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 .
DETAILED ACTION
Pursuant to the amendment dated 05/11/2026, claims 1 and 13-14 were amended, claims 2-3, 8-12, 15-17, and 21-32 were canceled, and claims 33-41 were newly added. Claims 1, 4-7, 13-14, 18-20 and 33-41 are pending in the instant application and are examined on the merits herein.
Priority
This application is a National Stage Application of PCT/US2022/015670, filed on 02/08/2022 and claims benefit of 63/147,234 filed on 02/08/2021.
Information Disclosure Statement
The information disclosure statement (IDS) dated 05/11/2026 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, the IDS document has been placed in the application file and the information therein has been considered as to the merits.
Withdrawn Rejections
Applicant’s amendment, filed on 05/11/2026, with respect to the rejection of claims 1, 4-7, 14, and 18-20 under 35 U.S.C. 112((a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement, has been fully considered and is persuasive. Applicant has amended independent claim 1 to remove the phrases “treating” and “preventing”. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 01/12/2026, with respect to the rejection of claims 1, 5-7 and 20 under 35 U.S.C. 102(a)(1) as being anticipated by Shoskes et al. (Transplantation, published 12/15/2005, IDS dated 08/08/2023) as evidenced by Escande et al. (Diabetes, published 03/13/2014, IDS dated 08/08/2023) and as evidenced by Pubchem (https://pubchem.ncbi.nlm.nih.gov/compound/quercetin, published 10/05/2020, accessed 12/02/2025, PTO-892 dated 12/09/2025), has been fully considered and is persuasive. Applicant has amended independent claim 1 to add the limitation that the small molecule CD38 inhibitor is encapsulated within an engineered nanoparticle which is not exemplified by Shoskes. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 01/12/2026, with respect to the rejection of claims 13 under 35 U.S.C. 102(a)(1) as being anticipated by Escande et al. (Diabetes, published 03/13/2014, IDS dated 08/08/2023), has been fully considered and is persuasive. Applicant has amended independent claim 13 to add the limitation that the small molecule CD38 inhibitor is encapsulated within an engineered nanoparticle which is not exemplified by Escande. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 01/12/2026, with respect to the rejection of claims 14, 18 and 19 under 35 U.S.C. 102(a)(1) as being anticipated by Gochi et al. (Transplantation Direct, published 11/10/2020, PTO-892) and by Escande et al. (Diabetes, published 03/13/2014, IDS dated 08/08/2023), has been fully considered and is persuasive. Applicant has amended independent claim 14 to add the limitation that the small molecule CD38 inhibitor is encapsulated within an engineered nanoparticle which is not exemplified by Gochi. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 01/12/2026, with respect to the rejection of claims 14, 18 and 19 under 35 U.S.C. 103 as being unpatentable over Jordan et al. (WO 2020/185672 A1, published 09/17/2020, PTO-892 dated 12/09/2025) and Shoskes et al. (Transplantation, published 12/15/2005, IDS dated 08/08/2023) and as evidenced by Escande et al. (Diabetes, published 03/13/2014, IDS dated 08/08/2023), has been fully considered and is persuasive. Applicant has amended independent claim 1 to add the limitation that the small molecule CD38 inhibitor is encapsulated within an engineered nanoparticle which is not taught by the combined teachings of Jordan and Shoskes. The rejection is hereby withdrawn.
Rejections Necessitated by Amendment
The following are new ground(s) necessitated by Applicants' amendment, filed on 05/11/2026, wherein independent claims 1, 13 and 14 were amended to alter the breadth and scope of the claim, claims 34-41 were newly added and wherein the remaining pending claims 4-7 and 18-20 depend from said independent claims 1 and 14.
New and Modified Grounds of Rejection
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.
Claims 1, 5-7, 13-14, 18-20, and 33-41 are rejected under 35 U.S.C. 103 as being unpatentable over Pranesh et al. (US 2020/0397807 A1, published 12/24/2020, PTO-892) as evidenced by Haffner et al. (J. Med. Chem., published 04/01/2015, IDS dated 02/19/2024).
Pranesh is drawn to nicotinamide riboside (NR), whether alone or in combination with one or more additional therapeutic agents, for treating mitochondrial diseases, mitochondria-related diseases and conditions, and other disorders and conditions (abstract). The other additional therapeutic agents may be CD38 inhibitors such as thazoloquin(az)olin(on)es such as 78c (paragraph 0275). As evidenced by Haffner, 78c meets the limitation of instant formula I wherein X is NR1 when R1 is an unsubstituted alkyl, R2 is an oxo group, R4 is -NR10R11 when R10 is a substituted cycloalkyl and R11 is a hydrogen, R7 is an unsubstituted heteroaryl, and R3, R5, R7 and R8 are hydrogen (Table 4).
