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
Claim Status
Claims 1, 5-8, 11, 13 and 15-19 are pending. Claims 9-10, 12 and 14 have been canceled. Claims 1, 5-8, 11, 13, 15-16 and 19 have been amended. Claims 1, 5-8, 11, 13 and 15-19 are presently under consideration.
Claim Rejections - 35 USC § 112
The rejection of claims 1 and 5-19 under 35 USC 112(b) is withdrawn in view of the amendments to the claims.
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.
This rejection has been modified.
Claims 1, 5-8, 11 and 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Due Larsen et al. (WO 2018/104561).
With respect to claims 1, 5-8 and 16, Due Larsen et al. teach a method of reducing or inhibiting weight gain, reducing gastric emptying or intestinal transit, reducing food intake, reducing appetite, or promoting weight loss in a subject in need thereof, the method comprising administering a GLP-1/GLP-2 dual agonist represented by the formula: R1-X*-U-R2 (claims 1 and 54), wherein R1 is Hy and/or R2 is OH (claim 39), and wherein X* or X*-U has the sequence H[Aib]EGSFTSELATILD[K([17-carboxy-heptadecanoyl]-isoGlu)]QAARDFIAWLIQHKITD (claim 42, 1st compound on page 91), wherein the patient is a human (page 21, lines 30-33; page 59, lines 1 and 18; passim).
The GLP-1/GLP-2 dual agonist of Due Larsen et al. corresponds to instantly claimed compound 18.
Due Larsen et al. also teach that the dual agonist is for use in a method of prophylaxis or treatment of obesity, morbid obesity, obesity-linked gallbladder disease, obesity-induced sleep apnea, inadequate glucose control, glucose tolerance, dyslipidaemia, diabetes, pre-diabetes, metabolic syndrome or hypertension (claim 51).
Due Larsen et al. do not specifically teach the claimed dose (i.e. about 1.5 mg to about 10.0 mg).
However, Due Larsen et al. teach that “[a]dministration of a compound or pharmaceutical composition of the present invention is commenced at lower dosage levels, with dosage levels being increased until the desired effect of preventing/treating the relevant medical indication is achieved. This would define a therapeutically effective amount” (page 58, lines 33-37).
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 dosage and dosing regimen of the GLP-1/GLP-2 dual agonist of Due Larsen et al. by normal optimization procedures known in the pharmaceutical art.
With respect to claim 11, Due Larsen et al. teach administering the GLP-1/GLP-2 dual agonist by injection (page 18, lines 1-3), and exemplifies subcutaneous injection (page 79, lines 12-14).
With respect to claims 15 and 17, Due Larsen et al. teach that the composition is a pharmaceutical composition and the carrier is a pharmaceutically acceptable carrier (claim 45).
Response to Arguments
Applicant’s arguments filed on 9/2/2026 have been fully considered but they are not persuasive.
Applicant argues that “[L]arsen discloses Compound 18 among 68 alternative GLP-1 /GLP-2 dual agonists. However, there is not a suggestion that Compound 18 would be an effective choice for treatment of obesity in human patients at the dose levels and interval claimed. The Examples of Larsen test receptor potency against GLP-1 and GLP-2, and these studies reveal that Compound 18 is not the best performer for either receptor (Table 2 of Larsen). Table 3 of Larsen describes solubility studies in which comparable solubility between Compound 18 and many other peptides was observed across several buffer systems. Many of the peptides were also stable over 14 days at 40 °C as shown by Example 4 of Larsen. Larsen also does not mention any appropriate dose amounts or dosing schedules for human patients and does not provide any pharmacodynamic studies that could inform the skilled person to make any such selections. Accordingly, Larsen provides no motivation to select Compound 18 for further study in the development of a dosing regimen suitable for human use, and no expectation that Compound 18 would be an appropriate selection in the treatment of human patients on a once weekly dosing schedule at between 1.5 mg and 10.0 mg in the claimed methods. The present specification describes the determination of the Compound 18 plasma half-life in human patients. Example 3 (page 96, lines 27-29) describes how the pharmacodynamic results for Compound 18 enable a once-weekly dosing schedule. Once weekly dosing was further shown to preserve appetite suppression effects via mixed meal test analyses (pages 91-92, Tables 11 and 12). Importantly, these effects were observed over several weeks. Nothing in Larsen renders predictable to the skilled person the effects of administering Compound 18 at the dose amount and frequency for treating obesity in human patients, as claimed”.
