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 .
Claim Status
Claims 1-38, and 44-46 are cancelled. Claim 68 is new. Claims 39-43 and 47-68 are new, pending and under examination.
Priority
This application filed on PCT/EP2022/063746 filed on 5/20/2022, which claims priority to European applications EP22154200.4 filed on 1/31/2022 and EP21175174.8 filed on 5/21/2021.
Objections/Rejections Withdrawn
The objections to claims 39, 41, 52, 58 and 60 are withdrawn per applicant’s amendments to correct the objection.
The objection to claims 40 and 45 are withdrawn per applicant’s deletion of the recitation of energy/fatigue and cancellation of claim 45.
The objection to claims 64 and 65 is withdrawn as applicant provides a preference to keep the language. As options “ part G2A or part G2” and “part G2B or part G2” are provided before “whichever is present”, it is referring to whichever of those options is present.
The rejection under USC 112(b) for claim 41’s recitation of “RAND” is withdrawn per applicant’s amendment to remove this recitation.
The rejection under USC 112(b) for claims 42-44 for indefiniteness of “mean overall health transition score” is withdrawn per applicant’s amendments to remove these recitations.
The rejection under USC 112(b) for claim 47 for indefiniteness of “relative improvement of quality of life is greater than any relative weight loss achieved by the subject…” is withdrawn per applicant’s amendments to remove these recitations.
The rejection under USC 112(b) over claim 58 (and claims 59-66) is withdrawn per applicant’s argument. “release….rapidly” as used in context of the claim is read as being to immediate release of the acarbose and orlistat in the duodenum and jejunum.
The rejection under USC 102 over Alderborn is withdrawn per applicant’s amendments and arguments. There would need to be additional teaching of dose timing that would anticipate the effects of reducing central adiposity and/or reducing fat in the liver.
The rejection under USC 103 over Alderborn, Holmback, and Kolotkin is withdrawn per applicant’s amendments that deleted limitations toward questionnaires. Thus, Kolotkin is no longer needed to teach such limitations deleted from the claims.
As these rejections are withdrawn, applicant’s arguments toward these rejections are now moot.
Claim Rejections – 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 39-41, 47-49, 51, and 54-68 are rejected under 35 U.S.C. 103 as being unpatentable over Alderborn US 20170360715 as evidenced by Payne et al (The Journal of Nutrition, health and aging, 2018, volume 22, pages 1259-1265).
Alderborn teaches “The present invention provides a pharmaceutical or cosmetic modified-release (MR) composition for oral use for the treatment of obesity, overweight and/or obesity” (paragraph 27). Alderborn teaches reducing body weight by administering the composition (paragraphs 332 and claim 65 of Alderborn). Alderborn teaches “a modified-release composition comprising orlistat and acarbose, comprising individually distinct parts with different release patterns: a) a first part, G1, comprising from about 5 to about 70% w/w of the total dose of acarbose, b) a second part, G2A, comprising from about 30 to about 95% w/w of the total dose of acarbose, c) a third part, G2B, comprising from about 10 to about 90% w/w of the total dose of orlistat, and d) a fourth part, G3, comprising from about 10 to about 80% w/w of the total dose of orlistat, and the total concentration of acarbose and orlistat, respectively, in the composition is 100% w/w.” (abstract). Alderborn teaches “A modified-release composition according to claim 35, wherein (a) G1 is a DRDC-PRGASTRIC part that releases acarbose in a prolonged manner, (b) G2 is a DREC-RRPROX SI part that releases acarbose and orlistat in the proximal small intestine, and (c) G3 is a DRDC-PRGASTRIC and/or DREC-PRINTESTINAL part that releases orlistat in the proximal part of the small intestine until the end of jejunum.” (claim 36 of Alderborn). Alderborn teaches polysorbate 80 as a non-ionic surfactant for the composition (claim 49 of Alderborn). Alderborn teaches treating conditions like overweight, obesity, type 2 diabetes, impaired glucose tolerance, NAFLD, and metabolic syndrome by administering the composition with the orlistat and acarbose (claims 57 and 60 of Alderborn). Example 1A and example 1B provides for 90mg orlistat and 30mg of acarbose in a multi-unit tablet. This is a 3:1 ratio of orlistat to acarbose. Example 1 (1A and 1B) provides for the multiple unit tablet with granules having acarbose or orlistat with granules having delay coatings or enteric coatings. Example 1E teaches 60 mg orlistat and 20 mg acarbose (also examples 1F and 1H). Alderborn teaches granules with 3.1% orlistat and 27% of hypromellose (HPMC) (example 1C and 1O). In example 1O, there are granules with 3.8% microcrystalline cellulose, 3.1% acarbose, and 8.1% orlistat. Example 1F has granules with 7.2% orlistat, 1.4% acarbose, and 18.2% microcrystalline cellulose, Eudragit L 100-55, Opadry HPMC, and 0.9% polysorbate 80 in G2 granules. Example 1G has 8.1% orlistat, 1.5% acarbose, 20.4% microcrystalline cellulose, Eudragit L 100-55, and 1% polysorbate 80 in G2 granules. Spheronized G1 granules with HPMC are taught in paragraph 390. Coated G1 granules with microcrystalline