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 .
Status of Application, Amendments and/or Claims
The amendments of 12 July 2024 and 07 November 2023 have been entered in full. Claims 4-7, 11-15 are amended. Claims 16 and 17 are added.
Claims 1-17 are under consideration in the instant application.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12 July 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
1. The drawings are objected to because Figures 1-6, 7A, 7B, and 8 contain views that have an incorrect orientation. References characters, sheet numbers, and view numbers must be oriented in the same direction as the view so as to avoid having to rotate the sheet (see 37 CFR 1.84(p)(1)).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
2. Specific deficiencies and the required response to this Office Action are as follows:
2a. Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Please see page 1, line 15; page 3, lines 20-21; page 5, line 26; and page 34, line 8.
2b. Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
3. Claims 1, 2, 8, and 9 are objected to because of the following informalities:
3a. Claim 1 recites the acronym “PRAME” without first defining what it represents. While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym and/or in each independent claim.
3b. In claim 2, line 1, the phrase “is capable of binding” should be simplified to recite “binds”.
3c. In claim 8, lines 2 and 3, after each recitation of the word “encoding”, the word “the” is missing and should be inserted.
3d. In claim 9, lines 2 and 3, after each recitation of the word “encoding”, the word “the” is missing and should be inserted.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
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 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.
4. Claims 1-17 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (US 2019/0247432; cited on the IDS of 12 July 2024) and Weis et al. (WO 2021/099360; priority to 18 November 2019; cited on the IDS of 12 July 2024).
Zhao et al. teach a genetically modified immune cell (i.e., T cell) comprising (i) an exogenous T cell receptor having affinity for NY-ESO-1 and (ii) a switch receptor (page 1, [0008-0011]; page 2, [0030]; Example 5; page 27, [0303]). Zhao et al. disclose that the T cell receptor having affinity for NY-ESO-1 comprises a TCR alpha chain and a TCR beta chain (page 2, [0028]). Zhao et al. also indicate that the switch receptor comprises a first domain comprising at least a portion of the extracellular domain of PD1; a second domain comprising a switch receptor transmembrane domain comprising at least a portion of the transmembrane domain of CD8alpha; and a third domain comprising at least a portion of the intracellular domain of 4-1BB, meeting the limitations of instant claim 1 (page 3, [0040]; pages 19-20, [0258-0259]). Zhao et al. teach that the PD1-41BB switch receptor (PD1.BB) comprises the amino acid sequence of SEQ ID NO: 134 (page 19, [0258]). It is noted that amino acids 1-170 of SEQ ID NO: 134 of Zhao et al. are 100% identical to the PD-1 extracellular domain sequence of SEQ ID NO: 28, as required by instant claim 6 (see sequence alignment below).
Qy= instant SEQ ID NO: 28
Db= SEQ ID NO: 134 of Zhao et al.
RESULT 1
US-16-216-774-134
Query Match 100.0%; Score 921; DB 1; Length 237;
Best Local Similarity 100.0%;
Matches 170; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MQIPQAPWPVVWAVLQLGWRPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTS 60
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MQIPQAPWPVVWAVLQLGWRPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTS 60
Qy 61 ESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGT 120
Qy 121 YLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLV 170
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 YLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLV 170
Furthermore, amino acids 196-237 of SEQ ID NO: 134 of Zhao et al. are 100% identical to the 4-1BB intracellular domain sequence of SEQ ID NO: 32, as required by instant claim 6 (see sequence alignment below).
Qy= instant SEQ ID NO: 32
Db= SEQ ID NO: 134 of Zhao et al.
RESULT 1
US-16-216-774-134
Query Match 100.0%; Score 232; DB 1; Length 237;
Best Local Similarity 100.0%;
Matches 42; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL 42
||||||||||||||||||||||||||||||||||||||||||
Db 196 KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL 237
Zhao et al. teach nucleic acids encoding the exogenous TCR and switch receptor (and vectors comprising such) (page 23, [0271-0273]; pages 25-26, [0290-0294]). Zhao et al. indicate immune cells to be modified may be obtained from peripheral blood mononuclear cells or peripheral blood lymphocytes, meeting the limitations of instant claim 12 (pages 39-40, [0388-0389], [0392]).
Zhao et al. disclose pharmaceutical compositions comprising the modified cells, meeting the limitations of instant claim 13 (page 44, [0422]; page 49, [0465-0466]). Zhao et al. state that the modified cells may be administered to treat cancer in a human or non-human animal, meeting the limitations of instant claims 14-17 (page 10, [0208]; page 44, [0425-0427]; pages 45-46, [0433-0438]). Zhao et al. teach that high affinity PD1 switch receptors enhance NY-ESO-1 TCR anti-tumor activity (Examples 2-5).
