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
Election/Restrictions
Applicant's election with traverse of Group I; A14E, B16H, B25H, B29K (N(e)-docosanedioyl-gGlu-12xOEG), desB30 human insulin (i.e. insulin icodec); and N-ε26-|2-(2-|2-(2-|2-(2-[4-(21-carboxyheneicosanoylamino)-4(S)-carboxybutanoylamino]ethoxy)ethoxy]acetylamino)ethoxy]ethoxy)acetyl] [Gly8, Arg34] GLP-1-(7-37) peptide (i.e. Orforglipron; LY3502970) in the reply filed on 7/21/2026 is acknowledged. The traversal is on the ground(s) that searching and examining claims 10-18 and 24-35 together would not impose an undue burden on the Examiner. This is not found persuasive because for the national stage applications filed under 35 USC 371, the applicable standard for restriction is 37 CFR 1.499, where lack of unity is required for restriction. This regulation is silent on search burden. For national applications filed under 35 USC 111(a), the applicable standard is 37 CFR 1.141-1.146, where the criteria is excessive examiner search burden. As applicants have stated on their application data sheet and on their declaration that this application was filed under 35 USC 371, search burden is not the proper criteria for restriction of this application.
The requirement is still deemed proper and is therefore made FINAL.
Claims 17-18, 24, 31 and 35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species/invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 7/21/2026.
Status of the Claims
Claims 10-18 and 24-35 are pending in this application.
Claims 13, 17-18, 24, 31 and 35 are withdrawn from consideration as being drawn to a non-elected species/invention.
Claims 10-12, 14-16, 25-30 and 32-34 are presently under consideration as being drawn to the elected species/invention.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 10-12, 14-16, 25-30 and 32-34 are rejected 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 10 recites the broad recitation “q is an integer of 0 or from 1 to 10”, and the claim also recites “Acy, L1, and L2 are linked by amide bonds” (i.e. q must be at least 1) which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 11-12, 14-16, 25-30 and 32-34, which depend from claim 10, are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as these claims incorporate by dependency the indefiniteness of claim 10.
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 10-12, 14-16, 25-30 and 32-34 are rejected under 35 U.S.C. 103 as being unpatentable over Norrman (WO 2018/109162) in view of Madsen et al. (EP2049149B1).
With respect to claims 10 and 14-15, Norrman teaches a pharmaceutical composition comprising an insulin derivative which is:
1) A14E, B16H, B25H, B29K((NE-Eicosanedioyl-gGlu-[2-(2-{2-[2-(2-aminoethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl)), desB30 human insulin (Compound 1) (claim 1);
2) A14E, B16H, B25H, B29K(NE-Hexadecandioyl-gGlu), desB30 human insulin (Compound 2) (claim 2);
3) A14E, B16H, B25H, B29K(NE-Eicosanedioyl-gGlu), desB30 human insulin (Compound 3) (claim 3); and
4) A14E, B25H, desB27, B29K(NE-Octadecandioyl-gGlu), desB30 human 30 insulin (Compound 4) (claim 4),
and further comprising the insulinotropic GLP-1 compound semaglutide (claim 43).
Norrman also teaches that semaglutide can be described by the structure Aib8, Lys26(OEG-OEG-γ-Glu-C18-diacid), Arg34) GLP-1 H(7-37)-OH, which can also be called (N-ε26-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butyrylamino]ethoxy}ethyl Oxy)acetylamino]ethoxy}ethoxy)-acetyl][Aib8, Arg34]GLP-1-(7-37) (page 3, 3rd para), which corresponds to instant formula (B), where r is 1, q is 0, and G1 is GLP-1-(7-37).
Norrman does not teach that the insulin derivative is PEGylated.
Madsen et al. teach similar insulin derivatives that are PEGylated (claims 1-15).
Madsen et al. also teach that “[t]he PEGylated, extended insulins have higher bioavailability and a longer time-action profile than regular insulin and are in particular suited for pulmonary administration. They will also have a high physical stability and a low tendency to fibrillation and will be soluble at neutral pH” (para [0001]).
Madsen et al. further teach that examples of PEG residues include mdPEG12 (para [0129]).
It would have been obvious to one of ordinary skill in the art to PEGylate the insulin derivatives of Norman with mdPEG12 in order to obtain insulin derivatives with higher bioavailability, longer time-action profile, high physical stability, low tendency to fibrillation, and soluble at neutral pH.