cellulose and coated with HPMC are taught in paragraph 389. Enteric coated G2 granules with spheronized pellet cores are taught in paragraph 391. G3 granules are taught in paragraph 392. Hydroxypropylmethylcellulose is present in G1 at a concentration of about 10% to about 50% w/w (paragraph 158). Example 4R provides for 39.7% w/w of microcrystalline cellulose in the total granules. Alderborn teaches micronization of orlistat (paragraph 296). Alderborn teaches orlistat nanoparticles of average size of less than 1 micron (paragraphs 297-299). Alderborn teaches administering on the day (paragraph 464). Alderborn teaches taking the oral dosage form with a meal (paragraphs 307 and 341). Alderborn additionally teaches treatment of nonalcoholic fatty liver disease or nonalcoholic steatohepatitis, and thus, as the drug combination of Alderborn are the same as applicant’s claim, Alderborn would have been reducing fat in the liver in such subjects.
Additionally, in regards to improving quality of life, Alderborn provides for administering modified release granule forms of orlistat and acarbose to subjects to treat overweight and obesity. The improvement in these kind of conditions will increase a subjects quality of life in terms of physical functioning, bodily pains, role limitations, personal or emotional problems, emotional well-being, social functioning, energy, fatigue and general health perception/general health. Alderborn also teaches “The main idea regarding an oral modified-release (MR) pharmaceutical composition of the invention is to reduce pH-dependent degradation of both APIs, slow down GI transit time, increase satiety and reduce weight” (paragraph 133). Thus, a goal of Alderborn is to reduce a subject’s weight if obese or overweight, which would be able to improve health, physical, mental and social functions of the subject. Payne evidences that weight loss intervention increases quality of life and mental health in obese older adults (abstract). Payne provides that “in this study of obese older adults with impaired physical function, a weight loss intervention led to improvements in QOL and mental health. In addition, mood, sleep and QOL measures predicted weight loss and improvements in physical function. These results indicate the importance of evaluating mental health and QOL as part of a weight loss intervention for older adults” (end of discussion). Since Alderborn represents a weight reduction intervention for obese patients with a formulation of orlistat and acarbose as in applicant’s claims, it will lead to improved QOL and mental health measures.
Alderborn teaches the claims as discussed above including concentrations of acarbose and orlistat based on the totals of the composition as noted above.
Alderborn teaches surfactant to prevent agglomerates or clusters and includes polysorbates like polysorbate 80 (paragraph 300). Alderborn teaches 0.5 to 30% w/w of surfactant in G2 and includes polysorbate 80 (paragraphs 160-161). Alderborn teaches hydroxypropylmethylcellulose as a supplement to hydrophobic polymer and provides for concentrations of 10% to 50% w/w (paragraphs 157-158). Alderborn teaches that G2 is designed for delayed release but then it becomes relatively rapid (paragraph 159). Alderborn teaches G1 is designed for prolonged release (paragraph 155). Alderborn teaches coatings and enteric polymers as coating agent for G2 (paragraphs 163-166) with about 15% to 50% w/w enteric polymer (paragraph 166). Alderborn teaches G3 with a water swellable polymer with no mention of a core particle (paragraphs 168-169). Alderborn provides for G2A and G2B portions (paragraph 170). Alderborn provides more information about granule or pellet structure in paragraphs 171-175). Alderborn provides “the data analysis of the observed in vitro and simulations of GI processing of the formulation and each of the two API concentration-time profiles (acarbose and orlistat) in the different GI compartments are shown in FIGS. 4 and 5” (paragraph 182), and thus, uses simulations to determine GI processing of the drugs. Alderborn provides for the 3 types of pellets (paragraphs 195-201). Alderborn teaches for G1 and G3 for prolonged release of orlistat and/or acarbose optionally with up to 40 minutes delay (paragraph 203). Alderborn teaches G2 being enteric coated but designed for rapid release of the drugs in the small intestine (paragraph 203). Alderborn teaches orlistat and acarbose (114-129). Alderborn teaches “i) release a part of the total dose of acarbose in the stomach, but in a delayed manner in order to ensure that particles with acarbose will be well mixed with the food components and chyme in the postprandial stomach, ii) release a part of the total dose of acarbose and a part of the total dose of orlistat in duodenum and jejunum; this release should be relatively fast, as both acarbose and orlistat should be available to exert their effect in duodenum and jejunum, and iii) release of a part of the total dose of orlistat in duodenum and jejunum.” (paragraphs 31-34). Alderborn teaches microcrystalline cellulose or sugar alcohol based spheres are used as cores (paragraph 389). These would be inert cores as they don’t have drug. G1 and G2 are noted as having cores while G3 does not (paragraphs 389-392). Paragraphs 31-38 provides for duodenum and jejunum.
