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 .
Priority
This application is a CON of PCT/US2020/034233 filed 05/22/2020. PCT/US2020/034233 has PRO 62/852,055 filed 05/23/2019.
Claim Status
Claims 1, 4-10, 12, 14-15, 17-18, 20-25, 27, 31-32, 43, and 55-57 are pending. Claim 2-3, 11, 13, 16, 19, 26, 28-30, 33-42, 45-54 are canceled. Claim 1 and 20 are amended. Claims 43 is withdrawn. Claims 1, 4-10, 12, 14-15, 17-18, 20-25, 27, 31-32, and 55-57 are being examined on the merits in this office action.
Claim Objections - Withdrawn
The objection of claim 1 is withdrawn in view of the claim amendments.
Claim Rejections - 35 USC § 112 - Withdrawn
The rejection of claim 20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of the claim amendments.
Claim Rejections - 35 USC § 103 – Maintained
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.
Claims 1, 4-10, 12, 14-15, 17-18, 20-25, 27, 31-32, and 55-57 remain rejected under 35 U.S.C. 103 as being unpatentable over Santamaria (US20170274096A1 – hereinafter “Santamaria”) in view of Girardi et al. (J. Biol. Chem. 2016 Mar 22;291(20):10677–10683) and Blumberg et al. (WO2018053069A1 – hereinafter “Blumberg”).
Santamaria teaches an antigen/MHC/co-stimulatory molecule complex operatively coupled to a nanoparticle in an amount sufficient to expand a population of antigen-specific anti-tumorigenic T cells (claims 1-2; [0005-0008]), and that the T cell is a CD8+ or a CD4+ T cell or a NKT cell [0012, 0024, 0104]. Santamaria further teaches antigen/MHC/nanoparticle complexes without co-stimulatory molecules (claim 32; [0008, 0073]). Santamaria teaches that non-classical MHC molecules are also contemplated for use in MHC complexes of the invention [0021, 0097] and that CD1 molecules are an example of a non-classical MHC molecule [0024]. Santamaria teaches that the peptide are associated with the MHC molecule [0109] and that the non-classical MHC comprises binding pockets [0024]. Santamaria teaches that the antigen is a molecule that can induce an immune response [0044].
Santamaria does not specifically teach that the antigen is a sphingolipid, and does not teach the CD1d sequence of SEQ ID Nos. 1-4 as recited in claims 9-10, and 12.
Girardi teaches that sphingolipids such as α-GalCer are an example of an antigen which is known to bind to non-classical MHC CD1d (Page 10679, right col., 1st paragraph). Girardi teaches that the sphingolipids are known to illicit an immune response (Page 10677, let col., line 1-36).
Blumberg teaches pharmaceutical compositions that comprises MHC Class 1-related molecule such as CD1d (claim 9; [0012, 0016]) which has the amino acid sequence of SEQ ID NO: 30 (claims 20, 56; [0027, 0063]), which is identical to the instant SEQ ID NO: 1-4.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of Santamaria and use a sphingolipid such as α-GalCer as the antigen since Girardi teaches that they are known to bind non-classical MHC such as CD1d (Page 10679, right col., 1st paragraph). It would have been obvious to use the CD1d sequence of SEQ ID NO: 30 as taught by Blumberg as the non-classical MHC, since Blumberg similarly teaches composition comprising an antigen and MHC molecules such as CD1d (claims 5-7) which is also taught by Santamaria. One of ordinary skill in the art would have had a reasonable expectation of success in using α-GalCer as the antigen since Girardi teaches that α-GalCer in combination with CD1d has been shown to expand T cells (Abstract). One of ordinary skill in the art would also be motivated to use the CD1d sequence of Blumberg to combine with the antigen and the nanoparticle.
Regarding the limitation “..wherein the non-classical MHC-nanoparticle generates immunoregulatory iNKT cells that express high levels of IL-10, IL-21, MAF, and at least one of LAG3, CTLA4, SLAMF6, and ITAG4, or a combination thereof”, Examiner notes that the limitation recites an intended result. When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. MPEP 2112.01 (I). The disclosures render obvious claim 1.
