patenting Rejections
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 51-57, 59-60, 67 and 70-71 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending claims 1-2, 9, 18, 21, 23-24 and 27-28 of copending Application No. 18/042,927 (‘927). Although the claims at issue are not identical, they are not patentably distinct from each other.
Copending claims recite a vector comprising three nucleotide sequences, in which the second sequence encodes FOXP3 (equivalent to the instant first sequence), and the third sequence encodes a CAR (equivalent to the instant second sequence), the sequences are operably linked to an SFFV promoter, the FOXP3 sequence is upstream of the CAR sequence (reference claim 1), the sequences are separated by nucleotide sequence encoding self-cleavage sequence which are 2A sequence (reference claim 2), the FOXP3 is a polypeptide comprising an amino acid sequence of SEQ ID NO: 2 (which is 100% identical to the instant SEQ ID NO: 1), the CAR is directed against HLA-A2, the antigen binding domain comprises VH CDR 1, 2 and 3 as set forth in SEQ ID NOs: 11, 12 and 13 (which are 100% identical to the instant SEQ ID NOs: 8, 9 and 10), and VL CDR1, 2 and 3 as set forth in SEQ ID NOs: 14, 15 and 16 (which are 100% identical to the instant SEQ ID NOs: 20, 21 and 22) (reference claim 9), the CAR comprises a CD8 hinge and transmembrane domain, a CD28 co-stimulatory domain and a CD3 zeta signaling domain (reference claim 18), the vector is a viral vector (reference claim 21), a cell comprising the vector (reference claim 23), the cell is a Treg (reference claim 24), a cell population of the cell (reference claim 27) and a pharmaceutical composition comprising the cell population (reference claim 28).
It is clear that elements of the cited application claims are to be found in instant claims. The difference between the cited application claims and the instant claims lies in the fact that the cited application claims are much more specific (e.g., with three sequences). Thus the invention of said claims of the cited application are in effect “species” of the “generic” invention of the instant claim. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Since the instant application claims are anticipated by cited application claims, said claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims in the copending application have not in fact been patented.
Claim 58 and 72 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending claims 1-2, 9, 18, 21, 23-24, 27-28 of copending Application No. 18/042,927 (‘927) in view of ENA FOXP3 sequence (ENA accession NO: EF534714, uploaded in 2007, p. 1-3. Prior art of record), Cooper et al., (US 2017/0183407 A1. Prior art of record) and Kim et al., (PLoS ONE. 2011; 6(4): e18556, p. 1-8). Although the claims at issue are not identical, they are not patentably distinct from each other.
However, copending claims are silent on the polynucleotide sequences encoding the human FOXP3 or the CAR in claim 58, or the first polynucleotide comprising a self-cleaving sequence which has at least 70% identity to SEQ ID NO: 214 in claim 72.
In regard to the polynucleotide sequence encoding human FOXP3, European Nucleotide Archive (ENA) discloses human FOXP3 cDNA sequence that is uploaded in 2007 (see ENA file attached, p. 3). The cDNA sequence of human FOXP3 in ENA with accession number EF534714 is 100% identical to the instant SEQ ID NO: 3 in claim 58 (see SCORE search 07/15/2025, -3.rge file, Result #1).
In regard to the polynucleotide sequence encoding the CD8 hinge and CD8 transmembrane domain, the CD28 signaling domain and the CD3 zeta signaling domain of the CAR, Cooper teaches a CAR construct (CAR213 having the sequence of Cooper SEQ ID NO: 5) comprising a CD8 hinge and CD8 transmembrane domain, a CD28 signaling domain and a CD3 zeta signaling domain (see e.g., Fig 3 for the elements in the CAR213). The sequence of Cooper SEQ ID NO: 5 comprises a sequence that is 87% identical to the instant SEQ ID NO: 211 in claim 58 (see SCORE search 07/15/2025, -211.rni file, Result #29).
In regard to the P2A sequence, Kim teaches the nucleotide sequence encoding a P2A (see e.g. Fig 1B) that has at least 70% identity to SEQ ID NO: 214 (see above).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the vector comprising a polynucleotide encoding human FOXP3 and a polynucleotide encoding a CD8 hinge and CD8 transmembrane domain, a CD28 signaling domain and a CD3 zeta signaling domain of the CAR, and a 2A sequence recited by the copending claims, by choosing the cDNA sequence of human FOXP3 taught by ENA (Accession NO: EF534714), choosing the polynucleotide sequence encoding the CAR construct as taught by Cooper and choosing the nucleotide sequence encoding a P2A that has at least 70% identity to SEQ ID NO: 214 as taught by Kim with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to choose the sequences since ENA, Cooper and Kim have reduced to practice the sequences encoding human FOXP3 and encoding a CAR construct and a P2A domain. Furthermore, the successful cloning and sequencing of the cDNA encoding a known protein (i.e., FOXP3 or P2A) is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the cDNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art.
Since the instant application claims are obvious over cited application claims, in view of ENA, Cooper and Kim, said claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims in the copending application have not in fact been patented.
Response to Traversal:
Applicant’s arguments filed on 11/10/2025 are acknowledged.
Applicant requests that the double patenting rejections be held in abeyance until allowable subject matter is identified. This is not found persuasive therefore the rejections are maintained. Applicant is reminded that a complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims, or the filing of a terminal disclaimer. Such a response is required even when the nonstatutory double patenting rejection is provisional. See MPEP 804.I.B.1.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jianjian Zhu whose telephone number is (571)272-0956. The examiner can normally be reached M - F 8:30AM - 4PM (EST).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Douglas (Doug) Schultz can be reached on (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JIANJIAN ZHU/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631