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, 13, 16, 18, 21, 23, 30, 33 and 37-38 are pending. Claims 1, 13, 16, 18, 21, 23, 30, 33 and 37-38 are rejected.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/17/2026 has been entered.
Response to Arguments
Applicant traverses the obviousness rejections over Dagan et al. in view of Salam, Herskovitz and Ben-Sasson arguing that the instant compound and triamcinolone have significant structural differences and would not necessarily be expected to have the same therapeutic effect. This argument with respect to the nature the compounds is persuasive however, Dagan et al. teach that the prior art composition may be administered with additional helpful therapeutic agents. A person of ordinary skill seeking to treat various types of lipomas including angiolipomas would have been motivated to combine the compound of Dagan et al. which causes fat atrophy with an additional agent such as triamcinolone that is useful for treating the same condition and is capable of improving symptoms that may not be ameliorated by the prior art compound alone. Regarding the new limitations wherein the method of treating alleviates angiolipoma-associated pain, Dagan et al. teach administration within the claimed dosage range so there is a reasonable expectation of success that this effect would be achieved by the prior art method. The fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
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.
Claims 1, 21, 23, 27, 30, 33 and 37-38 are rejected under 35 U.S.C. 103 as being unpatentable over WO2013072915A1 by Dagan et al. in view of Salam. Am Fam Physician. 2002;65(5):901-905. and Herskowitz et al. Am J Clin Dermatol 2012; 13 (4): 273-274.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Dagan et al. teach “tricyclic compounds, compounds comprising them and uses thereof” (title). The prior art discloses the following compound which is identical to the compound of claim 1 (pages 6-7):
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Dagan et al. note that the prior art compound may be formulated in a pharmaceutical for parenteral administration such as subcutaneous administration and report that the compound is useful for treating conditions relating to abnormal fat distribution including lipomas as required by instant claims 1, 21, and 30 (pages 12 and 15).
Regarding instant claims 23 and 33, the prior art discloses a treatment example wherein the subject was administered a 1mL dosage of MTK-012 via subcutaneous injection (page 23, Example 7).
Regarding the limitation of claim 1 wherein administering the pharmaceutical composition to the subject alleviates angiolipoma-associated pain, this effect would naturally flow from the method of the prior art which teaches administration of the compound within the instant claimed range. The same rationale applies to claims 37 and 38 which recite a reduction of the angiolipoma-associated pain by at least about 42% as determined by the comparative pain scale.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art discloses methods of treating lipomas generically by administering a pharmaceutical composition comprising the compounds above but does not specify that the lipoma is an angiolipoma.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
In a review about office procedures for lipomas Salam reports (abstract):
Lipomas are adipose tumors that are often located in the subcutaneous tissues of the head, neck, shoulders, and back. Lipomas have been identified in all age groups but usually first appear between 40 and 60 years of age. These slow-growing, nearly always benign, tumors usually present as nonpainful, round, mobile masses with a characteristic soft, doughy feel. Rarely, lipomas can be associated with syndromes such as hereditary multiple lipomatosis, adiposis dolorosa, Gardner’s syndrome, and Madelung’s disease. There are also variants such as angiolipomas, neomorphic lipomas, spindle cell lipomas, and adenolipomas. Most lipomas are best left alone, but rapidly growing or painful lipomas can be treated with a variety of procedures ranging from steroid injections to excision of the tumor.
Salam teaches that steroid injections are one of the non-excisional treatments of lipomas and result in fat atrophy (page 902).
Herskowitz et al. report the treatment of two cases of angiolipoma with the corticosteroid injection triamcinolone. On page 273, the prior art provides a motivation for resorting to alternative modes of treatment, stating:
Standard treatment for non-infiltrating angiolipomas is total surgical removal.[1,2] Surgical excision is curative, and there is no evidence of malignant transformation.[3] Because of the presence of multiple lesions, and the desire to avoid scars our patients requested non-excisional corticosteroid injections.
