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 .
The Examiner of your application in the USPTO has changed. To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Kimberly Ballard, Art Unit 1675.
Election/Restrictions
1. Applicant's election with traverse of species within each of A-K in the reply filed on July 31, 2025 is acknowledged. The traversal is on the ground(s) that the examiner has not shown a serious burden would be required to examine all species in any of the A-K groups. Applicant indicates that the claims encompassing the elected species include claims 1-12, 15-18 and 28-30.
Applicant’s arguments have been considered and are persuasive. Accordingly, the species election requirement in the restriction mailed 06/03/2025 is hereby withdrawn.
2. Claims 1-12, 15-18 and 28-30 are under examination in the current office action.
Information Disclosure Statement
3. The information disclosure statements (IDSs) filed 06/08/2022, 04/02/2025 and 11/05/2025 have been considered and the references therein are of record.
Nucleotide and/or Amino Acid Sequence Disclosures
4. 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.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
In particular, Figures 1, 2 and 3 all contain amino acid sequences that required sequence identifiers.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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.
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). See, for example, in claim 11 and at least at paragraphs [0002], [0018], [0027], [0164], and [0223]. Applicant is reminded to review the entire specification for additional instances of sequences requiring sequence identifiers.
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.
Drawings
5. The drawings are objected to because the label in Figure 1 does not match the brief description of the figure at paragraph 0002 of the specification. In particular, Figure 1 shows a picture of an orthogonal IL2Rb extracellular domain (ECD) plus a wild-type IL2Rb transmembrane and intracellular domain (TM/ICD) plus a STAT3 motif. However, the STAT3 motif is labeled as a “STAT4 motif” (right bottom of figure). 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.
Specification
6. The disclosure is objected to because of the following informalities:
Paragraph [0050] of the specification states “the STAT5 motif YYLSL (SEQ ID NO: 20)”, which is not the same amino acid sequence that appears in the sequence listing for SEQ ID NO: 20. The sequence listing lists SEQ ID NO: 20 as YLSL, which is also stated, for example at paragraph [0051]. Therefore, the sequence “YYLSL” is either a typographical mistake or it represents a new sequence that is not listed in the CRF sequence listing. Appropriate correction is required.
Claim Objections
7. Claims 8 and 18 are objected to because of the following informalities:
Claim 8 requires an “and” between “F” and “M” for the X1 grouping.
Claim 18 recites an acronym that is not spelled out in its first use in the claims (i.e., BCMA). It would be remedial to amend the claim language in claim 18 such that the acronym is clearly defined. Appropriate correction is required.
Claim Rejections - 35 USC § 102
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.
8. Claim(s) 1-6, 15-16 and 28-30 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Garcia et al. (US 2018/0228842 A1; listed on 06/08/2022 IDS) as evidenced Delespine-Carmagnat et al. (Eur J. Immunol. 2000, 30:59-68).
Garcia et al. teach a polynucleotide molecule encoding an orthogonal human CD122 protein (also referred to as IL-2 receptor beta or IL2Rb)(see claims 8 and 18 at p. 29; and [0098]), an expression vector comprising the nucleic acid molecule (see claim 19 and [0009]), and a cell genetically engineered to comprise the vector (see claim 20 and [0008]). Garcia teaches that the human CD122 (hCD122) protein is engineered to express amino acid substitutions at one or more of the following positions: R41, R42, Q70, K71, T73, T74, V75, S321, H133, Y134, F135, E136 and Q214 ([0098]), which is directly on point to the limitations of present claim 3.
In particular, Garcia teaches a modified hCD122 that is modified at H133D and Y134F (Garcia’s SEQ ID NO: 9), and which is 99.5% identical to the sequence of instant SEQ ID NO: 1. See the alignment below, in which in Qy is the instant SEQ ID NO: 1, and Db is Garcia’s SEQ ID NO: 9 (substituted residues bolded and boxed).
