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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05 January 2026 has been entered.
Status of the Claims
Applicant’s submission filed 16 December 2025 has been entered. Claims 1, 4, 6-9, 24, 27, 54, 57-58, 63-67, 69, 86, 88, 123, and 126 are pending. Claims 1, 4, 6-9, 27, 58, 63-67, 69, and 88 have been amended. Therefore, prosecution on the merits continues for claims 1, 4, 6-9, and 24 as being drawn to the elected invention, with claims 27, 54, 57-58, 63-67, 69, 86, 88, 123, and 126 withdrawn for reading on the non-elected invention(s). All arguments have been fully considered with the status of each prior ground of rejection set forth below.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 1, 4, 6-9, and 24 under 35 USC 112(a)
Applicant’s amendments to each of instant claims 1, 4, and 6-9 replacing the term “exogenetic” with “foreign” obviate the rejection of record. It is of note that the term “foreign” has written description support within Pages 18-19 of the instant Specification filed 09 September 2025, and is thereby not considered an addition of new matter.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 1, 4, 6, and 24 under 35 USC 102(a)(1) and 35 USC 102(a)(2) over Ilan et al as evidenced by Balato et al
Applicant has amended independent claim 1 to require, at least, the T cell receptor and/or the coding element therefor to be foreign-introduced. As this is a newly presented limitation that has previously not been considered, Applicant’s amendments obviate the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 1, 4, 6-7, and 24 under 35 USC 103 over Ilan et al as evidenced by Balato et al in view of Freidman et al
Applicant has amended independent claim 1 to require, at least, the T cell receptor and/or the coding element therefor to be foreign-introduced. As this is a newly presented limitation that has previously not been considered, Applicant’s amendments obviate the rejection of record.
Therefore, the rejection is withdrawn.
However, Applicant’s remarks are addressed in so far as they are applicable to the claims as currently written:
Applicant has traversed the rejection, asserting in Page 8 of the Remarks filed 16 December 2025 that Friedman et al disclose the OB gene and leptin protein it encodes, resolving the key issues of the unclear molecular mechanism of obesity, as well as the lack of targeted diagnostic and therapeutic tools. In response, the Examiner respectfully submits that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, Friedman et al was a tertiary reference relied upon to teach that the leptin protein sequence of instant SEQ ID NO: 13 was known in the art at the time of filing.
Applicant has further traversed the rejection, asserting in Page 9 of the Remarks filed 16 December 2025 that the cited art has no salient teachings that would have provided a reasonable expectation of the synergistic effect found with the co-expression of CAR/TCR + leptin/leptin receptor in immune cells. Applicant supports these assertions with Figures 1-11, 13, and 18 of the instant disclosure. In response, the Examiner respectfully reminds Applicant that, in submitting evidence asserted to establish unobvious results, there is a burden on Applicant to indicate how the examples asserted to represent the claimed invention are considered to relate to the examples intended to represent the prior art and, particularly, to indicate how those latter examples do represent the closest prior art. The evidence relied upon should also be reasonably commensurate in scope with the subject matter claimed and illustrate the claimed subject matter relative to the prior art subject matter. See MPEP § 2145. It should also be established that the differences in the results are in fact unexpected and unobvious and of both statistical and practical significance. See MPEP § 716.02(b). In the instant case, Applicant has failed to indicate how the alleged unexpected results differ from the closest prior art. It is also of note that the cited figures and corresponding results are not commensurate in scope with the instantly claimed modified immune cell, as they are directed to the co-expression of CAR-T cells with leptin/leptin receptor, while the instant claims are broadly directed to any immune cell that is modified to comprise a chimeric antigen receptor or an exogenous TCR. Furthermore, the Examiner has reviewed the data asserted by Applicant at Figures 1-11, 13, and 18 and is not convinced of a synergistic effect. More specifically, Applicant’s data does not persuasively show that the co-expression of CARs and leptin/leptin receptors within T cells led to a synergistic effect, as it fails to show the individual effect of the leptin/leptin receptors on the T cells without a CAR, which is crucial in determining if the co-expression is indeed a synergistic effect or just merely an additive effect. Therefore, the Examiner is currently interpreting Applicant’s data to show an additive effect of the leptin/leptin receptors on the CAR-T cells.