Herskowitz et al. state that patients reported a decrease in size and pain of the lesions and suggest that success in treatment may be because corticosteroid injections result in local fat atrophy, thus shrinking the angiolipoma.
Dagan et al. reported that subcutaneous injection of MTK-012 resulted in a decrease in adipose or fat tissue and teach that the prior art composition may comprise additional useful therapeutic agents (page 12). Accordingly, a person of ordinary skill seeking to treat angiolipomas without the undesired effects of traditional surgical removal would have been motivated to administer compositions capable of inducing fat atrophy as taught by Salam and Herskowitz et al. such as the prior art compounds of Dagan et al. in combination with a steroid such as triamcinolone to improve therapeutic outcomes. Regarding the motivation to combine two agents disclosed for treatment of lipomas, MPEP 2144.06 (I) states:
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)
Claims 13, 16 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over WO2013072915A1 by Dagan et al. in view of Salam. Am Fam Physician. 2002;65(5):901-905. and Herskowitz et al. Am J Clin Dermatol 2012; 13 (4): 273-274. as applied to claims 1, 21, 23, 27, 30, 33 and 37-38 above, and further in view of WO 2016/020919 A1 by Ben-Sasson.
The combined teachings of Dagan et al., Salam and Herskowitz et al. disclose a method of treating angiolipomas by administering a pharmaceutical composition comprising the instant compound in addition to a steroid such as triamcinolone; however, the prior art does not specify the water content of the pharmaceutical composition.
Ben-Sasson discloses pharmaceutical compositions comprising compounds including MTK-012, MTK-013 of Dagan et al. which are embraced by the instant formula (page 5). Regarding instant claims 13, 16 and 18, Ben-Sasson teaches formulations where the water content is between 0% and 30% of the total composition weight which overlaps with the claimed ranges. Accordingly, a person of ordinary skill seeking to treat subject in the combined method of Dagan et al., Salam, and Herskowitz et al. would have been motivated to prepare the pharmaceutical composition using known formulations comprising the prior art compounds.
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 1, 13, 16, 18, 21, 23, 30, 33, and 37-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12097179 in view of WO2013072915A1 by Dagan et al., Salam. Am Fam Physician. 2002;65(5):901-905., Herskowitz et al. Am J Clin Dermatol 2012; 13 (4): 273-274. and WO 2016/020919 A1 by Ben-Sasson.
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 8 of the patent discloses a pharmaceutical composition comprising 3-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpropan-1-aminium which is disclosed by Dagan et al. A person of ordinary skill seeking to administer the pharmaceutical composition of the patent would have been motivated to explore known treatment methods comprising administering the compound which serves as the basis of a rejection under 35 USC 103. The teachings and rationale of Dagan et al., Salam, Herskowitz et al. and Ben-Sasson relative to instant claims 1, 13, 16, 18, 21, 23, 30, 33, and 37-38 are incorporated here by reference. The instant claims are deemed to be variants of the subject matter of the patent for the same reasons as under 35 USC 103.
Claims 1, 13, 16, 18, 21, 23, 30, 33 and 37-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 17, 19, 22, 24-25, 30 and 32-36 of copending Application No. 17642153 in view of WO2013072915A1 by Dagan et al., Salam. Am Fam Physician. 2002;65(5):901-905., Herskowitz et al. Am J Clin Dermatol 2012; 13 (4): 273-274. and WO 2016/020919 A1 by Ben-Sasson.
Although the claims at issue are not identical, they are not patentably distinct from each other because copending claim 1 generically discloses a method of treating a solid tumor by administering a pharmaceutical composition comprising 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium. Salam teaches that lipomas are adipose tumors and Dagan et al. disclose pharmaceutical compositions comprising the copending compound. A person of ordinary skill seeking to administer the pharmaceutical composition of the copending claims would have been motivated to explore known treatment methods comprising administering the compounds noted above which serves as the basis of a rejection under 35 USC 103. The teachings and rationale of Dagan et al., Salam, Herskowitz et al. and Ben-Sasson relative to instant claims 1, 13, 16, 18, 21, 23, 30, 33 and 37-38 are incorporated here by reference. The instant claims are deemed to be variants of the subject matter of the copending application for the same reasons as under 35 USC 103.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 13, 16, 18, 21, 23, 30, 33 and 37-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 8, 10, 13, 19, 27, 43, 51-55, 57, 61 and 64 of copending Application No. 18245132 in view of WO2013072915A1 by Dagan et al., Salam. Am Fam Physician. 2002;65(5):901-905., Herskowitz et al. Am J Clin Dermatol 2012; 13 (4): 273-274. and WO 2016/020919 A1 by Ben-Sasson.
