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 .
Response to Amendment
Applicant's response, filed 16 December 2025, has been received and entered.
Claims 1 and 6-7 have been amended, claims 2-5 have been canceled and claim 8 has been newly added. Claims 1 and 6-8 are currently pending.
The text of those sections of Title 35, U.S. Code not included in this action can
be found in a prior Office action.
Any objection or rejection of record which is not expressly repeated in this action
has been overcome by Applicant's response and withdrawn.
Applicant's arguments filed 16 December 2025 have been fully considered but are not found to be persuasive.
Priority
Applicant’s arguments regarding priority are persuasive. Any noted objection is withdrawn.
Drawings
The drawings remain objected to because they do not comply with 37 CFR 1.84(a)(1) and 37 CFR 1.84(b)(1) for the reasons set forth in the previous Office action.
Applicant asserts that replacement drawings have been filed (received 16 December 2025). However, while replacement drawings have been received, the noted deficiencies have not been remedied by the most recent submission.
The text remains blurry as solid black lines are not realized with the most recent submission. The lines in the drawings are not solid. See example below:
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The photographs in Figures 2 and 4 are not of sufficient quality so that all details in the photographs are reproducible and so that the distinctions which are supposed to be shown are not visible (see example below).
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The graph in Figure 5 is not clear and is not in black and white. The gray scale which is used does not meet the requirements of 37 CFR 1.84(a)(1). Applicant should note that there are error bars which do not appear to be attached to any bar (the bar for BMP10 is completely absent) because the “color” which is being approximated by the computer program translates it into nothing that is visible (see example below).
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Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The claims are not directed to pharmaceutical compositions.
Response to Argument
Applicant’s amended title has been received and entered, however, it does not correct the previously noted deficiency. The amended title is still directed to a pharmaceutical composition, which is not the invention of the instant application as defined by the claims.
Applicant’s replacement abstract has been received and entered. The abstract is still objected to because it does not contain a statement of that which is new in the art “to which the invention pertains”. The invention is defined by the claims and the claims are directed to methods and not to pharmaceutical compositions. Correction is still required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 1 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 has been amended to a “method of treating Type 2 diabetes” in a subject in need thereof”. However, this recitation is new matter. The instant specification at no point discloses the treatment of type 2 diabetes nor does it contemplate the treatment of type 2 diabetes. The specification mentions “diabetes” 10 different times, but fails to provide support for a claim to treatment of type 2 diabetes and therefore, the claim is new matter.
Response to Arguments
Applicant argues at page 9 of the response that while the term “Type 2 diabetes” is not explicitly recited in the specification, it is supported because Example 7 uses a high-fat-diet-induced obese mouse model, which is a standard model for type 2 diabetes because it exhibits obesity-associated insulin resistance. Applicant’s argument has been fully considered, but is not found persuasive. The animal model which is used in the instant specification is used for a number of different metabolic conditions and is not limited to the study of type 2 diabetes.
Claims 1 and 6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of reducing insulin resistance, does not reasonably provide enablement for treating type 2 diabetes or obesity in a subject as broadly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The instant specification, beginning at page 9, performed a number of different experiments utilizing BMP10. In Examples 1-2, the ability of BMP10 to induce brown adipocyte differentiation was investigated. The specification states that BMP10 promoted brown adipocyte differentiation of mouse embryonic mesenchymal cells or stem cells of the stromal vascular fraction isolated from subcutaneous adipose tissue (see page 10). BMP10 also induced expression of adipocyte differentiation markers (Example 3 at page 11), including Ucp1 which is a marker for brown fat. Example 6 shows an increase in BMP10 expression in the heart and blood of mice who were exercised for 4 weeks. Example 7 utilized a high-fat diet-induced obesity mouse model to study the effects of BMP10. The specification asserts that administration of BMP10 for 6 weeks resulted in “a tendency to decrease whole body fat mass”. In other words, the effect of BMP10 on body fat was not statistically significant. BMP10 administration did result in significantly lower fasting blood glucose which suggests an improvement in insulin resistance. BMP10 administration also significantly reduced total cholesterol. The specification then concludes that “BMP was effective in improving obesity, diabetes and dyslipidemia”.
