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 .
Applicants response filed on 02/03/26 is acknowledged as are the claim amendments. Claims 1 and 3-20 are pending with claims 13-20 withdrawn and claims 1 and 3-12 rejected.
Maintained REJECTIONS
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that
form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 and 3-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over US 2011/0218143 (‘143) as evidenced by Triptolide (2017).
‘143 claims the pharmaceutical composition which is an effective amount
triptolide, a Tryptigerium derivative, celasterol, functional and structural analogs, and
combinations thereof (claims 16-17). ‘143 teaches that various methods of extraction for
Tryptigerium wolfordii are taught US 4,005,108 which is incorporated in its entirety and
actives such as triptolide can be used individually or together [0099].
‘143 teaches triptolide [0243, 0246] and various known derivatives include
dihydroagarofurans [0243-0244] (instant E), 77 demethylzeylasteral (instant H) [0258, 0261], etc. amongst others. Example 14 teaches that Tripteryguim wilfordii is a known woody vine native to eastern and Southern China, Korea, Japan and Taiwan with other 380 secondary metabolites of which 95% are terpenoids including triptolide which can be used alone or in various combinations with each other with effective medicinal chemistry [0238]. ‘143 also teaches that such agents are included in amounts of 50, 100, 500 etc µg/kg [0150 and 0264]. ‘143 teaches that the active triptolide and analogs thereof can be included in amounts of 1-1000 µg/kg or in some embodiments 1mg, 2mg, etc. per day and other derivatives in amounts of 0.001-300 mg/kg, etc. [0101-0105]. Thus ratios are also envisaged from the above. Example 5 provides Triptolide in combination with celastrol in amounts that are overlapping.
Since the density of triptolide is ~1.48g/cm3 (as evidenced by Table in Triptolide
2017) then ~1000 µg/kg is = 1.48 µg/mL which is within the instant claimed range.
Example 1 administers triptolide to a patient at 400 µg/kg (which is = 0.592 µg/mL)
which is again within the instant claimed range; whereas other examples provided
2.5mg/kg, and 50, 100, 500 etc µg/kg of derivatives [0202, 0264].
In the event that the combination of 2 or more of G with any one of E, H, I J or P is not taught with sufficient specificity then it is obvious in light of the teaching of ‘143 and the
embodiments disclosed therein, which clearly disclose triptolide in combination with one
or more of additional derivatives and functional and structural analogs which clearly
include G, H and others as instant claimed.
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 of this title, 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 and 3-12 are rejected under 35 U.S.C. 103 as being unpatentable over
Brinker et al.in view of US 2011/0218143 (‘143) ) as evidenced by Triptolide (2017).
Brinker et al teaches plants such as Tryptigerium wolfordii have a long traditional
Chinese medicinal history and through the years a lot of interest has been placed on triptolide to treat various conditions and over 300 other compounds have been identified
from Tryptigerium genus (abstract; Fig 1: Triptolide ) and Section 4.2 teaches that
various compounds such as triptolide are known to treat cancer (p738-739). Additionally
Brinker et al disclose that various other compounds of Tryptigerium have important
cancer fighting activity including the dihydroagarofurans (p. 740; Fig 5) with
demethylzeylasteral (77) and also triptohypol (80) taught as well (p. 749; Fig 22).
Brinker et al does not teach the specific amounts or the specific combination of
the various extract components together but suggests such investigations.
‘143 is taught above and teaches that various methods of extraction for
Tryptigerium wolfordii are taught US 4,005,108 which is incorporated in its entirety and
actives such as triptolide can be used individually or together [0099].
‘143 teaches triptolide [0243, 0246] and various known derivatives include
dihydroagarofurans [0243-0244] (instant E), 77 demethylzeylasteral (instant H) [0258, 0261], etc. amongst others. Example 14 teaches that Tripteryguim wilfordii is a known woody vine native to eastern and Southern China, Korea, Japan and Taiwan with other 380 secondary metabolites of which 95% are terpenoids including triptolide which can be used alone or in various combinations with each other with effective medicinal chemistry [0238]. ‘143 also teaches that such agents are included in amounts of 50, 100, 500 etc µg/kg [0150 and 0264]. ‘143 teaches that the active triptolide and analogs thereof can be included in amounts of 1-1000 µg/kg or in some embodiments 1mg, 2mg, etc. per day and other derivatives in amounts of 0.001-300 mg/kg, etc. [0101-0105]. Thus ratios are also envisaged from the above. Example 5 provides Triptolide in combination with another derivative of the plant in amounts that are overlapping.
Since the density of triptolide is ~1.48g/cm3 (as evidenced by Table in Triptolide
2017) then ~1000 µg/kg is = 1.48 µg/mL which is within the instant claimed range.