With respect to claims 11-12, as discussed above, semaglutide corresponds to instant formula (B), where r is 1, q is 0, and G1 is GLP-1-(7-37).
With respect to claim 16, Norrman teaches that the concentration of the insulin derivative is 4.2mM (claim 7).
With respect to claim 25, semaglutide corresponds to the claimed compound wherein W2 is gGlu.
With respect to claim 26, it is noted that semaglutide has an acyl moiety linked to an e amino group of the lysine of the insulin parent.
With respect to claims 27-30 and 32-34, Norman teaches 0.3, 0.4, 0.49, or 0.6 mM semaglutide; and 4.2 mM compound 1 (Table 11), which encompass the claimed ratios.
With respect to the elected species A14E, B16H, B25H, B29K (N(e)-docosanedioyl-gGlu-12xOEG), desB30 human insulin, the MPEP 2144.09 states that “[C]ompounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.)”.
Therefore, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to modify the Eicosanedioyl, Hexadecandioyl, Eicosanedioyl, or Octadecandioyl group of the insulin derivative obvious over Norrman and Madsen et al., thus arriving at the instantly claimed species A14E, B16H, B25H, B29K (N(e)-docosanedioyl-gGlu-12xOEG), desB30 human insulin.
Claims 10-12, 14-16, 25-30 and 32-34 are rejected under 35 U.S.C. 103 as being unpatentable over Norrman (WO 2018/109162) in view of Rosenstock et al. (N Engl J Med 2020;383:2107-2116).
With respect to claims 10 and 14-15, Norrman teaches a pharmaceutical composition comprising an insulin derivative which is:
1) A14E, B16H, B25H, B29K((NE-Eicosanedioyl-gGlu-[2-(2-{2-[2-(2-aminoethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl)), desB30 human insulin (Compound 1) (claim 1);
2) A14E, B16H, B25H, B29K(NE-Hexadecandioyl-gGlu), desB30 human insulin (Compound 2) (claim 2);
3) A14E, B16H, B25H, B29K(NE-Eicosanedioyl-gGlu), desB30 human insulin (Compound 3) (claim 3); and
4) A14E, B25H, desB27, B29K(NE-Octadecandioyl-gGlu), desB30 human 30 insulin (Compound 4) (claim 4),
and further comprising the insulinotropic GLP-1 compound semaglutide (claim 43).
Norrman also teaches that semaglutide can be described by the structure Aib8, Lys26(OEG-OEG-γ-Glu-C18-diacid), Arg34) GLP-1 H(7-37)-OH, which can also be called (N-ε26-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butyrylamino]ethoxy}ethyl Oxy)acetylamino]ethoxy}ethoxy)-acetyl][Aib8, Arg34]GLP-1-(7-37) (page 3, 3rd para), which corresponds to instant formula (B), where r is 1, q is 0, and G1 is GLP-1-(7-37).
Norrman further teaches that the pharmaceutical composition is for the treatment of type 2 diabetes (page 9, lines 19-23).
Norrman does not teach the elected insulin derivative (i.e. Insulin icodec).
Rosenstock et al. teach Insulin icodec for the treatment of type 2 diabetes (abstract; passim).
The MPEP 2144.06 states that it is obvious to substitute equivalents known for the same purpose.
In the instant case, it would have been obvious to substitute the insulin derivative of Norrman for the insulin derivative of Rosenstock et al.
With respect to claims 11-12, as discussed above, semaglutide corresponds to instant formula (B), where r is 1, q is 0, and G1 is GLP-1-(7-37).
With respect to claim 16, Norrman teaches that the concentration of the insulin derivative is 4.2mM (claim 7).
With respect to claim 25, semaglutide corresponds to the claimed compound wherein W2 is gGlu.
With respect to claim 26, it is noted that semaglutide has an acyl moiety linked to an e amino group of the lysine of the insulin parent.
With respect to claims 27-30 and 32-34, Norman teaches 0.3, 0.4, 0.49, or 0.6 mM semaglutide; and 4.2 mM compound 1 (Table 11), which encompass the claimed ratios.
Claims 10-12, 14-16, 25-30 and 32-34 are rejected under 35 U.S.C. 103 as being unpatentable over Norrman (WO 2018/109162) in view of Rosenstock et al. (N Engl J Med 2020;383:2107-2116) as applied to claims 10-12, 14-16, 25-30 and 32-34 above, and further in view of Kawai et al. (Proc Natl Acad Sci USA. 2020 Nov 11; 117(47): 29959-29967).