Zhao et al. do not teach a cell comprising a PRAME specific T cell receptor (TCR) comprising a TCR α chain comprising a CDR1 having the amino acid sequence of SEQ ID NO: 2, a CDR2 having the amino acid sequence of SEQ ID NO: 3, and a CDR3 having the amino acid sequence of SEQ ID NO: 4; and a TCR β chain comprising a CDR1 having the amino acid sequence of SEQ ID NO: 5, a CDR2 having the amino acid sequence of SEQ ID NO: 6, and a CDR3 having the amino acid sequence of SEQ ID NO: 7.
Weis et al. teach a host cell comprising a PRAME TCR that specifically recognizes the PRAME amino acid sequence, SLLQHLIGL, or its HLA-A2 bound form (including HLA-A*02:01, HLA-A*02:02 or HLA-A*02:04), meeting the limitations of instant claims 1-3 (pages 2-3, [006-010]; page 5, [0024]). Weis et al. state that the host cell may be a peripheral blood lymphocyte, peripheral blood mononuclear cell, or T cell, among others, meeting the limitations of instant claim 12 (page 5, [0024]; page 19, [0077]). Weis et al. disclose that the PRAME TCR comprises a TCR α chain comprising a CDR1 having the amino acid sequence of SEQ ID NO: 2, a CDR2 having the amino acid sequence of SEQ ID NO: 4, and a CDR3 having the amino acid sequence of SEQ ID NO: 6; and a TCR β chain comprising a CDR1 having the amino acid sequence of SEQ ID NO: 3, a CDR2 having the amino acid sequence of SEQ ID NO: 5, and a CDR3 having the amino acid sequence of SEQ ID NO: 7 (page 3, [008]; page 4, [0012]).
It is noted that the Weis et al. TCR α chain CDR1 sequence of SEQ ID NO: 2 is 100% identical to the instant amino acid sequence of SEQ ID NO: 2 (SIFNT) (see page 30 of Weis et al.).
The Weis et al. TCR α chain CDR2 sequence of SEQ ID NO: 4 is 100% identical to the instant amino acid sequence of SEQ ID NO: 3 (LYKAGEL) (see page 30 of Weis et al.).
The Weis et al. TCR α chain CDR3 sequence of SEQ ID NO: 7 is 100% identical to the instant amino acid sequence of SEQ ID NO: 4 (CAGLADYGGSQGNLIF) (see page 30 of Weis et al.).
The Weis et al. TCR β chain CDR1 sequence of SEQ ID NO: 3 is 100% identical to the instant amino acid sequence of SEQ ID NO: 5 (SGDLS) (see page 30 of Weis et al.).
The Weis et al. TCR β chain CDR2 sequence of SEQ ID NO: 5 is 100% identical to the instant amino acid sequence of SEQ ID NO: 6 (YYNGEE) (see page 30 of Weis et al.).
The Weis et al. TCR β chain CDR3 sequence of SEQ ID NO: 7 is 100% identical to the instant amino acid sequence of SEQ ID NO: 7 (CASSVWASGGYEQYF) (see page 30 of Weis et al.).
Furthermore, the Weis et al. variable TCR α and β chain amino acid sequences of SEQ ID NO: 10 and 11 are 100% identical to the TCR α and β chain amino acid sequences of SEQ ID NO: 8 and 9 of the instant application, meeting the limitations of instant claim 4 (Weis et al., page 4, [0013]; see sequence alignments, below).
Qy= instant SEQ ID NO: 8
Db= SEQ ID NO: 10 of Weis et al.
ID BJK27227 standard; protein; 273 AA.
DE TCR alpha chain variable region polypeptide SEQ: 10.
XX
KW T cell receptor alpha chain; TCR alpha chain; cancer; cytostatic;
KW diagnostic test; t-lymphocyte.
CC PN WO2021099360-A1.
XX
CC PD 27-MAY-2021.
XX
CC PF 18-NOV-2020; 2020WO-EP082488.
XX
PR 18-NOV-2019; 2019EP-00209757.
XX
CC PA (MEDI-) MEDIGENE IMMUNOTHERAPIES GMBH.
XX
CC PI Weis M, Kehler P, Gerget M, Krendl C, Wilde S;
XX
SQ Sequence 273 AA;
Query Match 100.0%; Score 698; Length 273;
Best Local Similarity 100.0%;
Matches 133; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MLLEHLLIILWMQLTWVSGQQLNQSPQSMFIQEGEDVSMNCTSSSIFNTWLWYKQDPGEG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MLLEHLLIILWMQLTWVSGQQLNQSPQSMFIQEGEDVSMNCTSSSIFNTWLWYKQDPGEG 60
Qy 61 PVLLIALYKAGELTSNGRLTAQFGITRKDSFLNISASIPSDVGIYFCAGLADYGGSQGNL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PVLLIALYKAGELTSNGRLTAQFGITRKDSFLNISASIPSDVGIYFCAGLADYGGSQGNL 120
Qy 121 IFGKGTKLSVKPN 133
|||||||||||||
Db 121 IFGKGTKLSVKPN 133
Qy= instant SEQ ID NO: 9
Db= SEQ ID NO: 11 of Weis et al.
