DETAILED ACTION
Status of Application
The response filed 02/16/2026 has been received, entered and carefully considered. The response affects the instant application accordingly:
Claim 4 has been cancelled.
Applicant had previously elected Group I in response to restriction requirement and elected the species to be intravenous for the examination. Upon review the election of species is expanded to include any form that is a solution/liquid.
Due to restriction, based on election of Group I, claims 5-8, 13, 18 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claims 1, 3, 5-9, 11-18 are pending.
Claims 1, 3, 9, 11-12, 14-17 are present for examination at this time.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
All grounds not addressed in the action are withdrawn or moot as a result of amendment.
Standing Grounds of Rejection
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, 3-4, 9, 11-12, 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Saettone et al. (U.S. Pat. 6346273) in view of Majeed et al. (U.S. Pat. Pub. 2005/0051483).
Rejection:
Saettone et al. teaches an pharmaceutical aqueous solution comprising a pharmaceutical poorly water soluble active like forskolin, that is in a complex with a nonionic polymer such as PVP and a surfactant (abstract, Col. 5 line 60- Col. 6 line 3, Col. 8 line 7-15). The molecular weight of the PVP can be from 2000-1,500,000 (2kDa-1500kDa) preferably 2000-55,000 (2kDa-55kDa, Col. 5 line 66-Col. 6 line 3). The molar ratio of the active and complexing polymer if from about 1:0.1-about 1:100 and in the specific case of PVP the molar ratios vary from 1:0.25-1:7.5 (molar ratio/mass fraction, Col. 6 line 50-60). Forskolin is exemplified in a complex with PVP with a MW of 10,000 (10 kDa=10kD) with improved solubility without and with surfactant at 30% (30%w/w=30g/100ml= 300mg/ml), and Saettone et al. teaches that other conventional formulative ingredients suitable for the use of the product considered may be added to the solution (Table, Col. 8 line 45-50 and 61-Col. 9 line 18); Saettone et al. also exemplified a solution composition comprising forskolin with PVP (molecular weight of 10,000=1kDa, Example 12, Col. 11 line 20-30, see full document specifically areas cited).
Saettone et al. does not expressly teach the inclusion of 7-deacetyl-forskolin (7-DAFSK) but does teach aqueous solutions comprising a poorly water soluble active like forskolin where the solubility is improved by being in a complex with PVP.
Majeed et al. teaches known diterpenes like forskolin and 7-deacetylforkolin and their congeners/analogs/derivatives of natural or synthetic origin are known to be water insoluble and would benefit from solubilizing them in water(improve their solubility, claim 1, [4, 24]).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to formulate the aqueous PVP composition with 7-deacetyl-forskolin (7-DAFSK) as suggested by Majeed et al. and produce the claimed invention; as Saettone et al. teaches an aqueous solution comprising a poorly water soluble active like forskolin - in a complex with PVP as exemplified at 10 kDa, it would be obvious to incorporate a water insoluble active that is forskolin congener/analog like 7-deacetyl-forskolin as established by Majeed et al. as simple substitution of one water insoluble active (forskolin congener/analog) for another (forskolin congener/analog) is prima facie obvious with a reasonable expectation of success absent evidence of criticality for the forskolin congener/analog.
It is noted that the instant claim 3 is set forth in the form of product-by-process claim, which are considered product claims by the Office, it is noted that Majeed teaches that it can be from natural or synthetic origin. Applicants are reminded that process limitations cannot impart patentability to a product that is not patentably distinguished over the prior art. In re Thorpe et al. (CAFC 1985), supra; In re Dike (CCPA 1968) 394 F2d 584, 157 USPQ 581; Tri-Wall Containers, Inc. v. United States et al. (Ct Cls 1969) 408 F2d 748, 161 USPQ 116; In re Brown et al. (CCPA 1972) 450 F2d 531, 173 USPQ 685; Ex parte Edwards et al. (BPAI 1986) 231 USPQ 981. While the prior art does not teach the exact claimed values for the amount of 7-deacetyl-forskolin (7-DAFSK) in the complex with PVP, it does overlap as Saettone et al. teaches the range can be from 1:0.25-1:7.5 of active:PVP (1:1 is 50%, 1:0.25=4:1=80%) wherein even a slight overlap establishes a prima facie case of obviousness with a reasonable expectation of success absent evidence of criticality for the range. As the structural components of the composition are met, the composition properties and capacity for use (i.e. intravenous use) being pharmaceutically acceptable are also expected to be present as products of identical or substantially identical chemical composition cannot have mutually exclusive properties.
Response to Arguments:
Applicant's arguments center on the assertions that the rational for combining the Saettone and Majeed is the assumption that forskolin and its analog behave chemically in a similar way but that Example 6 of the instant specification demonstrates that forskolin cannot form a detectable complex with PVP while 7-DAFSK can form stable complexes with PVP with significant mass fraction with improved water solubility with the assertion that the improved water solubility is unexpected as if was up to three time higher than the non-complected form.
This is fully considered but not persuasive.