Regarding claim 4-6, Santamaria teaches a composition comprising an antigen/MHC/co-stimulatory molecule complex operatively coupled to a nanoparticle, that the composition expands a population of antigen-specific anti-tumorigenic T cells (claims 1-2; [0005-0008]), that the antigen/MHC/nanoparticle complexes without co-stimulatory molecules (claim 32). Santamaria does not specifically teach that the antigen is a sphingolipid, however, as evidenced by Girardi, sphingolipids such as α-GalCer is an example of an antigen which is known to be bound to non-classical MHC CD1d (Page 10679, right col., 1st paragraph). α-GalCer is also known as Alpha-galactosylceramide or KRN7000 which is also a sphingolipid. It would have been obvious to use an antigen of Girardi such as α-GalCer in the nanoparticle of Santamaria.
Regarding claims 7-8, Santamaria teaches non-classical MHC molecule is CD1 protein (claim 5; [0021, 0024]). Further, Girardi teaches that sphingolipids such as α-GalCer are an example of an antigen which is known to bind to non-classical MHC CD1d (Page 10679, right col., 1st paragraph) and further teaches human CD1d (Page 10682, left col., 1st paragraph). It would have been obvious to use CD1d as the non-classical MHC.
Claim 9-10 and 12, Blumberg teaches pharmaceutical compositions that comprises MHC Class I-related molecule such as CD1d (claim 9; [0012, 0016]) which has the amino acid sequence of SEQ ID NO: 30 (claims 20, 56; [0027, 0063]), which reads on 90% sequence identity to instant SEQ ID NO: 1-4. ). It would have been obvious to use the CD1d sequence of SEQ ID NO: 30 as taught by Blumberg as the non-classical MHC, since Blumberg similarly teaches composition comprising an antigen and MHC molecules such as CD1d (claims 5-7) which is also taught by Santamaria.
Regarding claims 14, Blumberg teaches that the non-classical MHC comprises β2 microglobulin [00135-00136, 00130]. It would have been obvious to use an MHC molecule which includes comprises β2 microglobulin as taught by Blumberg.
Regarding claims 15, Blumberg teaches that the β2 microglobulin comprises the sequence of SEQ ID NO: 4 (Claim 2; [0009, 00136]) which is identical to the instant SEQ ID NO: 5. It would have been obvious to use the non-classical MHC which comprises the β2 microglobulin sequence taught by Blumberg.
Regarding claims 17-18, Santamaria teaches that the nanoparticle comprises one or more of a metal such as iron or iron oxide (claims 13-14; [0023, 0188].
Regarding claims 20-21, Santamaria teaches the nanoparticle is about 1 nm to about 100 nm in diameter. Preferably, the nanoparticle is about 5 nm to about 15 nm in diameter. In another embodiment the diameter of the nanoparticle is about 5 to about 25 nm, or about 1 nm to about 50 nm, or about 2 to about 25, or about 1 nm to about 10 nm, or about 10 nm to about 20 nm or about 1 nm to about 30 nm (claims 1-2, 30-31, 3538-39; [0023]).
Regarding claims 22-24, Santamaria teaches wherein said nanoparticle is covalently bound to the MHC group of the antigen/MHC complex and further wherein said binding is optionally via a linker (claims 16-17, 55; [0021, 0051, 0124]), wherein the linker is dextran and poly(ethylene glycol) (claims 20, 59; [0016, 0128]), using linkers of different sizes such as 2 kD and 5 kD, or 3.4kD [0165, 0189].
Regarding claim 25, Santamaria teaches wherein the polymer linker is 3.4 kda or 2 kda, or 5kda [0165, 0189].
Regarding claim 27, Santamaria teaches wherein polypeptide complexes are added to the nanoparticles to yield nanoparticles with adsorbed or coupled polypeptide complexes having a ratio of number of molecules:number of nanoparticles from about, at least about or at most about 0.1, 0.5, 1, 10, 100, 500, 1000 or more to: 1, more typically 0.1 : 1 to 50: 1 [0098, 0101].
Regarding claim 31, Santamaria teaches composition comprising tumor-specific antigenic molecules [0017] comprising a plurality antigen/MHC/co-stimulatory molecule/nanoparticle complexes (claim 64-65; [0074-0077, 0081], that the compositions are dispersed in a pharmaceutically acceptable carrier or aqueous medium [0085-0087].
Regarding claim 32, Santamaria teaches parenteral, orthotopic, intradermal, subcutaneous, intramuscular, intraperitoneal, intranasal, or intravenous injection administration of the composition [0076].
