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 .
It is noted to applicants that the examiner made an inadvertent error in the Office Action mailed on 9/8/2025 and the examiner is sorry for any inconvenience it may have caused. Therefore, the previous office action of 9/8/2025 is being vacated, and a new office action has been set forth below.
Claims 21-32 are pending and under examination.
Information Disclosure Statement
The Information Disclosure Statement filed on 3/21/2023 has been considered.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 21-32 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The written description in this case is not commensurate in scope with “a pharmaceutical composition in the form of an injectable aqueous solution, the pH of which is from 3.0-4.4, comprising pramlintide and rapid acting insulin lispro A21G”.
The claims broadly encompass any concentration of insulin lispro 21G and any concentration of pramlintide in the claimed injectable aqueous solution at pH range 3.0-4.4. The claims do not require that require that insulin lispro 21G and pramlintide be present in a certain ratio and amount, or concentration to be effective for the intended use in the treatment of diabetes (see claims 28-32).
The specification on pg.22-26 (Examples 1-3), discloses that insulin lispro A21G 100U/ml (3.5 mg/mL) and pramlintide 0.6 mg/mL is prepared that comprises m-cresol (25 mM), glycerol (184 mM) and acetic acid buffer (18 mM) at acidic pH 3.8. To provide adequate written description and evidence of possession of a claimed invention, the specification must provide sufficient distinguishing feature of the claimed composition. Some of the factual considerations that are weighed when determining a written description include the level of skill and knowledge in the art, the disclosure of complete or partial structures, the disclosure of physical and or chemical properties, adequate disclosure of the functional characteristics, the correlation between structure and function, and disclosure of methods of making.
In the instant case, the specification at pg.22-26 (Examples 1-3), only adequately discloses making insulin lispro A21G 100U/ml (3.5 mg/mL) and pramlintide 0.6 mg/mL. Claim 24 recites A21G lispro about 2-20 mg and claim 26 recites to use pramlintide about 0.32-5 mg/ml for the composition. Maikawa et al. (IDS, Nature Biomed. Engineering vol. 4, 507-517, 2020) teaches making a co-formulation of stabilized insulin and pramlintide that enhances mealtime glucagon suppression in diabetic pigs. Maikawa et al. teach that most of the insulin formulation are stable around pH 7.4 and pramlintide formulations are stable in acidic pH around 4. Maikawa et al. uses stabilizing excipient CB(7) with PEG to reduce aggregation of insulin and pramlintide formulations (pg. 509, left col.). Chan (WO 2019020820) teaches making a composition comprising human insulin glargine (human insulin A21G, B31R, B32R) and pramlintide at pH 3.5-4.4 (abstract). WO 2019020820 teaches that substitution of A21G, B28D des B30 or A21G, B28E desB30 is soluble at an acidic pH [00019]. WO 2019020820 teaches that human insulin A21G is 240-3000 uM or 40-500 U/mL. The specification does not describe that the concentration of A21G lispro and pramlintide can be any amount and any ratio. The specification does not disclose a range of human A21G lispro and pramlintide ratio that can be soluble and stable for injectable aqueous composition. The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed.
Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, 1 "Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.
Vas-Cath Inc. V. Mahurka, 19 USPQ2d 1111, states that applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention, for purposes of the written description inquiry, is whatever is now claimed (see page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (see Vas-Cath at page 1116).
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B (1), the court states an adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.
As discussed above, the skilled artisan cannot envision the detailed invention of “a pharmaceutical composition in the form of an injectable aqueous solution, the pH of which is from 3.0-4.4, comprising any amount of pramlintide and any amount of rapid acting insulin lispro A21G ” and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of making a mutation. The compound itself is required. See Fiers v.Revel, 25USPQ2d 1601 at 1606 (CAFC 1993) and Amgen v.Baird, 30 Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 148 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class.
Therefore, the full breadth of the claims do not meet the written description provision of 35 U.S.C. §112, first paragraph.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision (see page 1115).
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.
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) 21-32 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019020820 (IDS, Chan You-Ping) in view of WO 2015044922 (IDS, Sahib et al.).
The instantly claimed invention is broadly drawn to a pharmaceutical composition in the form of an injectable aqueous solution, the pH of which is from 3.0 to 4.4, comprising pramlintide and a rapid-acting insulin analog insulin lispro A2IG ( human insulin A21G, B28K,B29P), wherein the composition is free of zinc (claim 22), wherein the composition comprises nicotinamide (claim 23), wherein the composition comprises insulin lispro A21G from 2-20 mg/ml (claims24-25), wherein the composition comprises pramlintide from 0.32 to 5 mg/ml (claim 26), wherein the pH of the solution is 3.7 to 4.3 (claim 27). Claims 28-32 are drawn to intended use of the composition and how to administer the composition to a subject.