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CD38 inhibitor 78c (Molecular weight 413.53 g/mol).
Pranesh teaches that due to their cytoprotective properties, NR and NAR derivatives can promote donor graft preservation in organ transplantation. Therefore, the NR and derivatives can be applied to cells, tissue or organ employed in transplantation and cell therapies, such as solid-tissue grafts, organ transplants, cell suspensions, stem cells and bone marrow cells. The cells, tissue or organ can be treated with one or more NR/NAR derivatives prior to, concurrently with or/and post administration/implantation of the cells, tissue or organ into a recipient. The cells, tissue or organ can be treated with one or more NR/NAR derivatives prior to removal of the cells, tissue or organ from the donor, ex vivo after removal of the cells, tissue or organ from the donor, or post administration/ implantation into the recipient. For example, the donor or/and the recipient can be treated systemically with one or more NR/NAR derivatives, or can have a subset of cells, tissue or organ treated locally with one or more NR/NAR derivatives. In certain embodiments, the cells, tissue or organ (or the donor or/and the recipient) are treated with an additional therapeutic agent that prolongs graft survival, such as an immunosuppressant, a cytokine or an angiogenic factor, or any combination thereof (paragraph 0254). Pranesh teaches that inhibition of CD38 increases NAD+ levels and thereby improves mitochondrial and cellular function and increases the activity of sirtuins such as SIRTI and SIRT3 (paragraph 0275). Pranesh teaches the use of NR and at least one other therapeutic agent such as a CD38 inhibitor for an ex vivo therapy such as for organ transplantation (embodiments 60-61, page 91). The NR with one or more other therapeutic agents can be administered to the donor or/and recipient to promote liver regeneration for various clinical scenarios. Such clinical scenarios include prevention of liver decompensation in the donor or/and the recipient following liver segment/mass resection, prevention of liver failure in a recipient of a split liver or living donor transplantation where a sub-optimal liver mass is transplanted, and prevention of liver-related morbidity in the donor of a living donor transplantation (paragraph 0255). The composition may be formulated as a sustained-release composition as a nanoparticle composed of a dendrimer (e.g., a PAMAM or/and PEG dendrimer) and encapsulating an NR or NAR derivative. The dendrimer (e.g., the surface of a nanoparticle composed of a dendrimer) can optionally have or bear one or more moieties for targeting to specific organ(s), tissue(s), cell type(s) or organelle(s), such as one or more N-acetylgalactosamine (GalNAc) moieties for targeting to the liver for treatment of, e.g., a liver or metabolic disorder (paragraph 0199). The nanoparticle may be formulated with a blend of a polymeric material such as PEG or PLGA (paragraph 0208).
Pranesh does not exemplify the administration of a CD38 inhibitor as the additional one or more therapeutics. Pranesh does not exemplify the composition encapsulated in a nanoparticle.
It would have been prima facie obvious before the effective filing date to select a CD38 inhibitor such as 78c as the one or more therapeutic agent and to encapsulate the composition in an engineered nanoparticle to administer to a subject or ex vivo to improve organ survival as taught by Pranesh to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to select a CD38 inhibitor such as 78c as the one or more therapeutic agents and to encapsulate the composition in an engineered nanoparticle to administer to a subject or ex vivo to improve organ survival because Pranesh teaches that the composition may comprise an additional therapeutic such as a CD38 inhibitor such as 78c and teaches that CD38 inhibitors increase NAD+ levels and improves mitochondrial and cellular function, and that the compositions may be formulated as a sustained-release composition as a nanoparticle. One of ordinary skill in the art would have a reasonable expectation of success because Pranesh teaches administering an additional therapeutic such as CD38 inhibitor 78c ex vivo or to a subject that is undergoing a liver transplant and that the composition may be formulated as a sustained-release composition as a nanoparticle.