Alderborn does not directly provide that the treatment with dosing regimen that would reduce central adiposity or fat in the liver, however, it teaches orlistat and acarbose, amounts of applicant’s claims, dosage forms of applicant’s claims and treating subjects with obesity and overweightness. Alderborn’s teachings also provide the option of treating such individuals with fatty liver diseases.
One of ordinary skill in the art before the time of filing would have worked within the overlapping concentrations of orlistat and acarbose for each portion (G1, G2A, G2B and G3) based on total composition concentration from Alderborn to provide for total concentrations and concentrations based on part for each of the drugs with a reasonable expectation of success in making the formulation that would provide for modified release of these drugs when administered (MPEP 2144.05). One of ordinary skill in the art before the time of filing would also have adjusted the amounts of structural components such as coatings and enteric and other polymers to provide for compositions with the proper release of each drug based on Alderborn’s teachings of overlapping concentrations and the desired to adjust release of each drug from each portion of the formulation. Thus, one would have a reasonable expectation of success in providing the formulations of the claims by teachings of Alderborn with the ability to provide for modified release of the drugs to provide some release in the stomach and other release in the small intestine (duodenum and jejunum are parts of the small intestine). This would allow for a treatment that would be administered to patients to treat conditions such as obesity, overweightness and type II diabetes to improve the lives of those subjects by managing weight and treating disease.
Claims 42-43, 50, and 52-53 in addition to claims 39-41, 47-49, 51, and 54-68 are rejected under 35 U.S.C. 103 as being unpatentable over Alderborn US 20170360715 and Holmback et al (Obesity Science and Practice, Feb 2020, volume 6, pages 313-323) as evidenced by Payne et al (The Journal of Nutrition, health and aging, 2018, volume 22, pages 1259-1265).
Alderborn teaches the claims as discussed above. Alderborn teaches in regards to acarbose, “By inhibiting the luminal digestion and subsequent absorption of carbohydrates, the concentrations of glucose in blood sugar increases slower postprandially, and the patient's insulin need is reduced” (paragraph 129). Alderborn teaches that orlistat acts by preventing intestinal absorption of dietary fats through inhibition of luminal digestion (paragraph 118).
Alderborn does not teach a timing of the administration. Alderborn does not teach reducing body fat percentage or sagittal abdominal diameter (requires administering the drugs for longer time frames).
Holmback teaches administering combinations of orlistat and acarbose for treating people with obesity (abstract). Holmback teaches a modified release dosage form was used (abstract). Holmback teaches 90/30 and 120/40 combinations of orlistat and acarbose (abstract and table 1). Holmback teaches 2 weeks of daily treatment for its study (section 2.1). Holmback teaches 3 times a day (section 2.1). In section 5, it is indicated that results need confirmation in a study of longer duration with a more diverse population where weight loss is the primary outcome. Table 1 of Holmback teaches decrease of BMI and body fat with combination treatments vs conventional orlistat. Holmback teaches minor reductions in body weight during the 14 day study (page 319 and table 1 with BMI).