Claims 1 and 6 are directed to methods of treating type 2 diabetes or obesity in a subject in need thereof by administering a pharmaceutical composition of BMP10. The disclosure of the instant specification does not support the treatment of type 2 diabetes or obesity in a subject in need thereof as the claims do not indicate what effects are to be achieved by the administration of BMP10 nor does the instant specification provide an expectation that administration of BMP10 in any/all subjects will result in a therapeutic benefit that results in treatment of the stated condition. For example, type 2 diabetes can have long term complications such as vision loss, heart disease, stroke and kidney damage. The instant specification does not enable treatment of type 2 diabetes which provides for restoration of vision, restoration of kidney function, etc. In order for the claimed method to be enabled for treatment of the stated conditions, the method would need to be therapeutic, meaning that the effects which are achieved would have a meaningful impact on the subject to be considered a treatment. For the treatment of obesity, the effect of the administration of BMP10 on the subject would need to provide a therapeutic effect on body weight because if not, it would not be considered a “treatment”.
With regard to treatment of obesity in humans, Marlatt et al. (Curr. Obes. Rep. 6: 389-396, 2017) teach that most studies on brown adipose tissue stimulation has been conducted in rodents (see abstract). Marlatt et al. teach that while a number of different conditions induce browning of subcutaneous fat in mice (such as exercise), browning of white adipose tissue has not been reproducible in humans (see page 391, column 1). Marlatt et al. teach that activation of BAT in humans improves insulin sensitivity, this activation does not result in observable weight loss (see page 319, column 2). Marlatt et al. conclude that there is no convincing evidence to indicate that BAT may be a viable pharmaceutical target for body weight loss or even weight loss maintenance (see abstract) largely due to the limited amount of BAT in humans (see paragraph spanning pages 392-393). Therefore, while the instant specification demonstrates a reduction in weight gain in a high-fat diet-induced obesity mouse model, this model is not predictive of weight loss in a human subject because humans do not have the BAT capacity of mice and even assuming maximum stimulation of BAT, weight loss in order to be considered a treatment of obesity would not be expected to be achieved in light of the teachings of Marlatt et al. (see page 393, first paragraph).
The examples which are presented in the instant specification are all performed on mice or on fat cells from mice. However, the results from the instant specification would not be considered predictive of outcomes in other species, such as humans, because fat cells from different species are not identical. Zuriaga et al. ((2017) Humans and Mice Display Opposing Patterns of “Browning” Gene Expression in Visceral and Subcutaneous White Adipose Tissue Depots. Front. Cardiovasc. Med. 4: 27) teach that caution should be applied in extrapolating the results of murine browning gene expression studies to human pathophysiology and that human adipose tissue does not respond to browning stimuli identified in mouse models (see abstract and page 4, column 1, last sentence of first paragraph). Additionally, fat cells from different species do not necessarily respond to stimuli in the same manner as evidenced by Zhang et al. (Factors Associated with White Fat Browning: New Regulators of Lipid Metabolism. Int. J. Mol. Sci. 2022, 23, 7641) which found that fucoxanthin activates brown fat and white fat browning in rodents, resulting in anti-obesity effects, but fucoxanthin failed to induce browning of human adipocytes (see page 12, first paragraph).
The instant specification provides evidence that BMP10 administration in mice results in a reduction in insulin resistance and a reduction in weight gain in mice fed a high fat diet compared to control mice. However, these effects do not support a broad claim to a method of treating type 2 diabetes or obesity in a subject in need thereof because the results of the experiments detailed in the specification cannot be extrapolated to other species, such as humans, because adipocytes from different species are different and do not respond similarly. While the level of skill in the art is high, it would require undue experimentation to practice the method as currently claimed because of the unpredictability in the art as well as the prior art teaching that the experimental model and tissues used are not predictive of other species, especially human tissue and therefore, the results presented in the instant specification cannot be extrapolated to other species with a reasonable expectation of success.
