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 .
Priority
This application is a 371 U.S. National Stage Entry of International Application No. PCT/IB2021/000629, filed September 15, 2021, which claims the benefit of U.S. Provisional Application No. 63/079,243, filed on September 16, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/20/2026 has been considered by the examiner.
Claims Status
Claims 1, 6, 8, 10, 13, 19, 27, 43, 51-55, 57, 61, and 64 are pending and under examination. Claims 2-5, 7, 9, 11-12, 14-18, 20-26, 28-42, 44-50, 56, 58-60, 62-63, and 65-68 are canceled.
Action Summary
Claims 1, 43, 51-55, 57, 61, and 64 rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ben-Sasson (WO2016/020919 A1), are withdrawn in light of the claim amendment (“replacing the compound of the formula (I) with its corresponding substituents with the specific compound of Formula (I)
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“and adding “wherein the plurality of injections is provided in a specific grid pattern which provides for injection spaced at 1 centimeter apart”.)
Claims 6, 8, 10, 13, 19, 27 rejected under 35 U.S.C. 103 as being unpatentable over Ben-Sasson (WO2016/020919 A1) cited as “Ben-Sasson-1” as applied to claims 1, 3, 6, 8, 10, 13, 19, 27-28, 33, 36, 41, 43, 51-55, 57, 61, and 64 in view of Ben-Sasson et al (US2014/0329877 A1) cited as “Ben-Sasson-2”, Sukkar (Kybella product specification, August 10, 2020 as cited by Archive.org), and Kythera Biopharmaceuticals Inc (BelKyra product monograph, 2018), are modified and revisited in light of the amendment to claim 1.
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.
Claims 1, 6, 8, 10, 13, 19, 27, 43, 51-55, 57, 61, and 64 are rejected under 35 U.S.C. 103 as being unpatentable over Ben-Sasson (WO2016/020919 A1) cited as “Ben-Sasson-1” in view of Ben-Sasson et al. (US2014/0329877 A1) cited as “Ben-Sasson-2”, Sukkar (Kybella product specification, August 10, 2020 as cited by Archive.org), and Kythera Biopharmaceuticals Inc (BelKyra product monograph, 2018).
Ben-Sasson-1 teaches a method of reducing the quantity of fat (adipose) tissue in as subject in this case pig in need thereof, comprising administering subcutaneously, two clusters of 5 injection sites, each 0.5 ml injection consists of (1) 5.6% w/w MTK-012, 10% w/w Tween 80, 57% w/w propylene glycol, 3% w/w benzyl alcohol, and 24.4% w/w water for a total of 100% w/w and; and (2) 0.56g or 560 mg MTK-012,
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,1 g or 1,000 mg, 5.7 g or 5,700 mg, 03 g or 300 mg, and or 2.4 g or 2,440 mg for a total of 10 g or 1000 mg to the pig’s flank. (See page5, examples 1and 2 and Table 1.) MTK-012 is the same compound claimed in claim 1. The amount of water is noted to be 24.4% w/w and the amount of MKT is also noted to be 5.6% w/w. Subcutaneous administration of 2 clusters of 5 injection sites to the Pig’s flank read plurality of injections into an adipose tissue portion of the abdomen. Ven-Sasson-1 teaches by reducing fat in subcutaneous tissue, it is meant to encompass reduction in thickness of adipose tissue. (See last paragraph of page 14 bridging first paragraph of page 15.) subcutaneous Moreover, Ben-Sasson-1 teaches this outstanding increase in temperature resulting in excessive thermogenesis is translated into a shrinkage of the subcutaneous fat as evident by the concave shape surface contours at the injected site 10 wks after local treatment, as depicted in Fig. 3. Propylene glycol reads on pharmaceutically acceptable excipient. Furthermore, Ben-Sasson-1 teaches the compound is used for use in the treatment of obesity. (See paragraph [0086].)
Ben-Sasson-1 does not teach specific grid pattern of more than 20 points. Ben-Sasson-1 does not teach plurality of injection comprises between 20 and 60 injections and a volume for each injection between about 25 to about 250 microliters. Ben-Sasson-1 does not also teach about 20 to about 100 mg/ml (claim 13) and the total dose of the compound per patient per sitting between about 0.5 to about 480 mg (claim 19) and about 5 to about 10 mg (claim 27). However, Ben-sasson-1 teaches the "effective amount" for purposes disclosed herein is determined by such considerations as may be known in the art. The amount must be effective to achieve the desired therapeutic effect as described above, depending, inter alia, on the type and severity of the disease to be treated and the treatment regime. The effective amount is typically determined in appropriately designed clinical trials (dose range studies) and the person versed in the art will know how to properly conduct such trials in order to determine the effective amount. As generally known, an effective amount depends on a variety of factors including the affinity of the compound to its target protein(s), its distribution profile within the body, a variety of pharmacological parameters such as half-life in the body, on undesired side effects, if any, on factors such as body-weight, BMI, age and gender, etc. (See third paragraph of page 18.)