Therefore, one of ordinary skill in the art before the time of filing would have used durations of 2 weeks or more in treating patients with a modified release form of orlistat and acarbose in claimed amounts by the combined teachings of Alderborn and Holmback with Alderborn teaching treatment of subjects with obesity and overweightness with orlistat/acarbose combinations that are taught in its disclosure. Holmback recognizes the dose of 120 mg orlistat and 40 mg acarbose. The doses of orlistat and acarbose would be adjusted and optimized for treatment of the overweight or obese subjects based on teachings of Alderborn, which recognizes the effects that these drugs have in the formulation. Holmback recognizes the dose of 120 mg orlistat and 40 mg acarbose. Although Holmback teaches using 2 weeks for its studies, it recognizes using longer times of treatment to observe the effects on weight loss. Holmback also recognizes administering three times per day for orlistat/acarbose dosages. In adjusting the dose amounts and dosing of orlistat (drug that lowers absorption of dietary fats) and acarbose (drug that lowers absorption of dietary carbohydrates) based on teachings and methods of the references, one of ordinary skill in the art would achieve claimed treatment of obesity or overweightness in individuals which will lead to the claimed observations of lower body fat percentage and reduced sagittal abdominal diameter. One of ordinary skill in the art would optimize the dosing of the orlistat and acarbose to achieve better treat obesity or overweightness in subjects. There would be a reasonable expectation of success of utilizing modified release forms of these drugs in time durations of the claims to treat obesity or overweightness in subjects by the combination of Alderborn and Holmback, which teach combinations of orlistat and acarbose to treat subjects.
Response to Applicant’s Arguments over the Rejections under USC 103
Applicant argues that only applicant’s examples provide for decreased body fat and decreased waist circumference and decreased sagittal diameter and these are not features taught by Alderborn. It remains that Alderborn provides for treatment of patients with obesity or who are overweight by administering oral compositions having dose amounts of orlistat and acarbose as in applicant’s claims. Alderborn also provides that orlistat reduces absorption of fats while acarbose reduces absorption of carbohydrates in the intestines, which lowers the amounts of fats and carbohydrates absorbed by the body. Thus, Alderborn is providing the same compounds, which would have the same functions/effects in the body, in similar amounts to patients with the condition of obesity or overweightness (subjects that have central adiposity) and by routine adjustments in dosing would achieve nutrient absorption reduction, fat reduction and the waist size reduction that is associated with the treatment as these would be targeted in the treating of obesity and overweightness as provided by Alderborn. Thus, these effects would be achieved by routine optimizations in dosing when treating patients with obesity or overweightness with orlistat/acarbose in similar amounts as in Alderborn’s teachings. Note in MPEP 2112 II “Inherent feature does not need to be recognized at the relevant time”.
Applicant argues that Holmback in combination with Alderborn does not teach the claims as Holmback sees no significant differences in body composition or waist circumference after its 2 week treatment. However, Holmback does recognize in its disclosure the need for extension of the treatment time to examine effects on weight reduction. Additionally, the teachings of Alderborn in this rejection under USC 103 provide for the treatment of obese and overweightness, which provides these conditions will be treated.
For these reasons, these rejections under USC 103 are maintained and are modified accordingly per the amendments to applicant’s claims that specify what the treatment is for, the dose amounts of orlistat and acarbose used and the effectiveness provided.
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 39-43 and 47-68 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 26 and 27 in view of claims 1-24 of U.S. Patent No. 10561617 in view of Alderborn US 20170360715, Holmback et al (Obesity Science and Practice, Feb 2020, volume 6, pages 313-323) and Kolotkin et al (Clinical Obesity, 2019, volume 9, pages 1-11) as evidenced by Payne et al (The Journal of Nutrition, health and aging, 2018, volume 22, pages 1259-1265).
Although the claims at issue are not identical, they are not patentably distinct from each other because ‘617 claims a materially similar formulation for treatment of subjects with obesity.
‘617 claims do not provide for questionnaires other orlistat and acarbose amounts of the claims, micronized form of orlistat and microcrystalline cellulose.