Applicant’s arguments are not persuasive because Due Larsen et al. teach that the GLP-1 /GLP-2 dual agonist Compound 18 is used to treat obesity, morbid obesity, obesity-linked gallbladder disease, and obesity-induced sleep apnea (claim 51), and further teach that “[a]dministration of a compound or pharmaceutical composition of the present invention is commenced at lower dosage levels, with dosage levels being increased until the desired effect of preventing/treating the relevant medical indication is achieved. This would define a therapeutically effective amount” (page 58, lines 33-37).
Furthermore, the MPEP 2123 states that “[D]isclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994) (The invention was directed to an epoxy impregnated fiber-reinforced printed circuit material. The applied prior art reference taught a printed circuit material similar to that of the claims but impregnated with polyester-imide resin instead of epoxy. The reference, however, disclosed that epoxy was known for this use, but that epoxy impregnated circuit boards have "relatively acceptable dimensional stability" and "some degree of flexibility," but are inferior to circuit boards impregnated with polyester-imide resins. The court upheld the rejection concluding that applicant’s argument that the reference teaches away from using epoxy was insufficient to overcome the rejection since "Gurley asserted no discovery beyond what was known in the art." Id. at 554, 31 USPQ2d at 1132.).
Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
Therefore, since Due Larsen et al. does not criticize, discredit, or otherwise discourage the use of Compound 18, one of ordinary skills in the art would have been motivated to discover the optimum dosage and dosing regimen of said compound.
The skilled artisan would have had a reasonable expectation of success because Due Larsen et al. teach that the dual agonists of the invention (which include Compound 18) are used to treat obesity, morbid obesity, obesity-linked gallbladder disease, and obesity-induced sleep apnea.
For the reasons stated above the rejection is maintained.
This rejection is maintained.
Claims 1, 5-8, 11, 13 and 15-17are rejected under 35 U.S.C. 103 as being unpatentable over Due Larsen et al. (WO 2018/104561) as applied to claims 1, 5-8, 11 and 15-17 above, and further in view of Zealand Pharma (R&D Day – Delivering on our commitment to patients; March 2021; cited in the IDS).
The teachings of Due Larsen et al. with respect to claims 1, 5-8, 11 and 15-17 have been discussed above.
Due Larsen et al. do not teach that the patient does not experience side-effects of nausea and/or vomiting following administration of the GLP-1/GLP-2 dual agonist.
Zealand Pharma teaches that the most common adverse events of dapiglutide (i.e. the GLP-1/GLP-2 dual agonist of Due Larsen et al.) were nausea, vomiting and decreased appetite, and further teach that dapiglutide was well-tolerated in single doses up to 7.5 mg (page 45). Similarly, the instant specification demonstrate that all subjects administered 0.07, 0.6 and 1.5 mg did not experience nausea and all subjects administered 0.02, 0.07, 0.2, 0.6 and 1.5 mg did not experience vomiting (Table 5).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to administer a dose lower than 7.5 mg because Zealand Pharma teaches that dapiglutide was well-tolerated in single doses up to 7.5 mg.
Response to Arguments
Applicant’s arguments filed on 9/2/2026 have been fully considered but they are not persuasive.
Applicant arguments with respect to Due Larsen et al. have been addressed above.
Applicant argues that “[Z]ealand Pharma, simultaneously, describes how patients experienced statistically significant increases in small intestine surface area in response to treatment, and these data were collected for treating SBS. Importantly, reduction of appetite is described to be an adverse event in patients with underlying SBS-Zealand Pharma reiterates this separation of intended uses on the pipeline described therein (Zealand Pharma, page 12), where dapiglutide is not grouped with alternative peptide compounds for metabolic disorders (e.g., treatment of obesity). Thus, contrary to the Office's assertions, the description in the cited references that Compound 18 improves performance of the small intestine and resulting nutrient absorption instead suggests that administering Compound 18 would promote weight gain rather than treating obesity as claimed. In view of the prolific relation of Compound 18 to treatment of SBS and increases in intestinal weight described in Larsen and Zealand Pharma, Applicant submits that the cited references do not provide a motivation to pursue, nor a reasonable expectation of success for, the claimed method for treating obesity, morbid obesity, obesity-linked gallbladder disease, or obesity-induced sleep apnea in human patients”.
Applicant’s arguments are not persuasive.
It has been held that the determination that a reference is from a nonanalogous art is twofold. First, we decide if the reference is within the field of the inventor's endeavor. If it is not, we proceed to determine whether the reference is reasonably pertinent to the particular problem with which the inventor was involved. In re Wood, 202 USPQ 171, 174.