Ben-Sasson-2 teaches an injection of 1 ml MTK-012 (=25 mg/kg) was performed as follows: the left side of the rat’s body was shaved and subcutaneous (s.c.) injections, 0.2 ml each, were administered at 5 sites, equally distributed along the left side of the rats. The rats were sacrificed after 3 weeks and inner part of their skin was examined. It is evident that the s.c. adipose tissue was reduced (visibly shown) in the treated rats (FIGS. 3B and 3D), as manifested by the exposure of the underneath blood vessels, as compared with the same anatomical area in FIGS. 3A and 3C. (See paragraph [0119].) The 0.2 ml can be converted to 200 µl.
Sukkar teaches Treatment with Kybella (deoxycholic acid) is fast and easy, similar to treatment with other cosmetic injectables. We can administer an anesthetic to ensure your comfort during treatment if you so desire. Then, we will administer between 20 and 30 small injections of Kybella in a grid pattern in the fatty zone. The entire process is completed in less than 30 minutes. (See third paragraph of page 5.)
Kythera Biopharmaceuticals Inc teaches Belkyra (deoxycholic acid) injection is used for improvement in the appearance of moderate to severe convexity or fullness associated with submental fat (SMF) in adults. (See second paragraph of page 3.) Moreover, Kythera Biopharmaceuticals Inc teaches Belkyra was administered as 50 injections of 2 mg/cm2 spaced on a 1 cm2 grid. (See Table 2 and Figure 2.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the MKT-012-adipose-reduction method taught by Ben-Sasson-1 by administering MTK-012 according to the known multi-injection grid-based adipolytic administration protocol taught byKytera Biopharmaceuticals Inc., including injections spaced about 1-cm apart, injection volumes of about 0.2 ml (200 µL), and a plurality of injections distributed throughout the treatment area, because Kythera teaches such administration parameters improve delivery of adipolytic agents throughout localized subcutaneous fat deposits for cosmetic fat reduction.
One would have been motivated to do so because Ben-Sasson-1 already teaches MTK-012 reduces subcutaneous adipose tissue, while Kythera teaches a clinically effective injection technique for localized adipose reduction using multiple injections arranged on a 1-cm grid throughout the treatment area. Thus, a person of ordinary skill in the art would have recognized the claimed injection spacing, injection volume, and multiple-injection grid pattern as result-effective variables governing distribution of adipolytic compounds within subcutaneous adipose tissue would have optimized such parameters through routine experimentation.
One of ordinary skill in the art would have had a reasonable expectation of success because both Ben-Sasson-1 and Kythera teach successful reduction of localized subcutaneous fat through subcutaneous administration of adipolytic agents directly into adipose tissue. Therefore, applying Kythera’s known injection protocol to the MKT-012 composition of Ben-Sasson-1 would have predictably resulted in successful reduction of adipose tissue volumne or thickness.
are pending and under examination. Claims 2-5, 7, 9, 11-12, 14-18, 20-26, 28-42, 44-50, 56, 58-60, 62-63, and 65-68 are canceled.
Action Summary
Claims 1, 43, 51-55, 57, 61, and 64 rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ben-Sasson (WO2016/020919 A1), are withdrawn in light of the claim amendment (“replacing the compound of the formula (I) with its corresponding substituents with the specific compound of Formula (I)
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“and adding “wherein the plurality of injections is provided in a specific grid pattern which provides for injection spaced at 1 centimeter apart”.)
Claims 6, 8, 10, 13, 19, 27 rejected under 35 U.S.C. 103 as being unpatentable over Ben-Sasson (WO2016/020919 A1) cited as “Ben-Sasson-1” as applied to claims 1, 3, 6, 8, 10, 13, 19, 27-28, 33, 36, 41, 43, 51-55, 57, 61, and 64 in view of Ben-Sasson et al (US2014/0329877 A1) cited as “Ben-Sasson-2”, Sukkar (Kybella product specification, August 10, 2020 as cited by Archive.org), and Kythera Biopharmaceuticals Inc (BelKyra product monograph, 2018), are modified and revisited in light of the amendment to claim 1.
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.
Claims 1, 6, 8, 10, 13, 19, 27, 43, 51-55, 57, 61, and 64 are rejected under 35 U.S.C. 103 as being unpatentable over Ben-Sasson (WO2016/020919 A1) cited as “Ben-Sasson-1” in view of Ben-Sasson et al. (US2014/0329877 A1) cited as “Ben-Sasson-2”, Sukkar (Kybella product specification, August 10, 2020 as cited by Archive.org), and Kythera Biopharmaceuticals Inc (BelKyra product monograph, 2018).