Query Match 99.5%; Score 2833; Length 525; Best Local Similarity 99.6%; Matches 522; Conservative 1; Mismatches 1; Indels 0; Gaps 0;
Qy 1 AVNGTSQFTCFYNSRANISCVWSQDGALQDTSCQVHAWPDRRRWNQTCELLPVSQASWAC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AVNGTSQFTCFYNSRANISCVWSQDGALQDTSCQVHAWPDRRRWNQTCELLPVSQASWAC 60
Qy 61 NLILGAPDSQKLTTVDIVTLRVLCREGVRWRVMAIQDFKPFENLRLMAPISLQVVHVETH 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NLILGAPDSQKLTTVDIVTLRVLCREGVRWRVMAIQDFKPFENLRLMAPISLQVVHVETH 120
[AltContent: rect]
Qy 121 RCNISWEISQASHYFERHLEFEARTLSPGHTWEEAPLLTLKQKQEWICLETLTPDTQYEF 180
|||||||||||| :||||||||||||||||||||||||||||||||||||||||||||||
Db 121 RCNISWEISQASDFFERHLEFEARTLSPGHTWEEAPLLTLKQKQEWICLETLTPDTQYEF 180
Qy 181 QVRVKPLQGEFTTWSPWSQPLAFRTKPAALGKDTIPWLGHLLVGLSGAFGFIILVYLLIN 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QVRVKPLQGEFTTWSPWSQPLAFRTKPAALGKDTIPWLGHLLVGLSGAFGFIILVYLLIN 240
Qy 241 CRNTGPWLKKVLKCNTPDPSKFFSQLSSEHGGDVQKWLSSPFPSSSFSPGGLAPEISPLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CRNTGPWLKKVLKCNTPDPSKFFSQLSSEHGGDVQKWLSSPFPSSSFSPGGLAPEISPLE 300
Qy 301 VLERDKVTQLLLQQDKVPEPASLSSNHSLTSCFTNQGYFFFHLPDALEIEACQVYFTYDP 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 VLERDKVTQLLLQQDKVPEPASLSSNHSLTSCFTNQGYFFFHLPDALEIEACQVYFTYDP 360
Qy 361 YSEEDPDEGVAGAPTGSSPQPLQPLSGEDDAYCTFPSRDDLLLFSPSLLGGPSPPSTAPG 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 YSEEDPDEGVAGAPTGSSPQPLQPLSGEDDAYCTFPSRDDLLLFSPSLLGGPSPPSTAPG 420
Qy 421 GSGAGEERMPPSLQERVPRDWDPQPLGPPTPGVPDLVDFQPPPELVLREAGEEVPDAGPR 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 GSGAGEERMPPSLQERVPRDWDPQPLGPPTPGVPDLVDFQPPPELVLREAGEEVPDAGPR 480
Qy 481 EGVSFPWSRPPGQGEFRALNARLPLNTDAYLSLQELQGQDPTHL 524
||||||||||||||||||||||||||||||||||||||||||||
Db 481 EGVSFPWSRPPGQGEFRALNARLPLNTDAYLSLQELQGQDPTHL 524
As evidenced by Delespine-Carmagnat et al., the acidic subdomain region of IL-2Rb (i.e., residues 306-383 of SEQ ID NO: 1; see Fig. 1 at p. 61) has been shown to associate with STAT3 (see Fig. 5 at p. 63, which shows association of STAT3 with the acidic subdomain of IL-2Rb (GST-bAci or GST-bAci*)). This region includes four tyrosine (Y) residues (Y338, Y355, Y358 and Y361 – shown as underlined bold in the alignment above), and comprises the STAT3 recognition motifs YFTY, YDPY and YSEE that are found between residues 355 to 364 (as in present claim 11). Thus, the hCD122 protein (i.e., hIL-2Rb) inherently comprises one or more STAT3 binding motifs as recited in present claim 1.
Accordingly, Garcia teaches a polynucleotide encoding a modified human CD122 (Garcia’s H133D/Y134F hCD122 or SEQ ID NO: 9) that comprises one or more STAT3 binding motifs, and thus anticipates claim 1.
