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 .
Acknowledgment of Papers Received: Amendment/Response dated 4/9/26.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-37 is/are rejected under 35 U.S.C. 103 as being unpatentable over the combined disclosures of Hughes et al (US 2008/0261984 hereafter Hughes) in view of Faure et al (US 9,161,917 hereafter Faure).
Hughes discloses a pharmaceutical composition comprising a uniform blend of reboxetine as the sole active agent (abstract, Example), meeting the initial limitations of claim 1. The composition comprises excipients including microcrystalline cellulose, calcium phosphate, especially dibasic calcium phosphate dihydrate, hydroxypropyl methylcellulose, crospovidone and combinations thereof [0045- 0047], meeting the limitations of claims 2-15, 26-2 and 30-34. The silicon dioxide can be present from 0.2-1% [0048], meeting the limitations of claims 36. The magnesium stearate can be present from 0.5-3 % [0049], meeting the limitations of claim 37. The reboxetine can be free or present as a salt pharmaceutical acceptable salt of the reboxetine is mesylate [0036, claims] meeting the limitations of claims 21 and 23. The reboxetine can be from 0.1-10 mg, preferably 4-6 mg [0073, 0114-0115], meeting the limitations of claim 23, 24, 25 and 29.
Regarding the specific concentrations and ranges of claims 16-20, Hughes while not explicitly disclosing these exact compounds in these exact ranges, the disclosures of the prior art would render the claims obvious. The reference discloses a range of excipients including binders, diluents, disintegrants and lubricants [0046-0051]. The reference does not disclose the specific ranges for each excipients listed such as the microcrystalline cellulose, hypromellose, calcium phosphate, but these compounds fit in the categories of well establish excipients which are discloses for specific ranges. The binders are present from 10-90%, the diluent up to 85%, the disintegrant is present from 2-10% and the lubricant is present from 0.25 to 10% [0051]. The general conditions of the claims have been met in that the components are disclosed and the categories of the formulation are disclosed in general ranges. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See In re Aller, 220 F.2d 454 105 USPQ 233, 235 (CCPA 1955).
Regarding the presence and concentration of less than 13 ppm of compound
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, it is the position of the Examiner that since Hughes is silent to and does not disclose the presence of this compound and that 0 ppm is “less than 13 ppm” the disclosures of Hughes will be sufficient to meet this limitation of claim 1 and 22. The claims are written with no lower limit, meaning 0 would be the implied limit and as such, 0 ppm of the compound, given the broadest reasonable interpretation of the claim, would read on the claim limitation. Thus., Hughes discloses 0 ppm of the compound and thus, Hughes meets the limitation of the claims.
While the prior art discloses a pharmaceutical composition comprising a uniform blend of reboxetine and pharmaceutically acceptable excipients, the reference is silent to the random testing of a single batch and content of the samples. However such testing is well known in the prior art for quality control, especially in uniform formulation comprising an active agent and excipients as seen in the Faure patent.
Faure discloses a pharmaceutical formulation comprising a uniform, homogenous blend of excipients including hydroxypropyl methylcellulose (col. 4, lin. 15-25, Examples). The formulation may further comprise reboxetine (col. 9, lin. 25-30). The homogenous blend is formed into tablets baches of 400 mg tablet and 700 mg tablet. 30 tablets from each batch are tested where the %relative standard deviation for the 400 mg tablets of the active agents is 4.96% and the % standard deviation for the 700 mg batch is 3.87% (col. 24, lin. 20-42). This establishes the level of skill in the art regarding quality control and batch testing for consistency of the materials within formulations. It would have been obvious to randomly test the formulation of Hughes in the manner found in Faure in order to ensure consistency in the dosage of the formulation.
With these aspects in mind it would have been obvious to follow the disclosures of the Hughes formulation in order to treat pain. Further it would have been obvious to check for consistency in the formulation as seen in Faure to ensure consistency in the dosage form during production. One of ordinary skill in the art would have been motivated to combine the prior art with an expected result of stable and consistently mass produced pharmaceutical dosage form with measurable and predictable results. It would have been obvious to optimize the formulation of the Hughes patent in order to produce a stable pain reducing formulation and treatment method useful in the treatment of pain.
Response to Arguments
Applicant's arguments filed 4/9/26 have been fully considered but they are not persuasive. Applicant argues that: 1) the amended claims now include a compound that is not disclosed by the prior art combination and that: 2) the prior art combination does not render the claims obvious since the Faure does not teach or disclose batch testing compatible with the Hughes as it only test of Vitamin E and not the active agent.
Regarding 1), as discussed above, the newly amended claim is written without a lower limit, merely that the compound is present in “less than 13 ppm”. As such the lower limit of this range is 0, such that 0 ppm would meet the limitation of the claim. Hughes does not disclose the presence of such a compound or more specifically discloses 0 ppm of the compound, and as such tis would meet the lower limit implied by the claims as they are written. Hughes discloses a pharmaceutical compound comprising a uniform blend of reboxetine, or a salt and a series of excipients. Hughes meets these limitations.
Regarding 2), the combination continues to render the claims obvious regarding the uniformity of the blend. Applicant argues that Faure does not test the uniformity of the active agent, only an excipients which is Vitamin E. Faure is concerned with testing the uniformity of liquid components that are absorbed onto dry components and their uniform distribution. This would be relevant to Hughes, in that various pharmaceutical compositions are disclosed by Hughes, some with liquid reboxetine such as emulsions and solutions. It would be within the interests of an artisan of ordinary skill to verify that the dissolved reboxetine was uniformly distributed in the liquid dosage forms such as creams ointments, lotions, solutions, emulsion and the like. Whether the component being tracked is the active components or the excipients Faure provides methods of checking the uniformity of the liquid components, of which Hughes described multiple embodiments where the reboxetine would be in liquid form and these methods would be useful. As such, the claims remain rejected as it would have been obvious to verify the components as seen in Faure.
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 MICAH PAUL YOUNG whose telephone number is (571)272-0608. The examiner can normally be reached Monday through Friday, 9:00 am to 5:30 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached at 5712720616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICAH PAUL YOUNG/Primary Examiner, Art Unit 1618
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