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 .
Claim Status
Claims 1-20 are pending. Claims 1-20 are rejected.
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.
Claim(s) 1, 3, 5-6, 8-9, 11-12, 14, 16-17 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over WO2015098928A1 by Takatsu et al. in view of Li et al.; Flexible Peptide Recognition by HLA-DR Triggers Specific Autoimmune T-Cell Responses in Autoimmune Thyroiditis and Diabetes; HHS Public Access; Published in J Autoimmun January 2017; Vol. 76, pages 1-9. (cited in the IDS filed 02/01/2024) and WO 2017/112669 by Tomer et al.
Citations for refer WO2015098928A1 to the machine translation.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
The prior art discloses an “[i]nhibitor of IL-1 and TNF activities” (title) and “a method of treating diabetes, a disease state and condition characterized by insulin resistance, a decrease in the amount of functional pancreatic β-cells, hyperglycemia, hyperlipidemia, obesity, metabolic syndrome, arteriosclerosis, autoinflammatory disease and the like” (page 1).
Takatsu et al. identify cepharanthine as a suitable inhibitor in accordance with instant claims 1, 9, 16 and 20 (page 2). Regarding instant claims 5-6, 8, 11-12, and 14, the prior art discusses administration to humans and teaches that the compound may be used in combination with another active agent such as insulin (page 3).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Regarding instant claims 1 and 16, the prior art discloses a method of treating type 1 diabetes comprising administering cepharanthine to a subject but does not specify that the subject has a human leukocyte antigen class II, DR3 allele (HLA-DR3) genotype. Additionally, the prior art is silent to treating autoimmune polyglandular syndrome type 3 variant as recited in instant claims 3 and 9.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Li et al. report (title) “[f]lexible peptide recognition by HLA-DR triggers specific autoimmune t-cell responses in autoimmune thyroiditis and diabetes” and teach (page 2):
Autoimmune endocrine disorders frequently occur in the same individual. This association is referred to as autoimmune polyglandular syndrome (APS) [1]. The most common type of APS consists of the co-occurrence of autoimmune thyroid disease (AITD), in which the target endocrine gland is the thyroid, and type 1 diabetes (T1D), in which the target endocrine gland is the pancreatic islets beta cells [2–5]. The clinical phenotype of AITD +T1D within the same individual is referred to as a variant of APS type 3 (APS3v).
Tomer et al. teach (title) “[s]mall inhibitors of HLA-DR3 binding for treating auto-immune thyroiditis” and disclose cepharanthine as a compound of the invention wherein the compound may be administered to a subject in a method of treating (paragraph [0010]).
Accordingly, a person of ordinary skill treating subjects with type 1 diabetes in the method of Takatsu et al. could expect to encounter a population of subjects with concomitant thyroid disease, i.e., autoimmune polyglandular syndrome type 3 variant, as coexistence of the autoimmune endocrine disorders is frequent as taught by Li et al. A person of ordinary skill seeking to treat such patients would be motivated to administer cepharanthine which is disclosed as useful for treating type 1 diabetes by Takatsu et al. and for treating auto-immune thyroiditis by Tomer et al.
Regarding instant claims 1-2, 9-10, and 16-17, Tomer et al. state that the cepharanthine can be used for treating autoimmune thyroid diseases in a patient and suggests that it may be advantageous to screen the patient population for those patients that carry an HLA-DRβ1-Arg74 variant as it may indicate an increase in the benefit of the prior art agents to such individual patients (paragraph [0019]). Tomer et al. define HLA-DRβ1-Arg74 as the HLA-DR3 containing arginine at position 74 (paragraph [0004]).