Regarding claims 2 and 5, Garcia teaches that the modified hCD122 is an orthogonal hCD122. Also, because there is no limiting definition for “fused” (i.e., fused to one or more STAT3 binding motifs) in claim 2, the broadest reasonable interpretation (BRI) of this limitation would include polynucleotide sequences in which the STAT3 binding motif is operably linked with the CD122 sequence, which would include sequences that comprise the STAT3 binding motifs. Garcia teaches an orthogonal hCD122 that comprises one or more STAT3 binding motifs, and therefore meets the limitations of the BRI of claim 2. Similarly, the orthogonal hCD122 polypeptide of Garcia inherently comprises three STAT3 binding motifs (as evidenced by present claim 11), which thus addresses claim 5 (the human CD122 is linked to two or three STAT3 binding motifs).
Regarding claims 3-4, Garcia teaches all of the modification sites in claim 3 (see above) and teaches the H133D/Y134F orthogonal hCD122 of SEQ ID NO: 9.
Regarding claim 6, Garcia’s polypeptide sequence of SEQ ID NO: 9 is 99.5% identical to the sequence of instant SEQ ID NO: 1, which is at least 90% identical. Also, Garcia teaches that the orthogonal CD122 binds to an orthogonal IL2 (see [0097] and [0100]).
The limitations of claims 15 and 16 have been addressed as discussed above in that Garcia both teaches and claims expression vectors and cells comprising the polynucleotide that encodes for the orthogonal hCD122 (see also [0107]).
And regarding claims 28-30, Garcia teaches that immune cells, such as T cells (see [0106]), may be engineered by introduction of an orthologous receptor of the invention (e.g., an orthologous hCD122 of SEQ ID NO: 9) (see [0105]). Garcia indicates that the cell population may be engineered ex vivo (see [0108]), where the cells are contacted with the orthologous cytokine (e.g., hIL-2) in vitro (see [0109]). Conversely, Garcia teaches that where the contacting of engineered cells with cytokine is performed in vivo, an effective dose of engineered cells is infused to the recipient, in combination with or prior to administration of the orthologous cytokine (see [0110]).
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.
9. Claim(s) 17-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Garcia et al. (US 2018/0228842 A1; listed on 06/08/2022 IDS) in view of Sockolosky et al. (Science, 2018, 359(6379):1037-1042) and Ma et al. (WO 2016/210293 A1).
The teachings of Garcia et al. are discussed above and provide for a cell comprising a polynucleotide encoding an orthogonal hCD122 comprising the substitutions of H133D/Y134F (SEQ ID NO: 9) that inherently comprises one or more STAT3 binding motifs (as evidenced by Delespine-Carmagnat et al. cited above). Garcia teaches that the cell is an immune cell or T cell (see [0106], [0053]), such as a human cell ([0113]), which is on point to one limitation of present claim 17 (the cell is a human immune cell). However, Garcia does not teach that the cell further comprises a chimeric antigen receptor (CAR) (claim 17), or that CAR is selected from a CD19 CAR or a BCMA CAR (claim 18).
Consistent with the teachings of Garcia, Sockolosky et al. teach engineered T cell that are modified to expresses orthogonal IL-2Rb (CD122) to be used in conjunction with orthogonal IL-2. Notably, the Sockolosky publication is from the same inventive group as the Garcia document, and thus the teachings are cumulative with those of Garcia. Sokolosky teaches that their results “constitute an approach to redirect the specificity of IL-2 toward engineered T cells using orthogonal IL-2 cytokine-receptor pairs, which enables the selective expansion of desired T cell subsets in settings of adoptive cell therapy, but with limited off-target activity and negligible toxicity” (p. 5 of 6, sentence spanning middle and right columns). Sockolosky further suggests that “[o]rthogonal IL-2/IL-2R pairs may be useful not only as a research tool but in the clinic to specifically enrich transduced T cells that express a target gene of interest, such as a CAR or engineered TCR, when coupled with expression of the orthoIL-2Rb” (p. 5 of 6, right column). The recitation of “clinical” utilization also implicitly provides for the use of human immune cells.