AC BJK27228;
DE TCR beta chain variable region polypeptide SEQ: 11.
XX
KW T cell receptor alpha chain; TCR alpha chain; cancer; cytostatic;
KW diagnostic test; t-lymphocyte.
XX
CC PN WO2021099360-A1.
XX
CC PD 27-MAY-2021.
XX
CC PF 18-NOV-2020; 2020WO-EP082488.
XX
PR 18-NOV-2019; 2019EP-00209757.
XX
CC PA (MEDI-) MEDIGENE IMMUNOTHERAPIES GMBH.
XX
CC PI Weis M, Kehler P, Gerget M, Krendl C, Wilde S;
XX
CC PS Claim 7; SEQ ID NO 11; 95pp; English.
XX
SQ Sequence 312 AA;
Query Match 100.0%; Score 707; Length 312;
Best Local Similarity 100.0%;
Matches 133; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MGFRLLCCVAFCLLGAGPVDSGVTQTPKHLITATGQRVTLRCSPRSGDLSVYWYQQSLDQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MGFRLLCCVAFCLLGAGPVDSGVTQTPKHLITATGQRVTLRCSPRSGDLSVYWYQQSLDQ 60
Qy 61 GLQFLIQYYNGEERAKGNILERFSAQQFPDLHSELNLSSLELGDSALYFCASSVWASGGY 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLQFLIQYYNGEERAKGNILERFSAQQFPDLHSELNLSSLELGDSALYFCASSVWASGGY 120
Qy 121 EQYFGPGTRLTVT 133
|||||||||||||
Db 121 EQYFGPGTRLTVT 133
Furthermore, the Weis et al. constant TCR α and β region amino acid sequences of SEQ ID NO: 29 and 30 are 100% identical to the constant TCR α and β region amino acid sequences of SEQ ID NO: 10 and 11, respectively, of the instant application, meeting the limitations of instant claim 5 (Weis et al., page 4, [0014-0015]; page 16, [0067-0068]).
Weis et al. teach nucleic acids encoding the TCR, vectors, and host cells (including lymphocytes) and pharmaceutical compositions comprising such (page 5, [0021-0026]; pages 29-41). Weis et al. also disclose that the TCR, nucleic acids, or host cells may be administered for the treatment of cancer (pages 6-7, [0028-0031]; page 45, [00168-00170]).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to modify the immune cell comprising (i) an exogenous T cell receptor (TCR) having affinity for NY-ESO-1 and (ii) a switch receptor comprising an extracellular domain of PD1, a transmembrane domain, and the intracellular domain of 4-1BB as taught by Zhao et al. by substituting the NY-ESO-1-specific TCR sequences of Zhao et al. for the PRAME-specific TCR sequences as taught by Weis et al. The person of ordinary skill in the art would have been motivated to make that modification because PRAME, like NY-ESO-1 is a tumor-associated antigen expressed in a wide variety of tumors and the PRAME-specific TCR is suitable for adoptive T cell therapy (see Weis et al., page 2, [005]; page 10, [0048]; pages 52-53, Example 4). Furthermore, the skilled artisan would be motived to include the PRAME-specific TCR in a cell with a switch receptor comprising an extracellular domain of PD-1 because the modified cell would counteract the upregulation and/or expression of inhibitory receptors and/or ligands that can negatively control T cell activation and T cell function (Zhao et al., page 7, [0164]). Zhao et al. disclose, for example, that expression of certain immune checkpoint proteins (i.e., PD-1 and its ligands PD-L1) on T cells and/or in the tumor microenvironment can reduce the potency and efficacy of adoptive T cell therapy (page 7, [0164]). Therefore, the modified immune cells comprising a TCR and switch receptor comprising an extracellular domain of PD-1 address T cell exhaustion and/or the lack of T cell persistence that is a barrier to the efficacy and therapeutic outcomes of conventional adoptive cell therapies (Zhao et al., pages 7-8, [0164]). The person of ordinary skill in the art reasonably would have expected success because the inclusion of a switch receptor in TCR-modified immune cells successfully enhances the function of the immune cells in a tumor microenvironment (see Zhao et al.; pages 56-58, Examples 2-5). Therefore, the claimed invention as a whole was clearly prima facie obvious over the prior art.
It is noted to Applicant that the applied Weis et al. reference has a common applicant and inventor (Wilde) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
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.