RE: Rejection of claims 1, 4, 6, 8-9, and 24 under 35 USC 103 over Ilan et al as evidenced by Balato et al in view of Jockers et al
Applicant has amended independent claim 1 to require, at least, the T cell receptor and/or the
coding element therefor to be foreign-introduced. As this is a newly presented limitation that has previously not been considered, Applicant’s amendments obviate the rejection of record.
Therefore, the rejection is withdrawn.
However, Applicant’s remarks are addressed in so far as they are applicable to the claims as currently written:
Applicant has traversed the rejection, asserting in Page 8 of the Remarks filed 16 December 2025 that Jockers et al disclose a method for detecting the binding activity and dimerization state of leptin receptor ligands, wherein the aim was to detect leptin receptor agonists/antagonists for the treatment of metabolic diseases. In response, the Examiner respectfully submits that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, Jockers et al was a secondary reference relied upon to teach that the human leptin receptor sequence of instant SEQ ID NO: 15 was known in the art at the time of filing.
Applicant has further traversed the rejection, citing the same assertions within Page 9 of the Remarks filed 16 December 2025 in regards to the unexpected results. In response, the Examiner respectfully directs Applicant to the discussion of the 35 USC 103 rejection over Ilian et al as evidenced by Balato in view of Friedman, where the assertions were addressed.
New Grounds of Rejection
Claim Objections
Claim 1 is objected to because of the following informalities:
Regarding claim 1: The instant claim is objected to for reciting “a T cell receptor” in Lines 2, 9-10, and 14-15, while reciting a “T-cell receptor” in Line 12. Applicant must amend the instant claim
such that a consistent recitation of “T cell receptor” is utilized throughout the claim language.
Appropriate correction is required.
Claim Interpretation
Under the broadest reasonable interpretation of each claim, all “optional” limitations are not required.
Claims 1, 4, 6-9, and 24 either directly require or fully incorporate the limitations requiring leptin peptides “or a functional fragment thereof”, and/or a leptin receptor “or a functional fragment thereof.” Page 14 of the instant Specification as filed 25 March 2022 teaches:
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In addition, instant claims 1, 4, 6-9, and 24 utilize or fully incorporate the term “foreign” within the claim language. The Examiner is interpreting this term to be synonymous with “exogenous”.
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.
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 1, 4, 6, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Ilan et al (US 2011/0256123 A1, of record) in view of Saint-Remy (US 2021/0015897 A1).
Ilan et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2). Saint-Remy is considered prior art under 35 USC 102(a)(2), with an effective filing date of 14 April 2017.
Regarding claim 1: Ilan et al disclose methods and uses of leptin for immune-modulation of the balance between the Th1/Th2 responses and for the treatment of immune-related disorders (Abstract).
As such, Ilan et al disclose the ex vivo education of natural killer T (NKT) cells by culturing the NKT cells in the presence of (i) an antigen or antigens associated with said immune-related disorder; (ii) an antigen presenting cell, preferably DC and (iii) an expression vector comprising a nucleic acid sequence encoding for leptin or any functional fragments thereof (Paragraphs [0056], [0058], [0104]-[0111], [0179]). Ilan et al further disclose that the antigens associated with the immune-related disorder include synthetic fragments of the antigens presented within a complex, or conjugated with a receptor or any other binding partner that aids in uptake (Paragraphs [0184]-[0185]).
Ilan et al further disclose the transfection of expression vectors into recipient cells – including NKT cells – is well-known in the art (Paragraphs [0107]-[0111]).
Ilan et al further disclose that the immune-related disorders to be treated include malignant proliferative disorders and infections caused by a pathogenic agent (Paragraphs [0026]-[0036], [0114]-[0116], [0119]-[0128], [0138]-[0141]).
Ilan et al do not disclose that the NKT cells further comprise a chimeric antigen receptor (CAR) or exogenous T cell receptor (TCR), as required by instant claim 1.