Ma et al. teach engineered cells comprising at least one chimeric antigen receptor (CAR) polypeptide (Abstract; p. 3 line 15-22), wherein the cells can include T cells or NK cells (i.e., immune cells) (p. 33 lines 8-19). The targeted antigen of the CARs can be CD19 or BCMA, among other cell surface antigens (p. 4 lines 17-19; p. 25 lines 9 and 14), which addresses limitations of present claims 17 and 18. Ma further teaches that the engineered cells may also express an enhancer (i.e., a biological molecule that promotes or enhances the activity of the engineered cell having the CAR polypeptide), including IL-2 and its receptor (p. 41 line 20–p. 42 line 4).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a CAR human T cell, instead of a non-CAR T cell as taught by Garcia, to express an orthogonal hIL-2Rb (hCD122) and thereby arrive at the presently claimed invention. The artisan would have been motivated by the Sockolosky reference, which suggests that engineered CAR T cells made to express orthoIL-2Rb would be clinically useful. And given the teachings of Ma indicating that CAR T cells can also express enhancer molecules, such as IL-2R, and the teachings of both Garcia and Sokolosky demonstrating successfully modified T cells that express orthoIL-2Rb, the artisan would have had a reasonable expectation that a CD19-CAR or BCMA-CAR T cell expressing orthoIL-2Rb could not only be made, but also successfully used. The combined teachings of the prior art references thus render obvious the invention of present claims 17-18.
10. Claim(s) 7-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Garcia et al. (US 2018/0228842 A1; listed on 06/08/2022 IDS) in view of Fung et al. (Cell Signal. 2003, 15:625-636), and Tanaka et al. (WO 2016/127257 A1; listed on IDS).
The teachings of Garcia et al. are discussed above and provide for a polynucleotide encoding an orthogonal hCD122 comprising the substitutions of H133D/Y134F (SEQ ID NO: 9) that inherently comprises one or more STAT3 binding motifs (as evidenced by Delespine-Carmagnat et al. cited above), which also addresses limitations of present claim 12 (the modified human CD122 is further modified at one or more residues selected from R41, R42, Q70, K71, T73, T74, V75, S321, H133, Y134, F135, E136 and Q214 ([0098])).
However, Garcia does not teach that the one or more STAT3 binding motifs comprise a sequence of YX1X2Q (claim 7); wherein X1 is selected from L, R, F or M, and X2 is selected from R, K, H and P (claim 8); the STAT3 recognition motif is selected from one of SEQ ID NOs: 11-18 (claim 9); the one or more STAT3 binding motifs are fused to a C-terminus of the intracellular domain of the native human CD122 or the orthogonal human CD122, optionally through a linker (claim 10); at least one of the STAT3 binding motifs located between position 355 and position 364 corresponding to native human CD122, and wherein the at least one of the STAT3 recognition motif replaces an amino acid sequence of YFTY, YDPY, or YSEE in native CD122 (claims 11-12).
Fung et al. teach that in activated human T cells IL-2 stimulated STAT3 activation correlates with cell cycle progression and proliferation (see abstract and p. 634). Fung teaches that the results of the study suggest that distinct signal transduction pathways mediate biological effects of IL-2, and that the PI3K, Ras/ERK and JAK/STAT3 pathways are among the signaling pathways devoted to promoting T cell proliferation. Fung further teaches that studies of the IL-2R b-chain indicate that the biological effects of IL-2 are induced by specific signaling motifs on the receptor itself, and that different signaling molecules associate with these distinct regions of IL-2Rb, thereby resulting in the differentiation of signaling pathways to mediate T cell proliferation and anti-apoptosis (p. 635, paragraph spanning columns).
Accordingly, Fung establishes that STAT3 activation and signaling in IL-2/IL-2R-mediated T cell activation is necessary for cell proliferation.