Ben-Sasson-1 teaches a method of reducing the quantity of fat (adipose) tissue in as subject in this case pig in need thereof, comprising administering subcutaneously, two clusters of 5 injection sites, each 0.5 ml injection consists of (1) 5.6% w/w MTK-012, 10% w/w Tween 80, 57% w/w propylene glycol, 3% w/w benzyl alcohol, and 24.4% w/w water for a total of 100% w/w and; and (2) 0.56g or 560 mg MTK-012,
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,1 g or 1,000 mg, 5.7 g or 5,700 mg, 03 g or 300 mg, and or 2.4 g or 2,440 mg for a total of 10 g or 1000 mg to the pig’s flank. (See page5, examples 1and 2 and Table 1.) MTK-012 is the same compound claimed in claim 1. The amount of water is noted to be 24.4% w/w and the amount of MKT is also noted to be 5.6% w/w. Subcutaneous administration of 2 clusters of 5 injection sites to the Pig’s flank read plurality of injections into an adipose tissue portion of the abdomen. Ven-Sasson-1 teaches by reducing fat in subcutaneous tissue, it is meant to encompass reduction in thickness of adipose tissue. (See last paragraph of page 14 bridging first paragraph of page 15.) subcutaneous Moreover, Ben-Sasson-1 teaches this outstanding increase in temperature resulting in excessive thermogenesis is translated into a shrinkage of the subcutaneous fat as evident by the concave shape surface contours at the injected site 10 wks after local treatment, as depicted in Fig. 3. Propylene glycol reads on pharmaceutically acceptable excipient. Furthermore, Ben-Sasson-1 teaches the compound is used for use in the treatment of obesity. (See paragraph [0086].)
Ben-Sasson-1 does not teach specific grid pattern of more than 20 points. Ben-Sasson-1 does not teach plurality of injection comprises between 20 and 60 injections and a volume for each injection between about 25 to about 250 microliters. Ben-Sasson-1 does not also teach about 20 to about 100 mg/ml (claim 13) and the total dose of the compound per patient per sitting between about 0.5 to about 480 mg (claim 19) and about 5 to about 10 mg (claim 27). However, Ben-sasson-1 teaches the "effective amount" for purposes disclosed herein is determined by such considerations as may be known in the art. The amount must be effective to achieve the desired therapeutic effect as described above, depending, inter alia, on the type and severity of the disease to be treated and the treatment regime. The effective amount is typically determined in appropriately designed clinical trials (dose range studies) and the person versed in the art will know how to properly conduct such trials in order to determine the effective amount. As generally known, an effective amount depends on a variety of factors including the affinity of the compound to its target protein(s), its distribution profile within the body, a variety of pharmacological parameters such as half-life in the body, on undesired side effects, if any, on factors such as body-weight, BMI, age and gender, etc. (See third paragraph of page 18.)
Ben-Sasson-2 teaches an injection of 1 ml MTK-012 (=25 mg/kg) was performed as follows: the left side of the rat’s body was shaved and subcutaneous (s.c.) injections, 0.2 ml each, were administered at 5 sites, equally distributed along the left side of the rats. The rats were sacrificed after 3 weeks and inner part of their skin was examined. It is evident that the s.c. adipose tissue was reduced (visibly shown) in the treated rats (FIGS. 3B and 3D), as manifested by the exposure of the underneath blood vessels, as compared with the same anatomical area in FIGS. 3A and 3C. (See paragraph [0119].) The 0.2 ml can be converted to 200 µl.
Sukkar teaches Treatment with Kybella (deoxycholic acid) is fast and easy, similar to treatment with other cosmetic injectables. We can administer an anesthetic to ensure your comfort during treatment if you so desire. Then, we will administer between 20 and 30 small injections of Kybella in a grid pattern in the fatty zone. The entire process is completed in less than 30 minutes. (See third paragraph of page 5.)
Kythera Biopharmaceuticals Inc teaches Belkyra (deoxycholic acid) injection is used for improvement in the appearance of moderate to severe convexity or fullness associated with submental fat (SMF) in adults. (See second paragraph of page 3.) Moreover, Kythera Biopharmaceuticals Inc teaches Belkyra was administered as 50 injections of 2 mg/cm2 spaced on a 1 cm2 grid. (See Table 2 and Figure 2.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the MKT-012-adipose-reduction method taught by Ben-Sasson-1 by administering MTK-012 according to the known multi-injection grid-based adipolytic administration protocol taught byKytera Biopharmaceuticals Inc., including injections spaced about 1-cm apart, injection volumes of about 0.2 ml (200 µL), and a plurality of injections distributed throughout the treatment area, because Kythera teaches such administration parameters improve delivery of adipolytic agents throughout localized subcutaneous fat deposits for cosmetic fat reduction.
