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
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09 Apr 2026 has been entered.
Response to Amendment
Status of the Claims
Receipt of Applicant’s response, filed 09 Apr 2026 has been entered.
The claims under examination were filed 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 a 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 09 Apr 2026 have been fully considered but they are not persuasive. Applicant argues that Craig and Dimitri (NPL references provided by the applicant on 17 Jan 2025) would have steered one of ordinary skill away from the solution of the present invention (page 2 of remarks). Applicant argues that the clinical trial of Craig and summarized by Dimitri failed to show a significant difference in BMI due to octreotide and that this can only point away from concluding that octreotide causes a significant difference in BMI in humans and thus that this clinical trial teaches away from using octreotide to cause weight loss in a human subject (page 3 of remarks). Applicant argues that the clinical trial demonstrates that, in fact, octreotide is not associated with weight loss (page 3 of remarks).
The examiner does not find this persuasive. The combined teachings of Chithamabara, Huang, Weiss, and Kassab render obvious the limitations of the instant claims, specifically the use of octreotide microspheres for weight loss. Huang teaches that octreotide promotes weight loss and Chithambara teaches octreotide is useful for treating children having hypothalamic obesity by reducing excessive insulin secretion. Thus, there is a prima facie case of obviousness for using octreotide for weight loss and the teachings of Craig and Dimitri are not sufficient to overcome this case for obviousness. Dimitri is review article discussing various treatments for hypothalamic obesity. The section of Dimitri relevant to octreotide (page 5) is shown below.
PNG
media_image1.png
498
335
media_image1.png
Greyscale
The examiner notes that the study described at the bottom of the excerpt shown above citing reference 82 is referring to the clinical trial of Craig and Dimitri indicates that treatment with octreotide did not result in a difference from the placebo for this trial. This single study of Craig, summarized by Dimitri, is not sufficient to overcome the case of obviousness described above. In addition to the trial referred to by the applicant, Dimitri additionally refers to other tests in the excerpt above where octreotide demonstrated improvements in BMI in patients. Thus, from Dimitri it is clear that octreotide was known to be associated with weight loss and the single trial of Craig does not indicate that this indication would be completely dismissed. Dimitri does not provide further commentary that those of ordinary skill would have no longer pursued weight loss treatments with octreotide after the results of Craig were known. Drugs can be retested under new conditions or formulations after failing a trial and a single failing is not sufficient to teach away from the indication it is tested for. As further evidence to this point, the examiner notes that the clinical trial of Craig was performed in 2005, whereas the Chithambara, making the connection of treating hypothalamic obesity with octreotide, and Huang, which teaches octreotide promotes weight loss, were published in 2010 and 2013 respectively. These teachings were after the trial of Craig, further indicating that one of ordinary skill would not have understood the trial of Craig as teaching away from the obvious connection between octreotide and weight loss. Thus, the examiner is not persuaded by the applicant’s arguments that Craig and Dimitri provide sufficient teaching to overcome the prima facie case of obviousness presented.
Conclusion
No claim is allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EDWIN C MITCHELL whose telephone number is (571)272-7007. The examiner can normally be reached Mon-Fri 8:00-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Blanchard can be reached on (571)272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/E.C.M./Examiner, Art Unit 1619
/ANNA R FALKOWITZ/ Primary Examiner, Art Unit 1600
Prosecution Insights