Saint-Remy, however, discloses NKT cells comprising an antigen receptor, wherein the antigen receptor is an exogenous TCR or CAR specific for an antigen-CD1 complex (Abstract; Paragraphs [0024], [0080], [0199]-[0200], [0218], [0234], [0265]-[0267]). Saint-Remy further discloses that the NKT TCR/CAR cells are used for the treatment of tumors and infections with intracellular pathogens, wherein the CD1 molecule is bound to the tumor or pathogenic antigen (Paragraphs [0014], [0024], [0234]-[0235]).
Therefore, it would have been prima facie obvious to have modified the NKT cells of Ilan et al such that they are ex vivo modified to comprise an exogenous TCR or CAR, as detailed in Saint-Remy. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to provide NKT cells carrying an exogenous antigen receptor, as it provides the antigen presentation required by Ilan et al (Paragraphs [0184]-[0185]) while also allowing for the treatment of broader group of patients suffering from cancer or pathogenic infections who are not necessarily MHC compatible (Saint-Remy: Paragraph [0218]). Furthermore, the ordinary artisan would have had a reasonable expectation of success given that the production of TCR/CAR NKT cells is well-known in the art (Saint-Remy: Paragraphs [0199]-[0200]). See MPEP § 2143(I)(G).
Consequently, Ilan et al as modified by Saint-Remy render obvious an ex vivo modified NKT cell comprising (i) a CAR or exogenous TCR specific for an antigen-CD1 complex, and (ii) an expression vector comprising a nucleic acid sequence encoding for a leptin. As the antigens within the antigen-CD1 complex do not include leptin, this therefore renders obvious the modified immune cell of the instant claim.
Regarding claim 4: Following the discussion of claim 1, Ilan et al further disclose that the exogenous leptin is derived from a human (Paragraphs [0236]-[0237]). This therefore reads on the modified immune cell of the instant claim.
Regarding claim 6: Following the discussion of claim 1, Ilan et al further disclose that the NKT cells are educated with an expression vector comprising a nucleic acid encoding secreted leptin protein (Paragraph [0004]). This therefore reads on the modified immune cell of the instant claim.
Regarding claim 24: Following the discussion of claim 1, Ilan et al further disclose that the leptin-educated NKT cells are comprised within a pharmaceutical composition comprising a pharmaceutically acceptable carrier (Paragraphs [0057], [0188]-[0189], [0208]). This therefore reads on the pharmaceutical composition of the instant claim.
Claims 1, 4, 6-7, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Ilan et al (US 2011/0256123 A1, of record) in view of Saint-Remy (US 2021/0015897 A1), and further in view of Friedman et al (US 6,124,448 A, of record).
The discussion of Ilan et al as modified by Saint-Remy regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Ilan et al as modified by Saint-Remy render obvious claims 1, 4, 6, and 24. Friedman et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claim 7: As aforementioned in the discussion of claim 1 above, Ilan et al as modified by Saint-Remy render obvious an ex vivo modified NKT cell comprising (i) a CAR or exogenous TCR specific for an antigen-CD1 complex, and (ii) an expression vector comprising a nucleic acid sequence encoding for a human leptin protein.
The combination of Ilan et al and Saint-Remy fail to teach the sequence of the encoded human leptin protein, as required by instant claim 7.
Friedman et al, however, disclose a human leptin protein having a sequence as set forth in SEQ ID NO: 4 (Columns 3, 61-62; Figure 3), which has 100% sequence identity to instant SEQ ID NO: 13 (see sequence alignment below).
Therefore, it would have been prima facie obvious to have substituted the encoded human leptin protein of Ilan et al for the human leptin protein of Friedman et al, as doing so would be a simple substitution of one human leptin sequence for another. See MPEP § 2143(I)(B). One of ordinary skill in the art would have recognized that these two human leptin sequences are functionally comparable, and thereby would have been able to substitute the sequences with predictable results.
Consequently, Ilan et al as modified by Saint-Remy and Friedman et al render obvious an NKT cell that has been modified to comprise an expression vector comprising an encoded human leptin protein having a sequence that is 100% identical to instant SEQ ID NO: 13. This therefore renders obvious the modified immune cell of the instant claim.