Response to Arguments
Applicant argues at pages 9-10 that BMP10 significantly inhibits weight gain, pointing to Figure 7(a). Applicant also provides a difference analysis of the data in Figure 7(a), showing the data as a percentage of weight gain. Applicant asserts at page 11 that BMP 10 had a significant effect in suppressing diet-induced obesity.
Applicant’s argument has been fully considered, but is not found persuasive. An inhibition of diet-induced weight gain in mice is not predictive of inducing weight loss in an obese subject. The two situations are not equivalent nor would one be predictive of the other, absent evidence to the contrary.
Applicant, beginning at page 11 of the response, cites several references in support of the assertion that human BAT is a viable and clinically relevant target in rebuttal of Marlatt et al., cited in the previous Office action.
Applicant cites Becher et al. (2021) as showing that BAT in humans is associated with a lower prevalence of cardiometabolic diseases and that beneficial effects of BAT were more pronounced in overweight/obese individuals. While the Becher et al. study is appreciated, Becher et al. also conclude (last paragraph of article) that their study indicates “that BAT has therapeutic potential in humans”, “the emergence of BAT as a potential therapeutic target is appealing” but “future research should aim to improve our understanding of BAT regulation in humans and to develop mechanisms to safely modulate BAT activity”. Therefore, Becher et al. as of 2021 concludes that utilization of BAT for therapeutic purposes had not been developed yet as its potential was appealing and further research was necessary to understand how it worked in humans and how to modulate its activity.
Applicant cites Cohen et al. (2015) as showing that adult human BAT shares molecular characteristics with “beige” fat. Applicant asserts that the instant specification demonstrates that BMP10 induces browning of SVF-derived adipocytes (similar to beige fat formation). Applicant concludes that the mechanism of BMP10 inducing browning/beiging is directly relevant to human physiology.
Applicant’s argument has been fully considered, but is not found persuasive. The mechanism of browning/beiging was taken into consideration in the previous response. Marlatt et al. teach that while a number of different conditions induce browning of subcutaneous fat in mice, browning of white adipose tissue has not been reproducible in humans (see page 39, column 1). Additionally, Zhang et al. (cited above) teach that fat cells from different species do not necessarily respond to stimuli in the same manner. The examples in the specification which Applicant is relying upon are exclusively from mice, but based on the prior art, mouse fat cells are not identical to human fat cells and they do not respond in a similar manner to the same stimuli. Zuriaga et al. (cited above) teach that caution should be applied in extrapolating the results of murine browning gene expression studies to human pathophysiology and that human adipose tissue does not respond to browning stimuli identified in mouse models (see abstract and page 4, column 1, last sentence of first paragraph).
Lastly, Applicant cites Carpentier et al. (2018) for the teaching that human BAT, when activated, contributes to energy expenditure and utilizes fatty acids and glucose. Applicant concludes that this teaching makes BMP10 as a therapeutic agent a plausible consideration. Applicant’s argument has been fully considered, but is not found persuasive. The teachings in the instant specification suggest that BMP10 has the potential to increase BAT activation and induce browning/beiging of WAT, however, the results of BMP10 in mice and murine adipocytes cannot be extrapolated to any other particular species, including humans, because the art clearly teaches that adipocytes from different species respond to different stimuli and while one stimuli may be successful in mice to induce browning/beiging, there is no reasonable expectation that the same stimuli will result in the induction of BAT or browning/beiging of WAT in humans.
Applicant’s arguments at page 13 address previous grounds of rejection and assert that amendments to the claims have been made to obviate the rejections. The rejection based on type 1 diabetes, dyslipidemia and health food has been avoided by the amendments to the claims.
Allowable Subject Matter
Claims 7-8 are allowed.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christine J Saoud whose telephone number is (571)272-0891. The examiner can normally be reached M-F, 8am-4pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Z Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Christine J Saoud/Primary Examiner, Art Unit 1645
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