In the instant case, Zealand Pharma teaches that the most common adverse events of dapiglutide (i.e. the GLP-1/GLP-2 dual agonist of Due Larsen et al.) were nausea, vomiting and decreased appetite, and further teach that dapiglutide was well-tolerated in single doses up to 7.5 mg.
Furthermore, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham, including the exemplary rationales: (A) Combining prior art elements according to known methods to yield predictable results;
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(B) Simple substitution of one known element for another to obtain predictable results;
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(C) Use of known technique to improve similar devices (methods, or products) in the same way;
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(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
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(E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
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(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
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(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention (MPEP 2143).
The presently claimed invention would be obvious to one of ordinary skill in the art because Zealand Pharma teaches that one of the GLP-1/GLP-2 dual agonist of Due Larsen et al. (i.e. dapiglutide) was well-tolerated in single doses up to 7.5 mg.
For the reasons stated above the rejection is maintained.
This rejection is maintained.
Claims 1, 5-8, 11 and 15-19 are rejected under 35 U.S.C. 103 as being unpatentable over Due Larsen et al. (WO 2018/104561) as applied to claims 1, 5-8, 11 and 15-17 above, and further in view of Lau et al. (US 8129343).
The teachings of Due Larsen et al. with respect to claims 1, 5-8, 11 and 15-17 have been discussed above.
Due Larsen et al. do not teach the claimed isotonic parenteral composition.
Lau et al. teach pharmaceutical compositions for parenteral composition comprising acylated GLP-1 agonists (claims; column 39, lines 53-55; passim).
Lau et al. also teach that “[T]he term "pharmaceutical composition" as used herein means a product comprising an active compound or a salt thereof together with pharmaceutical excipients such as buffer, preservative, and optionally a tonicity modifier and/or a stabilizer” (column 4, lines 57-61).
Lau et al. further teach that the use of an isotonic agent in pharmaceutical compositions is well-known to the skilled person (column 44, lines 9-11), and further teach that the isotonic agent is mannitol (page 43, lines 56-58).
Lau et al. additionally teach that the buffer is selected from the group consisting of sodium acetate, sodium carbonate, citrate, glycylglycine, histidine, glycine, lysine, arginine, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, and tris(hydroxymethyl)-aminomethan, bicine, tricine, malic acid, succinate, maleic acid, fumaric acid, tartaric acid, aspartic acid or mixtures thereof (column 43, lines 5-11).
Lau et al. also teach that the pharmaceutical formulation comprises water (i.e. a solvent) (para bridging columns 41-42).
Lau et al. further teach that the pH of the formulation is from about 6.0 to about 7.5 (para bridging columns 42-43).
One of ordinary skill in the art would have been motivated to make an isotonic parenteral composition having a pH of about 6.0 to about 7.5 comprising: 1) the GLP-1/GLP-2 dual agonist of Due Larsen et al.; 2) a phosphate buffer; 3) mannitol; and 4) water, because Lau et al. teach that the use of 2)-4) in pharmaceutical compositions is well-known to the skilled person.
The skilled artisan would have had a reasonable expectation of success because the pharmaceutical compositions of Lau et al. comprise acylated GLP-1 agonists and are used to treat the same disease instantly claimed (e.g. obesity); and the pharmaceutical compositions of Due Larsen et al. comprise an acetylated dual GLP-1/GLP-2 agonist (i.e. dapiglutide).
With respect to the claimed amounts of phosphate buffer, mannitol and water, 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 of phosphate buffer, mannitol and water by normal optimization procedures known in the pharmaceutical art.
Response to Arguments
Applicant’s arguments filed on 9/2/2026 have been fully considered but they are not persuasive.
Applicant arguments with respect to Due Larsen et al. have been addressed above.
Applicant argues that “[L]au does not suggest comparable compounds would be useful for treating obesity, morbid obesity, obesity-linked gallbladder disease, or obesity-induced sleep apnea. Consequently, the skilled person would not have had any reasonable expectation of success for the claimed method, which uses a different class of compounds than in Lau”.
Applicant’s arguments are not persuasive because Lau et al. teach pharmaceutical compositions for parenteral composition comprising acylated GLP-1 agonists, which clearly constitute analogous art.
One of ordinary skills in the art would have been motivated, with a reasonable expectation of success because the pharmaceutical compositions of Lau et al. comprise acylated GLP-1 agonists and are used to treat the same disease instantly claimed (i.e obesity); and the pharmaceutical compositions of Due Larsen et al. comprise an acetylated dual GLP-1/GLP-2 agonist (i.e. dapiglutide).
For the reasons stated above the rejection is maintained.
Conclusion
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.
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
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