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 Rejections 35 USC 103(a)
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 25-29, 37 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Ubukata et al. (Diabetes Research and Clinical Practice 24, 1996, 1-6)
Ubukata teaches that Mixed solutions with various molar ratios of glucagon and insulin (G/I) were subcutaneously infused continuously for five days by use of the osmotic minipump in the normal rats (Abstract). The concentrations of insulin and glucagon solution were set at the high G/I molar ratio, the moderate G/I molar ratio and the low G/I molar ratio (p. 2, Col;. 1). In addition, the moderate G/I molar ratio group was divided into three sub-groups: low glucagon and low insulin, moderate glucagon and moderate insulin, and high glucagon and high insulin. After five days, the rats were decapitated to measure plasma ketones, free fatty acids (FFA), glucose, insulin and glucagon (p. 2, Col. 2, para. 1-2)
The difference between the instant claims and the prior art is that the prior art does not specifically teach that the composition in mg/ml; however, a range of insulin to glucose formulations administered to study their effects on plasma ketone levels. The molar ratios used in these compositions range from .07 to 2.8 molar ratios of insulin to glucose, which is within the claimed ratio range of 1:1 to 6:1 (p. 2, Col. 1). The specification does not teach the specific molecular with used for the mg/ml to molar ratio calculation, and the prior art is administering the composition that is described by molar ratios, not mg/ml. If the molar ratio of the solution is required to be within 1:1 and 6:1 insulin: glucagon, then the concentration in solution would overlap with the claimed mg/ml in solution. For example, a molar ration of 5mg/ml insulin:1mg/ml glucagon would be approximately 3:1, where the MW of insulin is calculated with 5,808 Da and glucagon calculated with MW 3,484 Da.
Additionally, MPEP 2144.05 states: “Generally, 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 Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art.").[AltContent: rect]
As such, the claimed range of mg/ml concentration taught by the prior art renders the instant claims obvious to optimize within the claimed ranges of concentration because the molar ration overlaps. One would be motivated to do so because the method of Ubukata optimizes the insulin to glucose molar ratio, which requires optimizing the concentration in mg/ml. As such, there is a reasonable expectation of success that the range of insulin: glucagon taught by Ubukata in molar ratios will be effective for the same purpose when measured and optimized using mg/ml ratios that fall within Ubukata’s molar ratio to look at the effects of this ratio on plasma ketones.
This meets the limitations of claims 25-29 by rendering the concentration obvious, based on the prior art teachings and motivation to optimize these concentrations. Claims 37 and 38 are met because Ubukata teaches administration via a subcutaneously inserted mini pump for infusion (p. 2, Col. 2)
Claims 1, 25-35, 37 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Ubukata et al. in view of Prestrelski (US2010/0232001).
The teaching of Ubukata have been described supra.
The difference between the prior art and instant claims 30-32 is that Ubukata does not does not disclose wherein at least one non-aqueous solvent is dimethyl sulfoxide (DMSO) or N-methylpyrrolidone (NMP).
Prestrelski teaches stable formulations for parenteral injection of glucagon and insulin, as well as their analogues and methods of using such formulations to treat hypoglycemia (abstract, 0018-0020). This reference also teaches that one non-aqueous solvent is dimethyl sulfoxide DMSO that can be used for the formulation as a stable solvent [0087, 0104-0105].
It would have been obvious to one of ordinary skill in the art at the filing date of the invention to modify the Ubukata composition to provide wherein at least one non-aqueous solvent is dimethyl sulfoxide (DMSO) or N-methylpyrrolidone (NMP), as taught by Prestrelski, in order to provide for reconstituting dried peptide powder in a solvent system that allows for preparation of a concentrated and stabilized peptide formulation [0015, 0035]. As such, there is a reasonable expectation of success that this solvent will be effective with the formulation of Ubukata.
Claims 30-32 are met because Prestrelski renders it obvious to use the non-aqueous solvent is DMSO. This meets the limitations of claim 1 by rendering it obvious to treat hyperglycemia with insulin and glucagon formulations. Claims 34 and 35 are met because Prestrelski teaches insulin and glucagon analogues in the formulation.
The difference between the prior art and claim 33 is that it does not teach wherein between about 10% and about 40% of the solvent is propylene glycol (PG), glycerol, or a combination of PG and glycerol.