Example 6 of the specification is not representative of the prior art nor evidence of Applicant’s assertion. Example 6 is Applicant’s solution process with forskolin and PVP which did not form a detectable complex with forskolin but did with 7-deacetylforkolin, but the prior art process of Saettone et al. shows that it did form a detectable complex forskolin and PVP as it is designed for water insoluble actives - wherein it was successful with the forskolin and there is a reasonable expectation of success that it would successful with another water insoluble active and simple substitution of one water insoluble active (forskolin congener/analog) for another (forskolin congener/analog) is prima facie obvious with a reasonable expectation of success absent evidence of criticality for the forskolin congener/analog 7-deacetyl-forskolin (7-DAFSK) and PVP which has not been presented. As for Applicant’s assertion for unexpected results that the improved water solubility is unexpected as if was up to three times higher than the non-complexed form, this is not persuasive as Saettone et al. teaches that the complex has improved solubility of the water insoluble active including forskolin which was also at least 3 times greater than the non-complexed form wherein the improved solubility of the water insoluble active (i.e. simple substitution of forskolin congener/analog for another like R-DAFSK) is prima facie obvious with a reasonable expectation of success absent evidence of criticality for the compound or evidence that the product by process of heating the PVP above the glass transition temperature produces a patentably different product over a solution process and the prior art.
Accordingly, the rejection stands.
Claims 1, 3, 9, 11-12, 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Majeed et al. (WO 2005/025500) in view of Rowe et al. (Povidone).
Rejection:
Majeed et al. teaches pharmaceutical aqueous solutions comprising water insoluble diterpenes like forskolin and 7-deacetyl-forskolin (7-DAFSK) of natural or synthetic origin, with cyclodextrins and excipients such as viscosity agents like PVP for topical and systemic use (claim 1, abstract, [1, 37]). The amount of diterpenes in solution is from 0.09-6% (claim 4, see full document specifically areas cited).
While Majeed et al. does not teach the exact claimed values for concentration of diterpenes (i.e. 7-DAFSK), they do overlap wherein even a slight overlap in ranges establishes a prima facie case of obviousness, as a means of optimizing the amount of 7-DAFSK/diterpene to attain the desired therapeutic profile with a reasonable expectation of success absent evidence of criticality for the claimed range.
Majeed et al. does not expressly recite the molecular weight of the PVP but does teach its inclusion.
Rowe et al. teaches that povidone (PVP) comes in a range of molecular weights from 2500-3,000,000 (2.5-3000 kDa, Table 1).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to formulate the aqueous 7-deacetyl-forskolin composition with cyclodextrin and PVP within the molecular range as suggested by Rowe et al. and produce the claimed invention; as it is prima facie obvious to incorporate the PVP at its known molecular weight range and optimize within the molecular weight range to attain the desired therapeutic profile with a reasonable expectation of success absent evidence of criticality for the claimed values. As the structural components of the composition are met, the composition properties and capacity for use (i.e. intravenous use) being pharmaceutically acceptable are also expected to be present as products of identical or substantially identical chemical composition cannot have mutually exclusive properties. Additionally, as the same structural components are present, the PVP and 7-deacetyl-forskolin would naturally form a complex as demonstrated by the specification in the range recited (i.e. about 24% mass fraction with PVP of MW 2.5kDa, about 8% mass fraction with PVP of MW about 24 kDa)
Response to Arguments:
Applicant's arguments centers on the assertions that Majeed teaches solubility improvement with cyclodextrins not PVP and does not address mass fraction ranges or molecular weight optimization with PVP while the instant invention has 7-DAFSK complex with higher water solubility that is up to 3x greater than non-complexed forms, that Rowe is only teaching PVP as a pharmaceutical excipient, and that Majeed and Rowe cannot be combined as forskolin and its analog cannot be assumed to behave in a similar fashion.
This is fully considered but not persuasive.
The assertion that Majeed teaches improving solubility with cyclodextrins and not PVP is not persuasive as the claims are open (“comprising”) and does not preclude the presence of additional components like cyclodextrin. The assertion that Majeed does not address mass fraction ranges or molecular weight optimization with PVP is not persuasive as two structural components being present in solution and naturally forming the 7-DAFSK-PVP complex and demonstrated by Applicant’s own specification which teaches the formation of the 7-DAFSK-PVP complex with the DAFSK and PVP just present in the solution; and the complex properties (i.e. mass fraction and improved solubility) are also expected to be present as products of identical or substantially identical chemical composition cannot have mutually exclusive properties (i.e. about 24% mass fraction with PVP of MW 2.5kDa, about 8% mass fraction with PVP of MW about 24 kDa, improved solubility up to3x). Applicant’s argument that Majeed does not teach optimizing the PVP is to the reference individually, and one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Majeed teaches the inclusion of PVP wherein optimization of its known molecular weight as established by Rowe to attain the desired therapeutic profile is prima facie obvious with a reasonable expectation of success absent evidence of criticality for the molecular weight values claimed.
In response to applicant's arguments against the Rowe reference individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
With regards to the assertion that Majeed and Rowe cannot be combined as forskolin and its analog cannot be assumed to behave in a similar fashion, this is not persuasive as Majeed expressly teaches the inclusion of 7-DAFSK in the solution with PVP wherein it would naturally form the complex in solution which is also demonstrated by Applicant specification, Rowe is merely presented to establish the known molecular weight for PVP.
Accordingly, the rejection stands.
Conclusion
Claims 1, 3, 9, 11-12, 14-17 are rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GIGI GEORGIANA HUANG whose telephone number is (571)272-9073. The examiner can normally be reached Monday-Thursday 9:00-5:00pm.
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/GIGI G HUANG/Primary Examiner, Art Unit 1613
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