Example 1 administers triptolide to a patient at 400 µg/kg (which is = 0.592 µg/mL)
which is again within the instant claimed range; whereas other examples provided
2.5mg/kg, and 50, 100, 500 etc µg/kg of derivatives [0202, 0264].
It would be obvious to an ordinary person at the time of filing to combine Brinker
et al with ‘143. The combination of a known means of fighting cancer and various other
diseases with the Tryptigerium wolfordii including triptolide and demethylzeylasteral of
Brinker et al with the dosing and administration together of the various extracts of ‘143
is within the purview of the skilled artisan and would yield predictable results. The
combination of known extract components with the known method of dosing and
administering them together in a subject would be obvious under MPEP KSR 2141: “(C)
Use of known technique to improve similar devices (methods, or products) in the same
way”.
Response to arguments
Applicant’s argue that there is not specific synergistic combination ‘for inhibiting a drug-resistant cancer’ as instant claimed. Applicants argue that Kaushal teaches a laundry list of derivatives but not specific combinations as now instant claimed for treatment of cancer. The examiner respectfully points out that the claims do not claim synergism nor are the claims directed to methods of treating/inhibiting but are rather directed to a composition with triptolide and another derivative of tripteryguim wilfordii such as amended to compound E, H, I, J or P. As the claims are directed to a composition any future intended use such as ‘for inhibiting drug-resistant cancer’ are not considered rather what is considered is: is it known in the art to mix together triptolide with another derivative of tripteryguim wilfordii in a composition and are amounts as claimed also known and the answer is yes. The prior art teaches combinations of triptolide with other known tripteryguim wilfordii derivatives; specifically the derivatives of dihydroagarofurans [0243-0244] (instant E), 77 demethylzeylasteral (instant H) ) [0258, 0261], etc. amongst others are disclosed in ‘143. Further various amounts and ranges are also disclosed as laid out above.
If applicant is arguing synergism then the claims need to be commensurate in scope with any data presented and they are not at present. Further the argument about ‘tissue repair’ or ‘regeneration’ of ‘143 is moot since these are composition claims. Should applicant wish to pursue method of treatment/inhibiting claims in a CON or DIV then applicant is encouraged to do so. Applicants arguments about the data in Tables 3 and 5 is not persuasive either since these relate to very narrow amounts and do not compare to other known derivatives in the art, but rather only show the 5 now instant claimed again in very specific amounts and ratios and only on ‘cells’ again which is not commensurate in scope with the composition claims presented. Again claim 1 required no amounts or ratios or other carriers/solvents.
Further with regards to Brinker in view of ‘143 applicants argue there is no prima facie case of obviousness and no motivation to combine them, and the examiner respectfully points out that applicant's argue against the references 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).
It should be noted that the motivation to combine references can be different from the ones set forth by Applicant. That is, as long as motivation exists to combine the elements, the problem to be solved does not have to involve the same reason for treatment of drug resistant cancer with a composition. As such, the examiner respectfully submits that there is motivation to combine the teachings of Brinker in view of ‘143 and the expected result of a mixture of various dervatives of tripteryguim wilfordii derivatives; specifically the derivatives of dihydroagarofurans [0243-0244] (instant E), 77 demethylzeylasteral (instant H) in combination with triptolide which is already known to treat cancer as is tripteryguim wilfordii derivatives; specifically the derivatives of dihydroagarofurans (instant E), 77 demethylzeylasteral (instant H) according to Brinker and the combination of 2 known compounds to make a 3rd known composition for the same purpose is obvious.
Applicants argue that they have unexpected data and synergetic effect and point to tables 3 and 5, the issue with this is these are provided in specific amounts (microgram/ml) and in specific ratios to one another as well and the instant claims do not require that, in fact claim 1 doesn’t require any amount at all so is 1 mole able to treat drug resistant cancer? What ratios and combinations in which carriers and additives are able to produce synergism? Does one drop? Again the claims are broadly drawn to a composition and not a method and the burden is on applicant to establish that the composition is not anticipated and not obvious over the prior art which teaches mixtures of various derivatives of tripteryguim wilfordii derivatives; specifically the derivatives of dihydroagarofurans [0243-0244] (instant E), 77 demethylzeylasteral (instant H) with Compound G. Further, Applicants claims are not commensurate with the data presented. Further the arguments drawn to compound P synergism are immaterial since the prior art clearly teaches triptolide, diagrofurans, and demethyzeylasteral are benefical and applicants claims are not drawn to the combination of G and P alone in the specific amount as shown.
Conclusions
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the
examiner should be directed to BETHANY BARHAM whose telephone number is
(571)272-6175. The examiner can normally be reached on M-F 9:30AM-6pm. Information regarding the status of an application may be obtained from the
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Status information for unpublished applications is available through Private PAIR only.
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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
Prosecution Insights