Alderborn teaches surfactant to prevent agglomerates or clusters and includes polysorbates like polysorbate 80 (paragraph 300). Alderborn teaches 0.5 to 30% w/w of surfactant in G2 and includes polysorbate 80 (paragraphs 160-161). Alderborn teaches hydroxypropylmethylcellulose as a supplement to hydrophobic polymer and provides for concentrations of 10% to 50% w/w (paragraphs 157-158). Alderborn teaches that G2 is designed for delayed release but then it becomes relatively rapid (paragraph 159). Alderborn teaches G1 is designed for prolonged release (paragraph 155). Alderborn teaches coatings and enteric polymers as coating agent for G2 (paragraphs 163-166) with about 15% to 50% w/w enteric polymer (paragraph 166). Alderborn teaches G3 with a water swellable polymer with no mention of a core particle (paragraphs 168-169). Alderborn provides for G2A and G2B portions (paragraph 170). Alderborn provides more information about granule or pellet structure in paragraphs 171-175). Alderborn provides “the data analysis of the observed in vitro and simulations of GI processing of the formulation and each of the two API concentration-time profiles (acarbose and orlistat) in the different GI compartments are shown in FIGS. 4 and 5” (paragraph 182), and thus, uses simulations to determine GI processing of the drugs. Alderborn provides for the 3 types of pellets (paragraphs 195-201). Alderborn teaches for G1 and G3 for prolonged release of orlistat and/or acarbose optionally with up to 40 minutes delay (paragraph 203). Alderborn teaches G2 being enteric coated but designed for rapid release of the drugs in the small intestine (paragraph 203). Alderborn teaches orlistat and acarbose (114-129). Alderborn teaches “i) release a part of the total dose of acarbose in the stomach, but in a delayed manner in order to ensure that particles with acarbose will be well mixed with the food components and chyme in the postprandial stomach, ii) release a part of the total dose of acarbose and a part of the total dose of orlistat in duodenum and jejunum; this release should be relatively fast, as both acarbose and orlistat should be available to exert their effect in duodenum and jejunum, and iii) release of a part of the total dose of orlistat in duodenum and jejunum.” (paragraphs 31-34). Alderborn teaches microcrystalline cellulose or sugar alcohol based spheres are used as cores (paragraph 389). These would be inert cores as they don’t have drug. G1 and G2 are noted as having cores while G3 does not (paragraphs 389-392). Paragraphs 31-38 provides for duodenum and jejunum.
Holmback teaches administering combinations of orlistat and acarbose for treating people with obesity (abstract). Holmback teaches a modified release dosage form was used (abstract). Holmback teaches 90/30 and 120/40 combinations of orlistat and acarbose (abstract and table 1). Holmback teaches 2 weeks of daily treatment for its study (section 2.1). In section 5, it is indicated that results need confirmation in a study of longer duration. Holmback does administer a questionnaire for body/physical functions related to gastric symptoms (table 2 and section 2.6).
Kolotkin teaches the IWQOL-Lite (version of IWQOL) as a widely used evaluation in weight loss interventions (abstract). Kolotkin provides that this questionnaire is reliable, valid and responsive measure of weight related functioning in populations commonly targeted for obesity clinical trials (section 5).
One of ordinary skill in the art before the time of filing would have worked within the overlapping concentrations of orlistat and acarbose for each portion (G1, G2A, G2B and G3) based on total composition concentration from Alderborn to provide for total concentrations and concentrations based on part for each of the drugs with a reasonable expectation of success in making the formulation that would provide for modified release of these drugs when administered (MPEP 2144.05) when considering claims of ‘617. One of ordinary skill in the art before the time of filing would also have adjusted the amounts of structural components such as coatings and enteric and other polymers to provide for compositions with the proper release of each drug based on Alderborn’s teachings of overlapping concentrations and the desired to adjust release of each drug from each portion of the formulation. Thus, one would have a reasonable expectation of success in providing the formulations of the claims by teachings of Alderborn with the ability to provide for modified release of the drugs to provide some release in the stomach and other release in the small intestine (duodenum and jejunum are parts of the small intestine). This would allow for a treatment that would be administered to patients to treat conditions such as obesity and type II diabetes to improve the lives of those subjects by managing weight and treating disease. Therefore, one of ordinary skill in the art before the time of filing would have used durations of 2 weeks or more in treating patients with a modified release form of orlistat and acarbose by the combined teachings of Alderborn and Holmback. Holmback also obviates the use of questionnaires to follow physical functions of the subjects. There would be a reasonable expectation of success of utilizing modified release forms of these drugs in time durations of the claims to get results. One of ordinary skill in the art before the time of filing would have routinely used questionnaires such as IWQOL to collect patient data including from subjects undergoing treatment for obesity (obesity clinical trials). As Alderborn provides for the treatment formulation of applicant’s claims (modified release form of orlistat and acarbose including 90/30 and 120/40 and administering it to subjects with obesity for treatment, similar results would be obtained via the routine questionnaires. Thus, there is a reasonable expectation of success in administering questionnaires like IWQOL to subjects receiving such treatments for obesity and obtaining similar results from those treatments.
Claims 39-43 and 47-68 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14 and 15 in view of claims 1-13 of U.S. Patent No. 11975105 in view of Alderborn US 20170360715, Holmback et al (Obesity Science and Practice, Feb 2020, volume 6, pages 313-323) and Kolotkin et al (Clinical Obesity, 2019, volume 9, pages 1-11) as evidenced by Payne et al (The Journal of Nutrition, health and aging, 2018, volume 22, pages 1259-1265).
