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 .
Applicant’s response filed on 1/29/2026 is acknowledged and fully considered.
Status of Application, Amendments, And/Or Claims
The amendments of claims 1, and 11-12 have been made of record.
Claims 1-13 are pending.
Claim 13 remain withdrawn for being drawn to a non-elected invention on record.
Claims 1-12 are under examination.
Response to Arguments
Claim Rejections - 35 USC § 112--withdrawn
The rejection of claim 11 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of applicant’s amendments to the claim which now depends from claim 10.
Claim Rejections - 35 USC § 102-maintained
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Balschmidt et al. (US Pub. No. 2010/0120660) for the reasons of record at pg. 3 of the office action of 8/12/2025 and as discussed below.
The instantly claimed invention is broadly drawn to a composition comprising: An insulin-divalent cation complex in which insulin is charged with a plurality of divalent cations selected from the group consisting of zinc, calcium, and magnesium in a ratio of said insulin molecule to said divalent cation that is sufficient to permit insulin to be bioavailable in therapeutically effective quantities, wherein the insulin is pre-treated with hydrochloric acid (HCl);wherein the insulin is chelated with ethylenediaminetetraacetic acid (EDTA) after treatment with the HCl; and wherein the resulting compound is a cation-charged insulin compound suitable for oral administration.
Balschmidt et al teach making an aqueous pharmaceutical composition comprising small amount of zinc and insulin [0189]. They teach that insulin can be 2, 3 4 or zinc ions per insulin hexamer. They teach that most commercial insulin formulation marketed comprises zinc to enhance stability of insulin that amount of zinc is 2-4 ions per hexamer insulin [0190]. Therefore, the instantly claimed invention is implicitly or explicitly anticipated by the claimed invention.
Claim(s) 1, 10 and 12 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Feldmeier, Hans-Georg (DD 290134 published on 5/23/1991) for the reasons of record at pg. 4 of the office action of 8/12/2025, and as discussed below.
The instant invention is broadly drawn to a composition comprising: An insulin-zinc complex in which insulin is charged with a plurality of zinc ions that are bound in a ratio of said insulin molecule to said zinc ions that is sufficient to permit insulin to be bioavailable in therapeutically effective quantities; insulin is pre-treated with hydrochloric acid (HCl);wherein the insulin is chelated with ethylenediaminetetraacetic acid (EDTA) after treatment with the HCl; wherein the resulting compound is a cation-charged insulin compound suitable for oral administration; and wherein hydrochloric acid in a concentration sufficient to permit said insulin-zinc complex to be dissolved in aqueous solution.
Feldmeier, Hans-Georg teach a composition comprising porcine insulin containing from 3-3.4% zinc chloride and hydrochloric acid that contains 1.3 times of 1M hydrochloric acid (claims). Therefore, the instantly claimed inventions is implicitly or explicitly anticipated.
Applicants argue that Balschmidt et al teach an insulin solution obtained by freeze-drying or spray-drying the insulin and subsequently re-dissolving in water. They argue that the insulin composition of Balschmidt comprises only 2-4 zinc ions per insulin hexamer. They argue that the specification discloses making insulin composition wherein molar ratio of insulin to zinc is 1:30 to 1:300. They argue that Balschmidt et al teach chelating agent in the composition but they do not teach use of chelating agent in the process. They argue that Feldmeier teaches making crystalline suspension of insulin as compared with cation-charged insulin of the instant invention.
Applicant’s arguments have been fully considered but they are not persuasive because the amended claim is drawn to product by process but if the product is same then the process does not carry any patentable because a product can be made using a different process. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., insulin to zinc ratio is 1:30 to 1:300) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
"[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted) (Claim was directed to a novolac color developer. The process of making the developer was allowed. The difference between the inventive process and the prior art was the addition of metal oxide and carboxylic acid as separate ingredients instead of adding the more expensive pre-reacted metal carboxylate. The product-by-process claim was rejected because the end product, in both the prior art and the allowed process, ends up containing metal carboxylate. The fact that the metal carboxylate is not directly added, but is instead produced in-situ does not change the end product.). Furthermore, "[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes." Amgen Inc. v. F. Hoffmann-La Roche Ltd., 580 F.3d 1340, 1370 n. 14, 92 USPQ2d 1289, 1312, n. 14 (Fed. Cir. 2009). See also Biogen MA Inc. v. EMD Serono, Inc., 976 F.3d 1326, 1334, 2020 USPQ2d 11129 (Fed. Cir. 2020) ("Biogen is certainly correct that the scope of composition and method of treatment claims is generally subject to distinctly different analyses. But where, as here, the novelty of the method of administration rests wholly on the novelty of the composition administered, which in turn rests on the novelty of the source limitation, the Amgen analysis will necessarily result in the same conclusion on anticipation for both forms of claims."); United Therapeutics Corp. v Liquidia Techs., Inc., 74 F.4th 1360, 1373, 2023 USPQ2d 862 (Fed. Cir. 2023) (the court held that product-by-process claims were properly rejected as "anticipated by a disclosure of the same product irrespective of the processes by which they are made."); and Purdue Pharma v. Epic Pharma, 811 F.3d 1345, 117 USPQ2d 1733 (Fed. Cir. 2016). However, in the context of an infringement analysis, a product-by-process claim is only infringed by a product made by the process recited in the claim. Id. at 1370 ("a product in the prior art made by a different process can anticipate a product-by-process claim, but an accused product made by a different process cannot infringe a product-by-process claim").