WO 2019020820 teaches a composition comprising human insulin A21G about 100 U/mL as well as pramlintide at 0.6 mg/ml to 1.0 mg/ml and the composition does not comprise zinc (Table 1). The composition comprises pH of 4.0. WO 2019020820 teaches that formulation at pH 3.5 to 4.4 has pharmacokinetic properties capable with use at mealtimes and allows better control of postprandial glycemia [00028]. WO 2019020820 teaches that composition in the form of an injectable solution, the pH which is between 3.5 and 4.4, comprising at least human insulin A21G and a glucagon suppressor, in particular with prandial action, provides improved control of postprandial glycemia [00031]. WO 2019020820 teaches that the composition is to provide physical and chemical stability for at least two weeks to one month at 30 °C and at least one year to two years at 5°C [00041]. Regarding claims 24-26, WO 2019020820 teaches that human insulin A21G is 40 to 500 U/ml [00069] and pramlintide is from 0.32 to 5 mg/ml. WO 2019020820 teaches that the composition comprises at least one absorption promoter, wherein the absorption promoter can be nicotinic agents such as nicotinamides [000134-000135]. WO 2019020820 teaches that the composition is for treating diabetes and to improve postprandial glycemia (see claims 17-20) and that the composition is to be administered as a bolus before meal (claim 17). WO 2019020820 does not teach using human insulin A21G lispro in the composition.
Sahib et al teach that insulin analogs or derivative having isoelectric point between 4.0 to 5.7 comprises recombinant human insulin, insulin NPH, insulin lispro, insulin aspart, A21G insulin, A21G B28Lys insulin, A21GB28Lys, B29Pro (which is A21G lispro), A21G B28Asp or Viagject (rapid acting insulin).
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 A21G B28Lys, B29Pro (lispro) as taught by Sahib et al that A21G human insulin lispro iso electric pH is between 4 to 5.7 to substitute A21G human insulin in the composition comprising A21G human insulin and pramlintide as taught by WO 2019020820. Additionally, one would have been motivated to do so because Sahib et al teach that A21G lispro human insulin comprises isoelectric pH between 4 and 5.7 and would be stable in acidic pH. Further, one would have a reasonable expectation of success in using human lispro A21G in the composition taught by WO 2019020820 because Sahib et al teaches that human lispro A21G comprises isoelectric pH in between 4 and 5.7.
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 21-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 21-32 of copending Application No. 17/928,502 in view of Homko et al (Diabetes Care 26: 2027-2031, 2003) or Sahib et al.
Claims 21-32 of US Application No.17/928,502 broadly teach a pharmaceutical composition in the form of an injectable aqueous solution, the pH of which is from 3.0 to 4.0, comprising pramlintide and a rapid-acting insulin analog is insulin aspart A21G, also called human insulin A21G,B28D (claims 21), wherein said claim is free of zinc (claim 22),.wherein it comprises nicotinamide (claim 23), wherein the concentration of insulin aspart A21 G is from 2 to 20 mg/mL (claim 24), wherein the concentration of insulin aspart A21 G is 3.5 mg/mL (claim 25), wherein the concentration of pramlintide is from 0.32 to 5 mg/mL (claim 26), wherein the pH of the solution is from 3.2 to 3.8 (claim 27). The pharmaceutical composition according to claim 21, for use in the treatment of diabetes, wherein it is administered as one or several boluses at mealtime (claim 28). The pharmaceutical composition- according to claim 21, for use in the treatment of diabetes, wherein it is administered using a pump (claim 29). The pharmaceutical composition according to claim 21, for use in the treatment of diabetes, wherein it is administered to improve the control of postprandial glycemia (claim 30). The pharmaceutical composition according to claim 21, for use in the treatment of diabetes, wherein it is administered to improve the control of postprandial glycemia and to decrease the adverse effects of pramlintide (claim 31). The pharmaceutical composition according to claim 21, for use in the treatment of diabetes, wherein it enables to decrease the food consumption induced by insulin (claim 32). The teachings of claims 21-32 of the US Application No.17/928,502 are similar or identical to the instant claims 21-32, except insulin molecule which is lispro (A21G , B28K, B29P) instead of insulin aspart.
Homko et al teach that the insulin aspart and insulin lispro are similar in that both are fast acting insulin and administered subcutaneously near meal time (see Figure 1 and Figure 2A-C). Both insulin produced similar serum insulin levels (250-300 pmol/l) at about 30 min (abstract). They state that they found no significant difference comparing actions of both analogs (see conclusion, pg. 2030, (comparison of insulin actions)).
Sahib et al teach that insulin analogs or derivative having isoelectric point between 4.0 to 5.7 comprises recombinant human insulin, insulin NPH, insulin lispro, insulin aspart, A21G insulin, A21G B28Lys insulin, A21GB28Lys, B29Pro (which is A21G lispro), A21G B28Asp or Viagject (rapid acting insulin).
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 aspart insulin to substitute with insulin lispro as taught by Homko et al or Sahib et al. as both insulins have similar action profile and have isoelectric point between 4.0 5.7. Additionally, one would have been motivated to do so because insulin aspart and insulin lispro have similar mode of action and the modification is well known in the art and as taught by Homko et al. Further, one would have a reasonable expectation of success in using insulin aspart and insulin lispro interchangeably because Homko et al teach that they did not find any significant difference in both insulins (conclusion).
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674