One would have been motivated to do so because Ben-Sasson-1 already teaches MTK-012 reduces subcutaneous adipose tissue, while Kythera teaches a clinically effective injection technique for localized adipose reduction using multiple injections arranged on a 1-cm grid throughout the treatment area. Thus, a person of ordinary skill in the art would have recognized the claimed injection spacing, injection volume, and multiple-injection grid pattern as result-effective variables governing distribution of adipolytic compounds within subcutaneous adipose tissue would have optimized such parameters through routine experimentation.
One of ordinary skill in the art would have had a reasonable expectation of success because both Ben-Sasson-1 and Kythera teach successful reduction of localized subcutaneous fat through subcutaneous administration of adipolytic agents directly into adipose tissue. Therefore, applying Kythera’s known injection protocol to the MKT-012 composition of Ben-Sasson-1 would have predictably resulted in successful reduction of adipose tissue volume or thickness.
Acknowledgement is made of the receipt and entry of Applicant’s remarks/arguments filed on March 20, 2026.
Applicant argues that neither Ben-Sasson-1 nor Ben-Sasson-2 teaches a plurality of injection provided in a specific grid pattern with injections spaced 1-cm apart and further relies on upon the declaration by Dr. Blaugrund alleging unexpected resulted associated with the claimed injection spacing.
Applicant’s arguments have been fully considered but are not persuasive. Specifically, Kythera Biopharmaceuticals Inc. expressly teaches applying “1-cm injection grid to mark the injection sites” and further teaches “inject a dose of 0.2 mL into each site, 1-cm part.” Thus, the cited art expressly teaches the claimed grid pattern and 1-cm injection spacing.
Applicant further argues that one of ordinary skill in the art would not have combined the teachings relative to deoxycholic acid with the MTK-012 compound of Ben-Sasson-1 because the compounds possess different chemical structure. However, the rejection does not rely upon substituting deoxycholic acid for MTK-012. Rather, Kythera Biopharmaceuticals Inc. and Sukkar are relied upon solely for their teachings regarding known adipolytic injection administration protocol, including multiple injections arranged in a 1-cm grid pattern for localized reduction of subcutaneous fat tissue. One of ordinary skill in the art would have recognized that injection spacing, injection volume, injection distribution across a treatment area constitutes result-effective variables governing local distribution of adipolytic agents within subcutaneous adipose tissue. Ben-Sassaon -1itself expressly teaches that effective treatment regimens and dosage may be optimized depending upon the desired therapeutic effect. Therefore, applying the known grid-based adipolytic injection protocol taught by Kytera to the known MTK-012 adipose reduction method of Ben-Sasson-1 would have constituted no more than routine optimization and application of a known administration technique to a known adipolytic agent.
Applicant’s declaration evidence is also not persuasive of unexpected results because the alleged improvement in subcutaneous fat reduction is not reasonably attributable solely to the claimed 1-cm injection spacing. As shown in the Declaration,
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Cohort 4 differs from Cohort 2 and 3 not only in injection spacing, but also in total dose and number of injections administered. Specifically, Cohort 4 utilized 180 mg and 36 injections at 1-cm spacing, whereas Cohort 3 utilized 120 mg and 24 injections at 2-cm spacing. Accordingly, multiple variables were changed simultaneously, such that the declaration fails to establish that the alleged improvement was caused specifically by the claimed 1-cm injection spacing rather than increased dosage and increased injection number.
Moreover, MPEP 716.02(d) states “whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980).” In the present case, the claims are broad and encompass numerous injection numbers, dosages, concentrations, adipose treatment sites, and pharmaceutical excipients, whereas the declaration is limited to a particular study protocol involving specific dosing regiments, and cohorts. Therefore, the proffered evidence is not commensurate in scope with the breadth of the pending claims. Furthermore, although the declaration identifies the active ingredient utilized in the study, the declaration does not sufficiently establish whether the pharmaceutical compositions administered across the cohorts were otherwise identical in formulation, including the identity and amounts of excipients, solvents, surfactants, or other formulation components that may affect delivery, tissue distribution, or adipolytic activity of the administered compound. In fact, the specification disclosed three formulations:
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And each exhibits different pharmacokinetics contents. Thus, it is not clear whether the alleged improvement in efficacy in attributable solely to the claimed injection spacing.
Conclusion
Claims 1, 6, 8, 10, 13, 19, 27, 43, 51-55, 57, 61, and 64 are not allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JEAN P CORNET/ Primary Examiner, Art Unit 1628
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