5. Claims 1-3, 6, 7, and 11-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27, 29, 31, 48-55 of copending Application No. 18/686,664. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims recite a cell comprising (A) a PRAME specific T cell receptor and (B) a chimeric co-stimulatory receptor.
Claim 1 of the instant application is directed to a cell comprising
(A) a PRAME specific T cell receptor (TCR) comprising a TCR α chain comprising a CDR1 having the amino acid sequence of SEQ ID NO: 2, a CDR2 having the amino acid sequence of SEQ ID NO: 3, and a CDR3 having the amino acid sequence of SEQ ID NO: 4; and a TCR β chain comprising a CDR1 having the amino acid sequence of SEQ ID NO: 5, a CDR2 having the amino acid sequence of SEQ ID NO: 6, and a CDR3 having the amino acid sequence of SEQ ID NO: 7; and
(B) a chimeric co-stimulatory receptor containing an extracellular domain containing an extracellular domain derived from PD-1, a transmembrane domain, and an intracellular domain containing an intracellular domain derived from 4-1BB.
Meanwhile, claim 27 of the ‘664 application recites a target specific immune cell expressing (A) an antigen specific T cell receptor (TCR), and (B) a chimeric co-stimulatory receptor, wherein the chimeric co-stimulatory receptor comprises an extracellular domain containing a polypeptide derived from PD-1, a transmembrane domain, and an intracellular domain containing a polypeptide derived from 4-1BB, wherein the target specific immune cell secretes at least two proteins.
Claim 31 of the ‘664 application recites that the target specific immune cell expresses
(A) a PRAME specific T cell receptor (TCR) comprising a TCR α chain comprising a CDR1 having the amino acid sequence of SEQ ID NO: 2, a CDR2 having the amino acid sequence of SEQ ID NO: 3, and a CDR3 having the amino acid sequence of SEQ ID NO: 4; and a TCR β chain comprising a CDR1 having the amino acid sequence of SEQ ID NO: 5, a CDR2 having the amino acid sequence of SEQ ID NO: 6, and a CDR3 having the amino acid sequence of SEQ ID NO: 7; and
(B) a chimeric co-stimulatory receptor containing an extracellular domain containing a polypeptide derived from PD-1, a transmembrane domain, and an intracellular domain containing a polypeptide derived from 4-1BB.
It is noted that the TCR α chain CDR amino acid sequences of SEQ ID NO: 2-4 and the TCR β chain CDR amino acid sequences of SEQ ID NOs: 5-7 of the ‘664 application are 100% identical to the same sequences recited in the claims of the instant application.
Additionally, claim 2 of the instant application and claim 48 of the ‘664 application recite that the TCR is capable of binding to a PRAME peptide having the amino acid sequence SLLQHLIGL (SEQ ID NO: 1) or a portion thereof (or its HLA-A2 bound form).
Instant claim 3 and claim 49 of the ‘664 application recite that the HLA-A2 is a HLA-A*02:01, HLA-A*02:02, HLA-A*02:04 or HLA-A*02:09 encoded molecule.
Instant claim 6 and claim 50 of the ‘664 application recite the same extracellular domain and intracellular domain sequences.
Claim 7 of the instant application and claim 51 of the ‘664 application recite that the transmembrane domain is derived from PD-1.
Claim 14 of the instant application and claims 53 and 54 of the ‘664 application recite a method of treating cancer comprising administering a cell comprising a PRAME specific TCR and chimeric co-stimulatory receptor.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowable.
The art made of record and not relied upon is considered pertinent to applicant's disclosure:
Salvermoser et al. J Immunother Cancer 8(Suppl 3): A369, #614, November 2020 (teach the generation of a chimeric switch receptor comprising the extracellular domain of PD1 and the costimulatory domain of 4-1BB; disclose in the conclusion section that “equipping therapeutic T cells with the chimeric PD1-41BB switch receptor enhances T cell functionality under immunosuppressive conditions and counteracts checkpoint-mediated dysfunction”)
References that discuss the role of PRAME in cancer
Al-Khadairi et al. Cancers 11: 984, 2019
Li et al. Biomed Res Int 2020: 8828579, 2020
Xu et al. Cell Prolifer 53: e12770, 2020
Post-filing date references that teach cells comprising a PRAME-specific TCR and a PD1-41BB co-stimulatory receptor
Burdek et al. Ann Oncol 32(S5): S851-852, #1007P, 2021
Sailer et al. Cancers 14: 1998, 2022
Fetzer et al. Cancer Res 81(13 Suppl): 1521, 2021
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIDGET E BUNNER whose telephone number is (571)272-0881. The examiner can normally be reached Monday-Friday 9:00 am-6:00 pm.
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, Joanne Hama can be reached at (571) 272-2911. 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.
BEB
Art Unit 1647
22 June 2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
Prosecution Insights