Regarding instant claim 13, it would have been prima facie obvious before the effective filing date to select a CD38 inhibitor such as 78c as the one or more therapeutic agent and to encapsulate the composition in an engineered nanoparticle to contact a cell expressing CD38 as taught by Pranesh to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to select a CD38 inhibitor such as 78c as the one or more therapeutic agents and to encapsulate the composition in an engineered nanoparticle to contact a cell expressing CD38 because Pranesh teaches that the composition may comprise an additional therapeutic such as a CD38 inhibitor such as 78c and teaches that CD38 inhibitors increase NAD+ levels and improves mitochondrial and cellular function, and that the compositions may be formulated as a sustained-release composition as a nanoparticle. One of ordinary skill in the art would have a reasonable expectation of success because Pranesh teaches administering an additional therapeutic such as CD38 inhibitor 78c to cells such as stem cells and that the composition may be formulated as a sustained-release composition as a nanoparticle.
Regarding instant claims 33, 34, 37, 39, and 40, it would have been prima facie before the effective filing date to select GalNAc, PEG, and PLGA to create a nanoparticle to encompasses the composition as taught by Pranesh to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to select GalNAc, PEG, and PLGA because Pranesh teaches the nanoparticle may be formulated with a blend of a polymeric material such as PEG or PLGA, and that the nanoparticle may have GalNAc on the surface to target a specific organ such as the liver. One of ordinary skill in the art would have a reasonable expectation of success because Pranesh teaches the nanoparticle may be formulated with a blend of a polymeric material such as PEG or PLGA, and that the nanoparticle may have GalNAc on the surface to target a specific organ such as the liver.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Pranesh et al. (US 2020/0397807 Al, published 12/24/2020, PTO-892) as applied to claim 1 above, and further in view of Jordan et al. (WO 2020/185672 A1, published 09/17/2020, see PTO-892).
Claim 1 is discussed above.
The teachings of Pranesh are discussed above.
Pranesh does not teach that the recipient is resistant or has acquired resistance to immunosuppressive treatment with one or more of eculizumab, thymoglobulin, bortezomib, carfilzomib, basiliximab, mycophenolate mofetil, tacrolimus, or corticosteroids.
Jordan is drawn to the use of anti-CD38 agents for desensitization and treatment of antibody-mediated rejection of organ transplants (title). Jordan teaches methods for desensitizing a human leukocyte antigen (HLA) sensitized subject to prepare for an organ transplant with an improved transplant survival and function, and/or treating or reducing the likelihood of antibody mediated rejection (ABMR) of an organ transplant in a subject, generally including administering an effective amount of an anti-CD38 antibody or a CD38-targeting therapy to reduce the symptoms or ABMR or HLA levels. The subject in the methods may have developed or is experiencing drug-resistant sensitization, and to whom standard techniques like intravenous immunoglobulin and plasmapheresis are ineffective (abstract). The subject can be one who is further resistant or has acquired resistance to immunosuppressive treatment with one or more of eculizumab, thymoglobulin, bortezomib, carfilzomib, basiliximab, mycophenolate mofetil, tacrolimus and corticosteroids (paragraph 0019).
It would have been prima facie obvious to combine the teachings of Pranesh and Jordan before the effective filing date of the claimed invention by applying the method of administering a composition comprising CD38 inhibitor 78c encapsulated in a nanoparticle as taught by Panesh to a subject that is resistant or has acquired resistance to immunosuppressive treatment as taught by Jordan to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to apply the method of administering a composition comprising CD38 inhibitor 78c encapsulated in a nanoparticle as taught by Panesh to a subject that is resistant or has acquired resistance to immunosuppressive treatment because Jordan teaches that CD38 inhibitors may be used for desensitization and treatment of antibody-mediated rejection of organ transplants. One of ordinary skill in the art would have a reasonable expectation of success because Pranesh teaches that 78c is a CD38 inhibitor and may be administration to reduce transplant rejection and Jordan teaches that CD38-targeting therapy can be used for reducing the likelihood of antibody mediated rejection (ABMR) of an organ transplant in a subject including wherein the subject is resistant or has acquired resistance to immunosuppressive treatment.
Response to Arguments
Applicant's arguments filed 05/11/2026 have been fully considered in so much as they apply to the amended claims but they are not persuasive.
Applicant argues that Jordan fails to disclose or suggest an effective amount of the small molecule CD38 inhibitor encapsulated within an engineered nanoparticle, as claimed. The argument is unpersuasive. In the new office action, Jordan is not relied upon to teach a small molecule CD38 inhibitor that is encapsulated within an engineered nanoparticle, but rather that CD38 inhibitors may be used for desensitization and treatment of antibody-mediated rejection of organ transplants. Pranesh is relied upon to teach administration of a small molecule CD38 inhibitor such as 78c that may be encapsulated in an engineered nanoparticle to a subject undergoing an organ transplant.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/S.L.S./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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