This rejection applies to the elected insulinotropic GLP-1 compound.
The teachings of Norrman and Rosenstock et al. have been discussed above.
Norrman and Rosenstock et al. do not teach the elected insulinotropic GLP-1 compound.
Kawai et al. teach LY3502970 (which corresponds to the elected insulinotropic GLP-1 compound) for the treatment of type 2 diabetes (abstract; passim).
The MPEP 2144.06 states that it is obvious to substitute equivalents known for the same purpose.
In the instant case, it would have been obvious to substitute the insulinotropic GLP-1 compound of Norrman for the insulinotropic GLP-1 compound of Kawai et al.
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 10-12, 14-16, 25-30 and 32-34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 and 17-22 of copending Application No. 18/730552 (or over claims 15-25, 27-29, 37-38, 46 and 56-81 of copending Application No. 17/758089; or over claims 66-74 of copending Application No. 17/758108) in view of Kawai et al. (Proc Natl Acad Sci USA. 2020 Nov 11; 117(47): 29959-29967).
For the sake of brevity, the rejections of ‘552, ‘089 and ‘108 will be addressed together.
‘552, ‘089 and ‘108 teach overlapping acylated insulin species for the treatment of diabetes.
‘552, ‘089 and ‘108 do not teach the claimed insulinotropic GLP-1 compound.
Kawai et al. teach LY3502970 (which corresponds to the elected insulinotropic GLP-1 compound) for the treatment of type 2 diabetes (abstract; passim).
The MPEP 2144.06 states that "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from them having been individually taught in the prior art." In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960). As the court explained in Crockett, the idea of combining them flows logically from them having been individually taught in prior art.
Therefore, since the references teach that acylated insulins and LY3502970 are effective in treating diabetes, it would have been obvious to combine the two compounds with the expectation that such a combination would be effective in treating diabetes. Thus, combining them flows logically from them having been individually taught in prior art.
With respect to the claimed amounts and ratios of acylated insulin and LY3502970, the MPEP 2144.05 A states that “[G]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)”.
Since Applicant has not disclosed that the specific limitations recited in the instant claims are for any particular purpose or solve any stated problem, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum amounts and ratios of acylated insulin and LY3502970 by normal optimization procedures known in the pharmaceutical art.
This is a provisional nonstatutory double patenting rejection.
Claims 10-12, 14-16, 25-30 and 32-34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 26-30, 33-34, 37-38 and 42-43 of copending Application No. 17/758113 (or over claims 1-21 and 25 of copending Application No. 18/571417; or over claims 1-18, 21-27 and 32 of copending Application No. 18/572989) in view of Rosenstock et al. (N Engl J Med 2020;383:2107-2116).
For the sake of brevity, the rejections of ‘113, ‘417 and ‘989 will be addressed together.
‘113, ‘417 and ‘989 teach overlapping insulinotropic GLP-1 compounds species for the treatment of diabetes.
‘113, ‘417 and ‘989 do not teach the elected insulin derivative (i.e. Insulin icodec).
Rosenstock et al. teach Insulin icodec for the treatment of type 2 diabetes (abstract; passim).
The MPEP 2144.06 states that "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from them having been individually taught in the prior art." In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960). As the court explained in Crockett, the idea of combining them flows logically from them having been individually taught in prior art.
Therefore, since the references teach that Insulin icodec and insulinotropic GLP-1 compounds are effective in treating diabetes, it would have been obvious to combine the two compounds with the expectation that such a combination would be effective in treating diabetes. Thus, combining them flows logically from them having been individually taught in prior art.
With respect to the claimed amounts and ratios of Insulin icodec and insulinotropic GLP-1 compounds, the MPEP 2144.05 A states that “[G]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)”.
Since Applicant has not disclosed that the specific limitations recited in the instant claims are for any particular purpose or solve any stated problem, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum amounts and ratios of Insulin icodec and insulinotropic GLP-1 compounds by normal optimization procedures known in the pharmaceutical art.
This is a provisional nonstatutory double patenting rejection.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SERGIO COFFA whose telephone number is (571)270-3022. The examiner can normally be reached M-F: 6AM-4PM.
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/SERGIO COFFA Ph.D./
Primary Examiner
Art Unit 1658
/SERGIO COFFA/Primary Examiner, Art Unit 1658
Prosecution Insights