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
Response to Amendment
Status of the Claims
Receipt of Applicant’s response, filed 11 Aug 2025 has been entered.
The claims under consideration were submitted 27 Jun 2024.
Claims 1-4 and 6-14 remain pending in the application.
Claim 5 is cancelled.
Claims 1-4 and 6-14 are under consideration.
Rejections Maintained
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1-4 and 6-14 are rejected under 35 U.S.C. 103 as being unpatentable over Chithamabara et al. (US 2010/0086596, published 08 April 2010) in view of Huang et al. (Nutrition 29 (2013) 1259–1265), Weiss et al. (J Vasc Interv Radiol. 2015 May; 26(5): 613–624) and Kassab et al. (Journal of Advances in Chemistry, Vol. 12, No. 3, published 29 January 2016).
Chithambara teaches polymer delivery of active agents, in particular, delivery of octreotide from polymer microspheres without an initial time lag ([0001]). Chithambara teaches that the compositions can be used to treat a disease, disorder or condition in a human patient and that the composition can be administered by any suitable route ([0033]). Chithambara teaches that octreotide can be used in patients who have an inadequate response to surgery or for whom surgical resection is not an option and teaches that octreotide is effective in treating children having hypothalamic obesity by reducing excessive insulin secretion ([0002]). Chithambara teaches that the octreotide compound is dispersed throughout a PLGA polymer microsphere ([0007]). Chithambara teaches that the microsphere formulation is able to provide sustained release of the active agent from 15 days, one month or 2 months, where instant claim 13 recites 4-8 weeks (1-2 months). Regarding the microsphere d90 values as recited in claims 1, 8 and 9, Chithambara teaches that the octreotide loaded microspheres generally have a diameter from about 0.1 micron to about 500 micrometers, even more specifically from about 1 to about 200 microns ([0039]), thereby making obvious the claimed ranges. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). Regarding the amount of octreotide as recited in claims 10-12, Chithambara teaches that the microspheres comprise a “therapeutically effective amount of octreotide” which may range from about 5 mg to about 50 mg, more specifically in an amount from about 10 mg to about 30 mg, e,g., about 10 mg, about 20 mg, or about 30 mg ([0047]). Chithambara teaches that the microspheres had varying lactide content and used microspheres that had PLGA or PLA ([0056]). Chithambara teaches that the amount of lactide and glycolide content in the polymer as well as the molecular weight of the polymer affects the rate and duration of drug release from the polymer microsphere ([0087]-[0090]).
Chithambara does not teach that the microspheres are for weight loss and left gastric artery embolization and a ratio of PLA to PLGA from 40:60 to 60:40. These deficiencies are made up for in the teachings of Huang, Weiss and Kassab.
Huang teaches that octreotide promotes weight loss via suppression of intestinal MTP and apoB48 expression (title). Huang teaches that a high-fat diet will up-regulate intestinal apoB48, MTP and apoAIV expression which may result in increasing fat absorption and subsequently obesity (page 1264 Conclusion). Huang teaches that octreotide can improve insulin resistance by inhibiting inflammatory mediators and insulin release and then down-regulating the expression levels of apob48 and MTP which reduces fat absorption and leads to weight loss (page 1264 Conclusion). Huang provided testing data with octreotide with rats that indicated weight loss in an obese testing group (Tables 1 and 2).
Weiss teaches that aggressive therapies for obesity such as surgery are reserved for patients with a BMI of >40kg/m2 (making obvious the BMI of claim 4) and do result in weight loss, but that these treatments have problems such as significant morbidity and mortality and high expense (page 2 paragraph 2). Weiss teaches that a more minimally invasive technique for patients with obesity and obesity-related health conditions is trans-arterial embolization of the left gastric artery, which may be referred to as bariatric arterial embolization (page 2 paragraph 2). Weiss teaches that this technique involves embolization of the left gastric artery can induce sufficient ischemia to the mucosa of the gastric fundus to inhibit ghrelin production by cells which, in turn, can lead to weight loss (page 6 lines 1-5). Weiss teaches calibrated microspheres as an embolic agent and teaches that microspheres are able to pass through small caliber vessels (page 7 second paragraph). Weiss teaches an example where swine have undergone a bariatric arterial embolization process with 40 μm microspheres and exhibited decreased ghrelin levels and decreased weight gain compared to a control group (page 7 paragraph 2) and also teaches that microspheres have been used in human patients (page 9 paragraph 1), making obvious claim 2.
Kassab teaches that many studies have been done to encapsulate hydrophobic drugs in polymeric microspheres of PLA and PLGA (page 4275 paragraph 4). Kassab teaches the formation of microspheres with varying ratios of PLA and PLGA to check the effect of lactide and glycolide content and the effect of drug solubility on drug encapsulation and release (page 4275 2.2 Methods). Kassab utilized formulations PLA:PLGA ratios ranging from 500:0 to 0:500 (see page 4276 Table 1). Kassab teaches that the drug encapsulation and drug loading percentages varied with the lactide content present in the polymeric mixture which may be explained by the fact that PLA is more hydrophobic than PLGA due to the presence of the side methyl groups and can thus affect the efficiency of drug incorporation into the microsphere (page 4276 section 3). Kassab further teaches that the release rate of the drug is affected by the ratio of PLA and PLGA in the polymeric mixture.