Regarding claims 55-57, the claims recite the “..wherein the non-classical MHC-nanoparticle generates immunoregulatory iNKT cells that express 50%, 75% and 100% of IL-10 and/or IL-21”, Examiner notes that the limitation recites an intended result. When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. MPEP 2112.01 (I). Further, if the composition is physically the same, it must have the same properties. MPEP 2112.01 (II). Thus, the limitations “..wherein the non-classical MHC-nanoparticle generates immunoregulatory iNKT cells that express 50%, 75% and 100% of IL-10 and/or IL-21”, would naturally flow. Additionally, Santamaria teaches an antigen/MHC/co-stimulatory molecule complex operatively coupled to a nanoparticle in an amount sufficient to expand a population of antigen-specific anti-tumorigenic T cells (claims 1-2; [0005-0008]), and that the T cell is a CD8+ or a CD4+ T cell or a NKT cell [0012, 0024, 0104]. Examiner notes that the cited references render obvious claims 55-57.
Response to Arguments
Applicant's arguments filed 05/15/2026 have been fully considered but they are not persuasive.
Applicant Arguments
Applicant argues that Santamaria teaches administering antigen/MHC complexes and co- stimulatory complexes coupled to the nanoparticle core, and that the co-stimulatory molecule is required as part of the complex that is administered to the subject. Applicant argues that claim 32 recites a subsequent or further administration of antigen/MHC nanoparticle complexes, following the administration of the complexes with co-stimulatory molecules recited in claim 1 (Page 6-8 of Arguments).
Examiner’s Response
The arguments presented above have been fully considered but are unpersuasive. Examiner notes that such a nanoparticle comprising a non-classical MHC molecule and an antigen such as sphingolipid is known in the art and known to generate immunoregulatory iNKT cells. Examiner notes that Santamaria teaches an antigen/MHC/co-stimulatory molecule complex operatively coupled to a nanoparticle in an amount sufficient to expand a population of antigen-specific anti-tumorigenic T cells (claims 1-2; [0005-0008]), and that the T cell is a CD8+ or a CD4+ T cell or a NKT cell [0012, 0024, 0104]. Santamaria further teaches antigen/MHC/nanoparticle complexes without co-stimulatory molecules (claim 32; [0008, 0073]). Santamaria teaches that the antigen is a molecule that can induce an immune response [0044].
Examiner notes that Applicant’s argument that claim 32 recites a subsequent or further administration of antigen/MHC nanoparticle complexes, following the administration of the complexes with co-stimulatory molecules is unpersuasive because the instant invention is drawn to a non-classical MHC-nanoparticle (ncMHC-NP) comprising: a) a sphingolipid or an analog thereof; b) a non-classical MHC molecule; and c) a nanoparticle; wherein the sphingolipid or the analog thereof is associated with a binding groove of the non-classical MHC molecule, and wherein the non-classical MHC molecule is coupled to the nanoparticle and wherein the non-classical MHC-nanoparticle does not comprise an immune activating co-stimulatory molecule. Such a non-classical MHC-nanoparticle is rendered obvious by Santamaria since Santamaria indeed discloses an antigen/MHC/co-stimulatory molecule complex operatively coupled to a nanoparticle in an amount sufficient to expand a population of antigen-specific anti-tumorigenic T cells (claims 1-2; [0005-0008]), and that the T cell is a CD8+ or a CD4+ T cell or a NKT cell [0012, 0024, 0104]. Santamaria further teaches antigen/MHC/nanoparticle complexes without co-stimulatory molecules (claim 32; [0008, 0073]). Further, Girardi teaches similar teaching to Santamaria and teaches complexes of MHC and antigens such as sphingolipids. Specifically teaches sphingolipids such as α-GalCer in a complex or bound to non-classical MHC CD1d (Page 10679, right col., 1st paragraph). Girardi teaches that the sphingolipids are known to illicit an immune response (Page 10677, let col., line 1-36). Examiner notes the teachings of Santamaria and Girardi can be combined because they hail from the same field of study. Thus, one of ordinary skill in the art can use the antigen of Girardi in the nanoparticle of Santamaria and would have achieved a reasonable expectation of success. Obviousness does not require absolute predictability, only a reasonable expectation of success, i.e., a reasonable expectation of obtaining similar properties. See, e.g., In re O’Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988). (MPEP 2144.08 (II). The arguments are unpersuasive.
Conclusion
No claims are allowed.
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 Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MERCY H SABILA/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
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