Claim Rejections - 35 USC § 103-maintained
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.
Claim(s) 1, 5-9 remain rejected under 35 U.S.C. 103 as being unpatentable over Balschmidt et al. (US Pub. No. 2010/0120660) in view of Yang (CN 101912600) as evidenced by Traverso et al. (WO 2018089684, also published as US Pup. No. 20220193240) for the reasons of record at pg. 4-6 of the office action of 8/12/2025, and as discussed below.
Claim(s) 1, and 10-11 remain rejected under 35 U.S.C. 103 as being unpatentable over Balschmidt et al. (US Pub. No. 2010/0120660) in view of Yang (CN 101912600, pub. Date1/29/2014) for the reasons of record at pg.6-9 of the office action of 8/12/2025 and as discussed below.
The instantly claimed invention is broadly drawn to a composition comprising: An insulin-divalent cation complex in which insulin is charged with a plurality of divalent cations selected from the group consisting of zinc, calcium, and magnesium in a ratio of said insulin molecule to said divalent cation that is sufficient to permit insulin to be bioavailable in therapeutically effective quantities, wherein insulin is pre-treated with hydrochloric acid (HCl);wherein the insulin is chelated with ethylenediaminetetraacetic acid (EDTA) after treatment with the HCl; and wherein the resulting compound is a cation-charged insulin compound suitable for oral administration, the composition of claim 1 comprising a chelating agent where the concentration of chelating agent is sufficient to remove surface ions off the insulin molecule (claim 5), wherein the chelating agent concentration is 5mM to 10mM (claim 6), wherein the chelating agent is ethylenediaminetetraacetic acid (EDTA) (claim 7), wherein the chelating agent is egtazic acid (claim 8), and wherein the chelating agent is dimercaptosuccinic acid.
Balschmidt et al teach making an aqueous pharmaceutical composition comprising small amount of zinc and insulin [0189]. They teach that insulin can be 2, 3 4 or zinc ions per insulin hexamer. They teach that most commercial insulin formulation marketed comprises zinc to enhance stability of insulin that amount of zinc is 2-4 ions per hexamer insulin [0190]. Balschmidt et al do not teach that the insulin composition comprises a chelating agent, wherein the chelating agent is about 5 mM to about 10 mM of EDTA, egtazic acid or dimercaptosuccinic acid.
Yang teaches an insulin composition comprising zinc containing insulin and zinc chelating agent, wherein the chelating agent is EDTA (claim 6 and 13).
Traverso et al. teach that a chelating agent can be used to reduce divalent ions or reduce ionic bond (see paragraph [0078]), and that such agents include EDTA, dimercaptosuccinic acid, egtazic acid (see paragraph [0077]). They teach that the concentration of such agent is greater than 1 mM or greater, equal to 5 mM or greater than or equal to 10 mM (see paragraph [0081]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use a chelating agent e.g., EDTA as taught by Yang or a functionally equivalent chelating agent such as dimercaptosuccinic acid, egtazic acid as taught by Traverso et al to make an insulin composition as taught by Balschmidt et al.
Additionally, one would have been motivated to do so because Traverso et al teach using a chelating agent such as EDTA, dimercaptosuccinic acid, or egtazic for renaturation buffer for dimeric proteins (abstract). Further, one would have a reasonable expectation of success in using a chelating agent from EDTA, dimercaptosuccinic acid, or egtazic acid well known in the art.
Applicants argue that Yang does not teach EDTA in claims 5-6 and 12-13. They argue that Yang teach that a zinc chelating agent can be EDTA, however Yang fails to treat insulin with HCl prior to treating with EDTA. They teach that Traverso teaches EDTA in different way than the instant teaching in the specification.
Applicants’ arguments have been fully considered and the teaching of Yang has been corrected to that Yang teaches EDTA in claims 6 and 13. Applicants’ arguments that Yang fails to teat insulin with HCl and Traverso teaches EDTA in different way than the instantly claim, 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).
Double Patenting-maintained
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 1-4 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,478,534 (the ‘534)for the reasons of record and as discussed below. Although the claims at issue are not identical, they are not patentably distinct from each other because a composition comprising an insulin-divalent cation from the group zinc, calcium or Magnesium, wherein the cation is zinc and the ratio of insulin zinc is 1:38 to approx.. 1:238, or 1: 60 to approx. 1:300, or 1:80 to approx. 1:300 is taught in claims 1-4 of U.S. Patent No. 11,478,534 .
Applicants argue that the instant claims are different from those of the ‘534 patent with zinc ion bound to the surface of an insulin molecule in a ratio of 1:137, and the intended purpose of composition is for oral administration.
Applicants’ arguments have been fully considered but the amended claims 1-4 are broadly drawn to a composition comprising: An insulin-divalent cation complex in which insulin is charged with a plurality of divalent cations selected from the group consisting of zinc, calcium, and magnesium in a ratio of said insulin molecule to said divalent cation that is about 1:38 to 1:238, 1:60 to 1:300, or 1:80 to 1:300 which are taught by claim 1 of US Pat. No. ‘534. Although applicants have made amendments to claim 1 that is drawn to a product by process, claims are still anticipated by claim 1 of the US Pat. No. ‘534. Therefore, the rejection is maintained.
Conclusion
No claim is 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.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674