Although the claims at issue are not identical, they are not patentably distinct from each other because copending claim 1 discloses a method of reducing adipose tissue by administering a pharmaceutical composition comprising 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium which is disclosed by Dagan et al. A person of ordinary skill seeking to administer the pharmaceutical composition of the copending claims would have been motivated to explore known treatment methods comprising administering the compound which serves as the basis of a rejection under 35 USC 103. The teachings and rationale of Dagan et al., Salam, Herskowitz et al. and Ben-Sasson relative to instant claims 1, 13, 16, 18, 21, 23, 30, 33, and 37-38 are incorporated here by reference. The instant claims are deemed to be variants of the subject matter of the copending application for the same reasons as under 35 USC 103.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 13, 16, 18, 21, 23, 30 and 33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-7, 10, 15-18, 20, 22-24, 34-36, 38-40 and 45-46 of copending Application No. 18292797 in view of WO2013072915A1 by Dagan et al., Salam. Am Fam Physician. 2002;65(5):901-905., Herskowitz et al. Am J Clin Dermatol 2012; 13 (4): 273-274. and WO 2016/020919 A1 by Ben-Sasson.
Although the claims at issue are not identical, they are not patentably distinct from each other because copending claim 20 discloses a method of treating lipoma pain by administering a pharmaceutical composition comprising 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium which is disclosed by Dagan et al. In the prior art, Herskowitz et al. describe the angiolipomas of the patients as painful nodules and painful lesions and report that following treatment there was a decrease in pain (page 273). A person of ordinary skill seeking to administer the pharmaceutical composition of the copending claims would recognize that treatments for lipomas which result in local fat atrophy have been successful in treating both lipomas and angiolipomas. As such one would be motivated to explore known methods of treating lipoma pain in patients with angiolipoma pain by administering the copending compound which serves as the basis of a rejection under 35 USC 103. The teachings and rationale of Dagan et al., Salam, Herskowitz et al. and Ben-Sasson relative to instant claims 1, 13, 16, 18, 21, 23, 30, 33, and 37-38 are incorporated here by reference. The instant claims are deemed to be variants of the subject matter of the copending application for the same reasons as under 35 USC 103.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 13, 16, 18, 21, 23, 30 and 33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of copending Application No. 18497531 in view of WO2013072915A1 by Dagan et al., Salam. Am Fam Physician. 2002;65(5):901-905., Herskowitz et al. Am J Clin Dermatol 2012; 13 (4): 273-274. and WO 2016/020919 A1 by Ben-Sasson.
Although the claims at issue are not identical, they are not patentably distinct from each other because copending claim 15 discloses a method of treating lipomas by administering a crystalline salt of 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium. Dagan et al. disclose methods of treating lipomas comprising administering 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium and salts thereof. A person of ordinary skill seeking to administer the crystalline compound of the copending claims would have been motivated to explore known treatment methods comprising administering the compound which serves as the basis of a rejection under 35 USC 103. The teachings and rationale of Dagan et al., Salam, Herskowitz et al. and Ben-Sasson relative to instant claims 1, 13, 16, 18, 21, 23, 30, 33 and 37-38 are incorporated here by reference. The instant claims are deemed to be variants of the subject matter of the copending application for the same reasons as under 35 USC 103.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/A.A.C./Examiner, Art Unit 1626
/MATTHEW P COUGHLIN/Primary Examiner, Art Unit 1626