Although the claims at issue are not identical, they are not patentably distinct from each other because ‘105 claims a materially similar formulation for treatment of subjects with obesity.
‘105 claims do not provide for questionnaires other orlistat and acarbose amounts of the claims, micronized form of orlistat and microcrystalline cellulose.
Alderborn teaches surfactant to prevent agglomerates or clusters and includes polysorbates like polysorbate 80 (paragraph 300). Alderborn teaches 0.5 to 30% w/w of surfactant in G2 and includes polysorbate 80 (paragraphs 160-161). Alderborn teaches hydroxypropylmethylcellulose as a supplement to hydrophobic polymer and provides for concentrations of 10% to 50% w/w (paragraphs 157-158). Alderborn teaches that G2 is designed for delayed release but then it becomes relatively rapid (paragraph 159). Alderborn teaches G1 is designed for prolonged release (paragraph 155). Alderborn teaches coatings and enteric polymers as coating agent for G2 (paragraphs 163-166) with about 15% to 50% w/w enteric polymer (paragraph 166). Alderborn teaches G3 with a water swellable polymer with no mention of a core particle (paragraphs 168-169). Alderborn provides for G2A and G2B portions (paragraph 170). Alderborn provides more information about granule or pellet structure in paragraphs 171-175). Alderborn provides “the data analysis of the observed in vitro and simulations of GI processing of the formulation and each of the two API concentration-time profiles (acarbose and orlistat) in the different GI compartments are shown in FIGS. 4 and 5” (paragraph 182), and thus, uses simulations to determine GI processing of the drugs. Alderborn provides for the 3 types of pellets (paragraphs 195-201). Alderborn teaches for G1 and G3 for prolonged release of orlistat and/or acarbose optionally with up to 40 minutes delay (paragraph 203). Alderborn teaches G2 being enteric coated but designed for rapid release of the drugs in the small intestine (paragraph 203). Alderborn teaches orlistat and acarbose (114-129). Alderborn teaches “i) release a part of the total dose of acarbose in the stomach, but in a delayed manner in order to ensure that particles with acarbose will be well mixed with the food components and chyme in the postprandial stomach, ii) release a part of the total dose of acarbose and a part of the total dose of orlistat in duodenum and jejunum; this release should be relatively fast, as both acarbose and orlistat should be available to exert their effect in duodenum and jejunum, and iii) release of a part of the total dose of orlistat in duodenum and jejunum.” (paragraphs 31-34). Alderborn teaches microcrystalline cellulose or sugar alcohol based spheres are used as cores (paragraph 389). These would be inert cores as they don’t have drug. G1 and G2 are noted as having cores while G3 does not (paragraphs 389-392). Paragraphs 31-38 provides for duodenum and jejunum.
Holmback teaches administering combinations of orlistat and acarbose for treating people with obesity (abstract). Holmback teaches a modified release dosage form was used (abstract). Holmback teaches 90/30 and 120/40 combinations of orlistat and acarbose (abstract and table 1). Holmback teaches 2 weeks of daily treatment for its study (section 2.1). In section 5, it is indicated that results need confirmation in a study of longer duration. Holmback does administer a questionnaire for body/physical functions related to gastric symptoms (table 2 and section 2.6).
Kolotkin teaches the IWQOL-Lite (version of IWQOL) as a widely used evaluation in weight loss interventions (abstract). Kolotkin provides that this questionnaire is reliable, valid and responsive measure of weight related functioning in populations commonly targeted for obesity clinical trials (section 5).