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have formed a method of causing weight loss for treating obesity by introducing microspheres formed from PLGA or PLA and with a diameter from about 0.1 micron to about 200 micrometers and that carry a therapeutically effective amount (e.g 10, 20 or 30 mg) of octreotide and that embolize the left gastric artery where they subsequently release octreotide. Octreotide is drug that may be loaded into microspheres formed from PLA or PLGA for delivery to a patient, as taught by Chithambara. Octreotide has been used in treating children having hypothalamic obesity, as taught by Chithambara and octreotide has been shown to reduce fat absorption and led to weight loss, as taught by Huang. Thus, it would have been obvious to one of ordinary skill to use octreotide in a method of causing weight loss as it has been taught for this use previously. Embolization of the left gastric artery with microspheres is a known method of treating obesity, as taught by Weiss. Thus, one of ordinary skill would have a reasonable expectation of successfully treating obesity and causing weight loss by embolizing the left gastric artery with PLGA/PLA microspheres loaded with octreotide as both bariatric arterial embolization with microspheres and microspheres with octreotide are both known in the art as useful for treating obesity related conditions. Thus, all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would yield nothing more than predictable results to one of ordinary skill in the art. The strongest rationale for combining reference is a recognition, expressly or implicitly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent that some advantage or expected beneficial result would have been produced by their combination. In re Sernaker, 702 F.2d 989, 994-95, 217 USPQ 1, 5-6 (Fed. Cir. 1983). Thus, one of ordinary skill would have a reasonable expectation of success of forming a method for causing weight loss by combining the octreotide loaded PLGA/PLA microspheres and bariatric arterial embolization, as the embolization method and the microsphere composition have been previously taught to successfully treat obesity.
Additionally, it would have been obvious to one of ordinary skill in the art to have formed microspheres with a combination of PLA and PLGA polymers in a ratio of 45:55 for the embolization method made obvious by Weiss and Chithambara, through a process of routine experimentation. Combining PLA and PLGA to form microspheres is known based on the teachings of Kassab. Further, in view of the teachings of Chithambara that the amount of lactide and glycolide content in the polymer affects the rate and duration of drug release from the polymer microsphere, as well as the teachings of Kassab that drug encapsulation and loading into microspheres and the drug release rate are affected by the lactide content due to changes in the hydrophobic nature of the microsphere, the ratio of PLA to PLGA in the microsphere is an art-recognized result effective variable such that determining that should be 45:55 would be a matter of optimization through routine experimentation. "[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). It would be obvious to use a combination of PLA and PLGA for microspheres as they are well known in the art and one of ordinary skill would be able to determine the preferred ratio of the polymers in order to best meet the desired encapsulation/loading/release of octreotide from the microspheres.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by
the references.
Response to Arguments
Applicant's arguments filed 11 Aug 2025 have been fully considered but they are not persuasive. Applicant argues that the teachings of Huang regarding octreotide and its indication toward weight loss is based on rat data rather than human data (page 2 of remarks) and that the examiner has not established how the finding in rats reasonably correlates with expected human outcomes (page 3 of remarks). The examiner does not find this persuasive as it is common practice to use animal models, and specifically rodents, for predicting drug indications in humans. Establishing pharmacological and safety testing results prior to administration in human patients in clinical trials is common and serves to establish that one of ordinary skill in the art would see the connection between octreotide and weight loss as obvious. The applicant looks to teachings from Craig and Dimitri (NPL documents provided by the applicant on 17 Jan 2025) as proof that one of ordinary skill would have been led away from the instant invention where octreotide is used for weight loss (page 3 of remarks). The examiner does not find the statements by Dimitri regarding a 2005 clinical trial where hypothalamic obesity patients treated with octreotide did not show a significant difference in BMI from control patients as persuasive in overcoming the teachings from the applied prior art. Dimitri does not indicate that further testing should not be pursued with octreotide and the single study where the BMI was equivalent between the experimental and control groups is not sufficient to establish that octreotide would have been understood as not suitable for weight loss. Alternatively, the teachings provided by Craig and Dimitri can be understood to further support the case for obviousness as they indicate that octreotide is known to be associated with weight loss. A clinical trial where the results were neutral regarding weight loss may merely indicate that further research is needed regarding the appropriate administration of octreotide, but it does not sufficiently indicate to one of ordinary skill that octreotide should be disassociated from weight loss. Overall the examiner does not find the teachings of Craig and Dimitri as sufficient in overcoming the prima facie case of obviousness for a method of causing weight loss by administering polymer microspheres with octreotide as is obvious from the teachings of Chithambara in view of Huang, Weiss and Kassab as is described in the rejection above.
Conclusion
No claims are allowed.
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 extension fee 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 date of this final action.
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/E.C.M./Examiner, Art Unit 1619
/BENNETT M CELSA/Quality Assurance Specialist , Art Unit 1600