Tanaka et al. teach chimeric antigen receptors (CARs) that comprise an intracellular domain comprising an interleukin receptor chain, a JAK-binding motif, as STAT5 association motif and/or a CD3zeta intracellular signaling domain comprising an exogenous STAT3 association motif (see abstract and [0003]). Tanaka indicates that the STAT3 association motif is YXXQ, and in particular, YRHQ ([00011]-[00012]), which addresses limitations of present claims 7-9. The exogenous STAT3 association motif may be less than 100 amino acid residues from the C-terminus of the CAR ([00013]) (i.e., the one or more STAT3 binding motifs are fused to a C-terminus of the intracellular domain, claim 10) or else the STAT3 association motif may replace certain amino acids within the intracellular domain of CD3zeta ([00014])(i.e., the STAT3 recognition motif replaces an amino acid sequence of YFTY, YDPY or YSEE, claim 11). Tanaka teaches that the STAT3 association motif can also be introduced into signaling domains which do not comprise the YXXQ exogenous STAT3 association motif ([0005]).
Additional STAT3 association motifs are taught to include YLRQ, YFKQ, YLPQ, YMPQ, YKPQ, YRPQ and YLKQ, among others ([00075]), which addresses additional limitations of claim 9. Tanaka discloses that the intracellular segment comprises STAT3 and STAT5 association motifs, including multiple STAT3 and/or multiple STAT5 association motifs ([00076]), which addresses one or more STAT3 binding motifs in the present claims.
Tanaka further teaches that the STAT3 and STAT5 association motifs can be located or introduced into any of the intracellular signaling domains ([00077]). The reference also teaches that the cytoplasmic domain of IL-2 receptor b-chain (i.e., CD122) may be used, which IL-2Rb cytoplasmic domain may contain a STAT5 or STAT3 association motif ([00068]). An anti-CD19 CAR comprising a single-chain variable fragment (scFv) linked to CD28, the cytoplasmic domain of IL-2Rb, and CD3z with an exogenous YXXQ motif (28-IL2RB-z(YXXQ)) is demonstrated, for instance, in Example 1 and Fig. 1.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the orthogonal IL-2Rb (CD122) of Garcia to include an exogenous STAT3 association motif as taught by Tanaka and thereby arrive at the presently claimed invention. Given the teachings of Fung, the artisan would have recognized that STAT3 is necessary for IL-2 mediated T cell proliferation. And in the case of an engineered T cell, the skilled artisan would have also recognized that the orthogonal IL-2/IL-2Rb system as taught by Garcia could be further modified to include additional STAT3 binding motifs, and/or to replace the endogenous STAT3 association motifs with exogenous motifs, so as to better facilitate STAT3 signaling and thus increase proliferation of the engineered T cells. Accordingly, the motivation to modify the orthogonal IL-2Rb (CD122) of Garcia would have come from the teachings of Fung as well as Tanaka, who also provides a reasonable expectation that such a modified CD122 could be successfully made and used given the demonstrated modification of a CAR. The combined teachings of the prior art references therefore render obvious the presently recited invention of claims 7-12.
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.
11. Claims 1-6, 15-18 and 28-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5-8, 11-12, 33 and 37 of copending Application No. 17/916,739 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because in each case the claims are directed to a polynucleotide encoding a modified human orthogonal CD122 having the same H133D and Y134F substitutions, vector comprising same, modified human immune cells comprising the polynucleotide, and method of expanding said cells. As discussed above and evidenced by Delespine-Carmagnat et al. (cited above), CD122 inherently comprises one or more STAT3 recognition motifs, as recited in the present claims. Further, the ‘739 co-pending claims recite that the immune cell is a human lymphocyte that expresses a chimeric antigen receptor (CAR), wherein the CAR is CD19 or a B-cell Maturation antigen (BCMA). The co-pending ‘739 claims thus teach or render obvious the presently claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
12. No claims are allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly A. Ballard whose telephone number is (571)272-2150. The examiner can normally be reached Mon-Fri 8AM - 5PM EST.
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/KIMBERLY BALLARD/Primary Examiner, Art Unit 1675