Query Match 100.0%; Matches 167; Mismatches 0; Gaps 0;
Qy 1 MHWGTLCGFLWLWPYLFYVQAVPIQKVQDDTKTLIKTIVTRINDISHTQSVSSKQKVTGL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MHWGTLCGFLWLWPYLFYVQAVPIQKVQDDTKTLIKTIVTRINDISHTQSVSSKQKVTGL 60
Qy 61 DFIPGLHPILTLSKMDQTLAVYQQILTSMPSRNVIQISNDLENLRDLLHVLAFSKSCHLP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DFIPGLHPILTLSKMDQTLAVYQQILTSMPSRNVIQISNDLENLRDLLHVLAFSKSCHLP 120
Qy 121 WASGLETLDSLGGVLEASGYSTEVVALSRLQGSLQDMLWQLDLSPGC 167 (Instant SEQ ID NO: 13)
|||||||||||||||||||||||||||||||||||||||||||||||
Db 121 WASGLETLDSLGGVLEASGYSTEVVALSRLQGSLQDMLWQLDLSPGC 167 (SEQ ID NO: 4)
Claims 1, 4, 6, 8-9, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Ilan et al (US 2011/0256123 A1, of record) in view of Saint-Remy (US 2021/0015897 A1), and further in view of Jockers et al (US 2004/0132093 A1, of record).
The discussion of Ilan et al as modified by Saint-Remy regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Ilan et al as modified by Saint-Remy render obvious claims 1, 4, 6, and 24. Jockers et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claims 8-9: Following the discussion of claim 1 above, Ilan et al further disclose that the NKT cell can be educated with fragments of leptin receptors, including leptin receptor isoforms (Paragraphs [0044], [0056], [0082]-[0083]). It is of note that since this is an exogenous receptor being introduced into the NKT cell, the NKT cell will inherently express an increased amount of the leptin receptor when compared to an unmodified NKT cell. See MPEP § 2112.
The combination of Ilan et al and Saint-Remy fail to teach that the leptin receptor isoform comprises at least a transmembrane domain, nor the corresponding sequences of the transmembrane domain, as required by instant claims 8-9.
Jockers et al, however, disclose a method for detecting leptin receptor ligands (Abstract). As such, Jockers et al disclose leptin receptor isoforms, wherein the leptin receptor comprises a transmembrane domain (Paragraphs [0004]-[0005], [0031], [0033]; Figure 1). Jockers et al further disclose that the leptin receptor isoform is the isoform having a sequence according to SEQ ID NO: 2 (Paragraph [0033]), which has 100% identity to instant SEQ ID NO: 15 (see sequence alignment below).
Therefore, it would have been prima facie obvious to have substituted the leptin receptor isoform within the expression vector of Ilan et al with the leptin receptor isoform comprising a transmembrane domain sequence as detailed in Jockers et al, as doing so would have been a simple substitution of one known leptin receptor isoform sequence for another. See MPEP § 2143(I)(B). One of ordinary skill in the art would have recognized that these two leptin receptors and corresponding sequences are functionally comparable, and thereby would have been able to substitute the leptin receptor isoforms with predictable results.
Consequently, Ilan et al as modified by Saint-Remy and Jockers et al render obvious an NKT cell that has been educated with an expression vector comprising an encoded leptin receptor isoform as detailed in SEQ ID NO: 2 of Jockers et al. As SEQ ID NO: 2 of Jockers et al has 100% sequence identity to instant SEQ ID NO: 15 – which corresponds to the transmembrane domain of the leptin receptor (claim 8) – this therefore renders obvious the modified immune cell of instant claim 9.
Query Match 100.0%; Matches 28; Mismatches 0; Gaps 0;
Qy 1 DAGLYVIVPVIISSSILLLGTLLISHQR 28 (Instant SEQ ID NO: 15)
||||||||||||||||||||||||||||
Db 839 DAGLYVIVPVIISSSILLLGTLLISHQR 866 (SEQ ID NO: 2)
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633