Prestrelski discloses wherein between about 10% and about 40% of the solvent is propylene glycol (PG), glycerol, or a combination of PG and glycerol for reconstituting dried peptide powder with aprotic solvent and co-solvent in an amount from 10-50 percent of the solvent, where co-solvent can be propylene glycol, glycerol, and peptide reconstituted using 20 percent water (aqueous solvent) to the aprotic polar solvent [0087, 0105].
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the Ubukata invention to provide wherein between about 10% and about 40% of the solvent is propylene glycol (PG), glycerol, or a combination of PG and glycerol, as taught by Prestrelski, in order to maintain pH range of peptide formulation [0087]. As such, there is a reasonable expectation of success that this solvent can be used with the formulation of Ubukata.
As such, claim 33 is rendered obvious.
Claims 1, 25-29, 34, 36 and 37 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ubukata et al. in view of Jones (Diabetes Obes Metab November 2016; 18: 1053–1054).
The teachings of Ubukata have been described supra.
The difference between the prior art and the instant claims is that the prior art does not teach hepato-preferential insulin.
Jones teaches basal insulin peglispro (BIL) is a novel insulin analogue that binds insulin lispro covalently via a urethane bond to a 20‐kDa polyethylene glycol molecule(abstract). This reference teaches that the BIL analogue has a molecular weight of ~25.8 kDa, which is approximately three times greater than that of native insulin or most insulin analogues (abstract). This reference teaches that that in normal physiology, insulin is secreted by the pancreas into the hepatic portal vein that delivers insulin directly to the liver and thus the liver sees four times the concentration in comparison with other tissues supplied by the systemic peripheral circulation (p. 1053, Col. 1). Jones teaches that larger insulin molecules are more likely to be relatively hepato‐preferential, suggesting this might be a strategy to achieve more physiological insulin replacement via the subcutaneous route by targeting the liver (p. 1053, Col. 1). This reference further teaches that BIL achieved greater glycated hemoglobin (HbA1c) lowering, weight reduction and fewer nocturnal hypoglycemic episodes than comparator insulin analogues (p. 1053, Col. 1).
As such, it would have been obvious to one of ordinary skill in the art at the filing date of the invention to have taken the method of Ubukata and used the BIL hepato-preferential treatment of Jones because Jones teaches that hepato-preferential insulin may be a more effective way to achieve the desired levels of physiological insulin. One would be motivated to use BIL because Jones teaches that it had preferential results to other insulin analogues in treating hypoglycemic episodes. As such, there is a reasonable expectation of success that BIL will be effective in the formulation of Ubukata in a method of treating hyperglycemia and inhibiting hypoglycemia, as taught by Jones.
As such, instant claim 36 is rendered obvious by the combination of Ubukata and Jones.
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 and 25-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 11,357,829. Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 teaches a method of treatment comprising co-administering insulin and glucagon to a subject, wherein the insulin and glucagon are co-administered at an insulin: glucagon molar ratio between about 1:1 and about 6:1, claim 5 teaches that the co-formulation comprises insulin at a concentration between about 3 mg/ml and about 5 mg/ml, and glucagon at a concentration between about 0.1 mg/ml and about 0.8 mg/ml and claim 17 teaches that the insulin and glucagon are co-administered at an insulin: glucagon molar ratio between about 3:1 and about 5:1, which meet the limitations of instant claims 25-29 by teaching the same ratios and concentrations.
Claims 7-10 of ‘829 teach that between about 20% and about 60% of the solvent (v/v) consists of the one or more non-aqueous solvents, wherein at least one non-aqueous solvent is dimethyl sulfoxide (DMSO) or N-methylpyrrolidone (NMP), which meet instant claims 30 and 31. Claims 9-11 of ‘829 teach that the solvent further includes one or more aqueous solvents, wherein no more than about 40% of the solvent (v/v) consists of the one or more aqueous solvents and wherein between about 10% and about 40% of the solvent is propylene glycol (PG), glycerol, or a combination of PG and glycerol, which meet instant claims 30-33.
Instant claim 1 is met because claim 1 of ‘829 teaches the same method of treating hyperglycemia and hypoglycemia. Instant claims 25-33 are met by claims 1-11 of ‘829 because the same concentrations, ratios and solvents are taught by ‘829. Instant claims 34-35 are met by claims 20-21 teach analogues. Instant claims 37 and 38 are met because claims 12-13 teach administration via an infusion pump or subcutaneously. Instant claim 36 is met because claim 14 teaches hepato-preferential insulin.
As such, instant claims 1 and 25-38 are rejected by the claims of ‘829.
Conclusion
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654
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