One of ordinary skill in the art before the time of filing would have worked within the overlapping concentrations of orlistat and acarbose for each portion (G1, G2A, G2B and G3) based on total composition concentration from Alderborn to provide for total concentrations and concentrations based on part for each of the drugs with a reasonable expectation of success in making the formulation that would provide for modified release of these drugs when administered (MPEP 2144.05) when considering claims of ‘105. One of ordinary skill in the art before the time of filing would also have adjusted the amounts of structural components such as coatings and enteric and other polymers to provide for compositions with the proper release of each drug based on Alderborn’s teachings of overlapping concentrations and the desired to adjust release of each drug from each portion of the formulation. Thus, one would have a reasonable expectation of success in providing the formulations of the claims by teachings of Alderborn with the ability to provide for modified release of the drugs to provide some release in the stomach and other release in the small intestine (duodenum and jejunum are parts of the small intestine). This would allow for a treatment that would be administered to patients to treat conditions such as obesity and type II diabetes to improve the lives of those subjects by managing weight and treating disease. Therefore, one of ordinary skill in the art before the time of filing would have used durations of 2 weeks or more in treating patients with a modified release form of orlistat and acarbose by the combined teachings of Alderborn and Holmback. Holmback also obviates the use of questionnaires to follow physical functions of the subjects. There would be a reasonable expectation of success of utilizing modified release forms of these drugs in time durations of the claims to get results. One of ordinary skill in the art before the time of filing would have routinely used questionnaires such as IWQOL to collect patient data including from subjects undergoing treatment for obesity (obesity clinical trials). As Alderborn provides for the treatment formulation of applicant’s claims (modified release form of orlistat and acarbose including 90/30 and 120/40 and administering it to subjects with obesity for treatment, similar results would be obtained via the routine questionnaires. Thus, there is a reasonable expectation of success in administering questionnaires like IWQOL to subjects receiving such treatments for obesity and obtaining similar results from those treatments.
Claims 39-43 and 47-68 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 53 and 54 in view of claims 35-49 of copending Application No. 18/631,545 (reference application) (now US Patent 12629340) in view of Alderborn US 20170360715, Holmback et al (Obesity Science and Practice, Feb 2020, volume 6, pages 313-323) and Kolotkin et al (Clinical Obesity, 2019, volume 9, pages 1-11) as evidenced by Payne et al (The Journal of Nutrition, health and aging, 2018, volume 22, pages 1259-1265).
Although the claims at issue are not identical, they are not patentably distinct from each other because ‘545 claims a materially similar formulation for treatment of subjects with obesity.
‘545 claims do not provide for questionnaires other orlistat and acarbose amounts of the claims, micronized form of orlistat and microcrystalline cellulose.
Alderborn teaches surfactant to prevent agglomerates or clusters and includes polysorbates like polysorbate 80 (paragraph 300). Alderborn teaches 0.5 to 30% w/w of surfactant in G2 and includes polysorbate 80 (paragraphs 160-161). Alderborn teaches hydroxypropylmethylcellulose as a supplement to hydrophobic polymer and provides for concentrations of 10% to 50% w/w (paragraphs 157-158). Alderborn teaches that G2 is designed for delayed release but then it becomes relatively rapid (paragraph 159). Alderborn teaches G1 is designed for prolonged release (paragraph 155). Alderborn teaches coatings and enteric polymers as coating agent for G2 (paragraphs 163-166) with about 15% to 50% w/w enteric polymer (paragraph 166). Alderborn teaches G3 with a water swellable polymer with no mention of a core particle (paragraphs 168-169). Alderborn provides for G2A and G2B portions (paragraph 170). Alderborn provides more information about granule or pellet structure in paragraphs 171-175). Alderborn provides “the data analysis of the observed in vitro and simulations of GI processing of the formulation and each of the two API concentration-time profiles (acarbose and orlistat) in the different GI compartments are shown in FIGS. 4 and 5” (paragraph 182), and thus, uses simulations to determine GI processing of the drugs. Alderborn provides for the 3 types of pellets (paragraphs 195-201). Alderborn teaches for G1 and G3 for prolonged release of orlistat and/or acarbose optionally with up to 40 minutes delay (paragraph 203). Alderborn teaches G2 being enteric coated but designed for rapid release of the drugs in the small intestine (paragraph 203). Alderborn teaches orlistat and acarbose (114-129). Alderborn teaches “i) release a part of the total dose of acarbose in the stomach, but in a delayed manner in order to ensure that particles with acarbose will be well mixed with the food components and chyme in the postprandial stomach, ii) release a part of the total dose of acarbose and a part of the total dose of orlistat in duodenum and jejunum; this release should be relatively fast, as both acarbose and orlistat should be available to exert their effect in duodenum and jejunum, and iii) release of a part of the total dose of orlistat in duodenum and jejunum.” (paragraphs 31-34). Alderborn teaches microcrystalline cellulose or sugar alcohol based spheres are used as cores (paragraph 389). These would be inert cores as they don’t have drug. G1 and G2 are noted as having cores while G3 does not (paragraphs 389-392). Paragraphs 31-38 provides for duodenum and jejunum.
Holmback teaches administering combinations of orlistat and acarbose for treating people with obesity (abstract). Holmback teaches a modified release dosage form was used (abstract). Holmback teaches 90/30 and 120/40 combinations of orlistat and acarbose (abstract and table 1). Holmback teaches 2 weeks of daily treatment for its study (section 2.1). In section 5, it is indicated that results need confirmation in a study of longer duration. Holmback does administer a questionnaire for body/physical functions related to gastric symptoms (table 2 and section 2.6).