Claim(s) 4, 15, 18 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over WO2015098928A1 by Takatsu et al. in view of Li et al.; Flexible Peptide Recognition by HLA-DR Triggers Specific Autoimmune T-Cell Responses in Autoimmune Thyroiditis and Diabetes; HHS Public Access; Published in J Autoimmun January 2017; Vol. 76, pages 1-9. (cited in the IDS filed 02/01/2024) and WO 2017/112669 by Tomer et al. as applied to claims 1, 3, 5-6, 8-9, 11-12, 14, 16-17 and 20 above, and further in view of Healthline. “What Are GAD Antibodies?” Last updated October 19, 2020. Accessed on March 17, 2026 at https://www.healthline.com/health/diabetes/gad-antibodies.
Takatsu et al., Li et al., and Tomer et al. in combination teach a method of treating type 1 diabetes in subjects with autoimmune polyglandular syndrome type 3 variant by administering cepharanthine but do not teach that the subject has high expression of serum glutamic decarboxylase antibody (GAD).
Healthline teaches that in subjects diagnosed with diabetes GAD antibody tests are used to identify the type of diabetes and that the presence of high GAD antibody levels in the subject suggests that the subject has type 1 diabetes (pages 1-3).
Accordingly, a person of ordinary skill treating subjects with diabetes in the combined method would be motivated to screen subjects for high serum GAD to determine if the subject has type 1 diabetes and would benefit from being administered cepharanthine.
Claim(s) 7 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over WO2015098928A1 by Takatsu et al. in view of Li et al.; Flexible Peptide Recognition by HLA-DR Triggers Specific Autoimmune T-Cell Responses in Autoimmune Thyroiditis and Diabetes; HHS Public Access; Published in J Autoimmun January 2017; Vol. 76, pages 1-9. (cited in the IDS filed 02/01/2024) and WO 2017/112669 by Tomer et al. as applied to claims 1, 3, 5-6, 8-9, 11-12, 14, 16-17 and 20 above, and further in view of US 20120094903 A1 by Costantino et al. (cited in the IDS filed 02/01/2024).
Takatsu et al., Li et al., and Tomer et al. in combination teach a method of treating type 1 diabetes in subjects with autoimmune polyglandular syndrome type 3 variant by administering cepharanthine and insulin but do not specify the formulation of the insulin as required by instant claims 7 and 13.
Constantino et al. teach (title) “[c]ompositions for intranasal delivery of human insulin and uses thereof” and disclose an ultra-rapid acting pharmaceutical formulation for delivery of the insulin (abstract). The prior art discloses the pharmaceutical formulation for treating type 1 diabetes (page 49, claim 96).
Accordingly, a person of ordinary skill seeking to improve therapeutic outcomes in subjects with APS3v in the combined method of Takatsu et al., Li et al., and Tomer et al. would have been motivated to administer the rapid-acting insulin formulation of Constantino et al. in addition to cepharanthine.
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.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11266642 in view of WO2015098928A1 by Takatsu et al., Li et al.; Flexible Peptide Recognition by HLA-DR Triggers Specific Autoimmune T-Cell Responses in Autoimmune Thyroiditis and Diabetes; HHS Public Access; Published in J Autoimmun January 2017; Vol. 76, pages 1-9. (cited in the IDS filed 02/01/2024), WO 2017/112669 by Tomer et al., US 20120094903 A1 by Costantino et al. (cited in the IDS filed 02/01/2024), and Healthline. “What Are GAD Antibodies?” Last updated October 19, 2020. Accessed on March 17, 2026 at https://www.healthline.com/health/diabetes/gad-antibodies.
Claim 3 of the patent discloses a method of treating thyroid disease comprising administering cepharanthine which serves as the basis of a rejection under 35 USC 103. The teachings and rationale of Takatsu et al., Li et al., Tomer et al., Constantino et al. and Healthline relative to instant claims 1-20 are incorporated here by reference. The instant claims are deemed to be variants of the subject matter of the patent for the same reasons as under 35 USC 103.
Conclusion
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/A.A.C./Examiner, Art Unit 1626
/MATTHEW P COUGHLIN/Primary Examiner, Art Unit 1626