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 the Claims
Applicant’s submission filed 26 May 2026 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, 24, 27, 54, 58, 63-67, 69, 86, 88, and 123 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1, 4, 6-9, and 24 as being drawn to the elected invention, with claims 27, 54, 57-58, 63-67, 69, 86, 88, 123, and 126 withdrawn for reading on the non-elected invention(s).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: Objection to claim 1
Applicant asserts in Page 7 of the Remarks filed 26 May 2026 that instant claim 1 has been amended to use the consistent recitation of “T cell receptor”. However, Applicant has failed to alter the recitation of “T-cell receptor” in Line 12.
Therefore, the objection is maintained.
RE: Rejection of claims 1, 4, 6, and 24 under 35 USC 103 over Ilan et al in view of Saint-Remy
Applicant's arguments filed 26 May 2026 have been fully considered but they are not persuasive.
Applicant has traversed the rejection, asserting in Pages 7-8 of the Remarks filed 26 May 2026 that Ilan et al fail to disclose a T cell that itself comprises a foreign leptin and/or foreign leptin receptor, rather teaching the co-culture of NKT cells with an exogenous leptin as an external stimulus. In response, the Examiner respectfully submits that Ilan et al disclose that NKT cells are educated with an expression construct comprising a nucleic acid encoding leptin. Ilan et al further disclose that the term “construct” is defined as a vector such as a plasmid, virus, bacteriophage, integratable DNA fragment, and other vehicle which enables the integration of DNA fragments into the genome of the host cell. See, for example, Paragraphs [0105] and [0179] of Ilan et al. Ilan et al further disclose in Paragraphs [0107]-[0111] of the disclosure that the transfection of constructs into recipient cells – including NKT cells – is well-known in the art. Therefore, the ordinary artisan would have recognized that the educated NKT cells are transfected with the expression construct and thereby comprise the encoded leptin with their genome.
Applicant has further traversed the rejection, asserting in Pages 8-9 of the Remarks filed 26 May 2026 that Ilan et al and Saint-Remy have different antigen recognition systems, wherein the NKT cells of Ilan et al function through an antigen presentation system centered on dendritic cell co-culture. Applicant furthers this assertion by stating that the ordinary artisan would not have been motivated to include the group 1 CD1-restricted CAR/TCR of Saint-Remy within the NKT cells of Ilan et al, as Ilan et al only describe antigens presented through a CD1d-glycolipid pathway. In response, the Examiner respectfully submits that Ilan et al disclose that several cell types appear to be capable of serving as antigen presenting cells – including dendritic cells (DC), activated B cells, and activated macrophages – and is not limited to the exemplary cell types which are specifically mentioned and exemplified within the disclosure. See, for example, Paragraph [0181] of Ilan et al. Accordingly, the disclosure of Ilan et al is not limited to an antigen presentation system centered on dendritic cell co-culture, nor does Ilan et al explicitly specify that the antigens are presented through a CD1d-glycolipid pathway anywhere within the disclosure. It is also of note that Saint-Remy discloses the co-culture of NKT cells with dendritic cells serving as antigen presenting cells. See, for example, Paragraph [0166] of Saint-Remy. Therefore, the ordinary artisan would have reasonably expected the antigen recognition systems between Ilan et al and Saint-Remy to be compatible.
Applicant has further traversed the rejection, asserting in Pages 9-10 of the Remarks filed 26 May 2026 that the ordinary artisan would not have arrived at the triple-element construct of the instant claims given the disclosures of Ilan et al and Saint-Remy with a reasonable expectation of success. In response, the Examiner respectfully submits that the features upon which Applicant relies (i.e., a triple-element construct comprising a (i) CAR or exogenous TCR, (ii) leptin, and (iii) leptin receptor) are not necessarily required within the recited claims. More specifically, the instant claims require the modified immune T cell to comprise (i) a CAR or exogenous TCR, and (ii) a leptin or leptin receptor. Furthermore, the Examiner respectfully submits that it is not required that the expectation of success be a certainty; only one that is reasonable to a person of ordinary skill. In re Longi, 759 F.2d 887, 897 (Fed. Cir. 1985) (“Only a reasonable expectation of success, not absolute predictability, is necessary for a conclusion of obviousness”). In the instant case, the ordinary artisan would have had a reasonable expectation of success given that Ilan et al disclose an antigen-educated leptin-comprising NKT cell, and the production of TCR/CAR NKT cells is well-known in the art.
Applicant has lastly traversed the rejection, asserting in Pages 10-11 and 14-15 of the Remarks filed 26 May 2026 that the experimental data yielded unexpected results. More specifically, Applicant asserts that the co-expression of leptin and/or leptin receptor in CAR-T cells produces substantial increases in the proportions of Tscm and Tcm, and allows for complete tumor elimination at low doses with extremely low recurrence rates compared to CAR-only controls. Applicant supports these assertions with Figures 1-11 and 13-18 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 – which is the antigen-educated leptin-comprising NKT cell of Ilan et al. It is also of note that the cited figures and corresponding results are not commensurate in scope with the instantly claimed modified T 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 a T cell that is modified to comprise a chimeric antigen receptor or an exogenous TCR.
Therefore, the rejection is maintained.
RE: Rejection of claims 1, 4, 6-7, and 24 under 35 USC 103 over Ilan et al in view of Saint-Remy, and further in view of Freidman et al
Applicant's arguments filed 26 May 2026 have been fully considered but they are not persuasive.
Applicant has traversed the rejection, citing the same assertions within Pages 7-11 of the Remarks filed 26 May 2026. In response, the Examiner respectfully directs Applicant to the discussion of the 35 USC 103 rejection over Ilan et al in view of Saint-Remy, wherein the assertions were addressed.
Applicant has further traversed the rejection, asserting in Pages 11-12 of the Remarks filed 26 May 2026 that Friedman et al disclose leptin sequences within the context of metabolic disease research and has no connection to T cell engineering. 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.
Therefore, the rejection is maintained.
RE: Rejection of claims 1, 4, 6, 8-9, and 24 under 35 USC 103 over Ilan et al in view of Saint-Remy, and further in view of Jockers et al
Applicant's arguments filed 26 May 2026 have been fully considered but they are not persuasive.
Applicant has traversed the rejection, citing the same assertions within Pages 7-11 of the Remarks filed 26 May 2026. In response, the Examiner respectfully directs Applicant to the discussion of the 35 USC 103 rejection over Ilan et al in view of Saint-Remy, wherein the assertions were addressed.
Applicant has traversed the rejection, asserting in Page 13 of the Remarks filed 26 May 2026 that Jockers et al disclose leptin sequences within the context of metabolic drug screening assays and has no connection to immune cell engineering, T cell biology, or CAR constructs. 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 tertiary 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.
Therefore, the rejection is maintained.
Maintained 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 remain 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, of record).
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]). It is of note that an “expression vector” is defined by Ilan et al as a vector which enables the integration of DNA fragments into the genome of the host cell (Paragraph [0105]).
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 T 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 T 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 T 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 remain 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, of record), 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 T 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 remain 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, of record), 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 T 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
THIS ACTION IS MADE FINAL. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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
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