Kolotkin teaches the IWQOL-Lite (version of IWQOL) as a widely used evaluation in weight loss interventions (abstract). Kolotkin provides that this questionnaire is reliable, valid and responsive measure of weight related functioning in populations commonly targeted for obesity clinical trials (section 5).
One of ordinary skill in the art before the time of filing would have worked within the overlapping concentrations of orlistat and acarbose for each portion (G1, G2A, G2B and G3) based on total composition concentration from Alderborn to provide for total concentrations and concentrations based on part for each of the drugs with a reasonable expectation of success in making the formulation that would provide for modified release of these drugs when administered (MPEP 2144.05) when considering claims of ‘545. One of ordinary skill in the art before the time of filing would also have adjusted the amounts of structural components such as coatings and enteric and other polymers to provide for compositions with the proper release of each drug based on Alderborn’s teachings of overlapping concentrations and the desired to adjust release of each drug from each portion of the formulation. Thus, one would have a reasonable expectation of success in providing the formulations of the claims by teachings of Alderborn with the ability to provide for modified release of the drugs to provide some release in the stomach and other release in the small intestine (duodenum and jejunum are parts of the small intestine). This would allow for a treatment that would be administered to patients to treat conditions such as obesity and type II diabetes to improve the lives of those subjects by managing weight and treating disease. Therefore, one of ordinary skill in the art before the time of filing would have used durations of 2 weeks or more in treating patients with a modified release form of orlistat and acarbose by the combined teachings of Alderborn and Holmback. Holmback also obviates the use of questionnaires to follow physical functions of the subjects. There would be a reasonable expectation of success of utilizing modified release forms of these drugs in time durations of the claims to get results. One of ordinary skill in the art before the time of filing would have routinely used questionnaires such as IWQOL to collect patient data including from subjects undergoing treatment for obesity (obesity clinical trials). As Alderborn provides for the treatment formulation of applicant’s claims (modified release form of orlistat and acarbose including 90/30 and 120/40 and administering it to subjects with obesity for treatment, similar results would be obtained via the routine questionnaires. Thus, there is a reasonable expectation of success in administering questionnaires like IWQOL to subjects receiving such treatments for obesity and obtaining similar results from those treatments.
Claims 39-43 and 47-68 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32-33, 38-57 of copending Application No. 18/562,765 (reference application) and Kolotkin et al (Clinical Obesity, 2019, volume 9, pages 1-11) as evidenced by as evidenced by Payne et al (The Journal of Nutrition, health and aging, 2018, volume 22, pages 1259-1265). Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set provides for administering to subjects that are overweight or obese a materially same formulation of orlistat and acarbose. Payne evidences that weight loss intervention increases quality of life and mental health in obese older adults (abstract). Payne provides that “in this study of obese older adults with impaired physical function, a weight loss intervention led to improvements in QOL and mental health. In addition, mood, sleep and QOL measures predicted weight loss and improvements in physical function. These results indicate the importance of evaluating mental health and QOL as part of a weight loss intervention for older adults” (end of discussion).
‘765 does not teach the use of questionnaires during administration of its formulation to subjects.
Kolotkin teaches the IWQOL-Lite (version of IWQOL) as a widely used evaluation in weight loss interventions (abstract). Kolotkin provides that this questionnaire is reliable, valid and responsive measure of weight related functioning in populations commonly targeted for obesity clinical trials (section 5).
One of ordinary skill in the art before the time of filing would have routinely used questionnaires such as IWQOL to collect patient data including from subjects undergoing treatment for obesity (obesity clinical trials). As ‘765 provides for the treatment formulation of applicant’s claims (modified release form of orlistat and acarbose including 90/30 and 120/40 and administering it to subjects with obesity for treatment, similar results would be obtained via the routine questionnaires. Thus, there is a reasonable expectation of success in administering questionnaires like IWQOL to subjects receiving such treatments for obesity and obtaining similar results from those treatments.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Applicant’s Arguments over the Rejection under Non-statutory Double Patenting
Applicant argues the rejections be withdrawn per applicant’s amendments, however, the claims still provide for treating conditions in subjects including obesity and overweightness with combinations of orlistat and acarbose. The combination of references provide for dose amounts, dosing regimens and dose forms that obviate these as existing doses, regimens and dose forms for orlistat and acarbose and treatments therewith.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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