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 .
Status of the Application
This Office Action is in response to applicant’s arguments filed on 8/25/26. Claims 6-7, 11-14, 17-50, 52 have been cancelled. Claims 1-5, 8-10, 15-16, 51 are pending. Claims 1-5, 8-10 have been amended. Claims 1-5, 8-10, 15-16, 51 are examined herein.
The amendments to the claims have rendered all rejections of the last Office Action moot, therefore hereby withdrawn. The following new rejections will now apply.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-5, 8-10, 15-16, 51 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
There is no support for the limitation “memantine” in Applicant’s originally filed disclosure.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1, 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Madden et al. (US Patent Application 2014/0100155) in view of Staunton et al. (WO 2006/119295).
The instant claims are directed to a method for treating cystic fibrosis in a subject in need thereof by administering ivacaftor and memantine.
Madden et al. teach a method of treating cystic fibrosis by administering a combination therapy comprising a CFTR corrector, CFTR potentiator, mucolytic, and an anti-inflammatory agent (abstract). A preferred CFTR potentiator is Kalydeco (ivacaftor) (paragraph 0051). A preferred mucolytic is Dornase alfa (paragraph 0053). Inflammation is taught as a major component of cystic fibrosis. A preferred anti-inflammatory is ibuprofen (paragraph 0054).
However, Madden et al. fail to teach memantine.
Staunton et al. teach that memantine is useful for treating cystic fibrosis (page 32, lines 19-22).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have combined ivacaftor, Dornase alfa, and ibuprofen, as taught by Madden et al., with memantine, as taught by Staunton et al.
A person of ordinary skill in the art would have been motivated to make this combination because each active agent has been individually taught to be useful in the treatment of cystic fibrosis. Therefore, the skilled artisan would have had a reasonable expectation of success in the treatment of cystic fibrosis by the therapeutically additive effect of combining two known active agents for the same purpose.
"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.... The 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).
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Madden et al. (US Patent Application 2014/0100155) in view of Staunton et al. (WO 2006/119295), as applied to claims 1, 3-4, and further in view of Heltshe et al. (“Ivacaftor-treated Patients with Cystic Fibrosis Derive Long-Term Benefit Despite No Short-Term Clinical Improvement,” American Journal of Respiratory and Critical Care Medicine, 2018, Volume 197, Number 11).
The instant claims are directed to a method for treating cystic fibrosis in a subject in need thereof by administering ivacaftor and memantine, wherein the subject is an ivacaftor non-responder.
Madden and Staunton et al. teach as discussed above, however, fail to teach wherein the subject is an ivacaftor non-responder.
Heltshe et al. teach that some ivacaftor-treated patients with cystic fibrosis fail to show an immediate benefit (page 1483, first paragraph). Some ivacaftor-treated patients demonstrate benefit 2 years after initiation. Some patients without short-term benefit may still demonstrate long-term efficacy. There was no statistically significant attenuation in rate of FEV, decline in the 2 years after initiating ivacaftor compared with the 2 years immediately before. Notably, there was no statistically significant difference between the responders and non-responders when comparing PEx rates, BMI change/yr, or FEV decline/yr (page 1485, paragraph bridging left and right columns).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have administered ivacaftor and memantine, as taught by Madden and Staunton et al., to a patient with cystic fibrosis who is an ivacaftor non-responder, as taught by Heltshe et al.
A person of ordinary skill in the art would have been motivated to administer ivacaftor and memantine to cystic fibrosis patient who is an ivacaftor non-responder because it is known that some patients do not respond to ivacaftor early in the treatment, however, eventually demonstrate ivacaftor efficacy. Therefore, the skilled artisan would have had a reasonable expectation of success in the eventual treatment of cystic fibrosis by administering ivacaftor, either immediately or after a short period of time.
Claims 5, 8-10, 15-16, 51 are rejected under 35 U.S.C. 103 as being unpatentable over Madden et al. (US Patent Application 2014/0100155) in view of Cozma (US Patent Application 2019/0128901, of record) and Klavdianou et al. (“Dkk1: A key molecule in joint remodelling and fibrosis,” Mediterr. J. Rheumatol, 2017, 28, 4, 174-182).
The instant claims are directed to a method for treating cystic fibrosis in a subject by detecting a level of biomarker (DKK1) and administering ivacaftor.
Madden et al. teach a method of treating cystic fibrosis by administering a combination therapy comprising a CFTR corrector, CFTR potentiator, mucolytic, and an anti-inflammatory agent (abstract). A preferred CFTR potentiator is Kalydeco (ivacaftor) (paragraph 0051). A preferred mucolytic is Dornase alfa (paragraph 0053). Inflammation is taught as a major component of cystic fibrosis. A preferred anti-inflammatory is ibuprofen (paragraph 0054).
However, Madden et al. fail to disclose DKK1.
Cozma teaches methods for diagnosing cystic fibrosis in a subject, methods for determining the course of cystic fibrosis in a subject, and methods for determining the effectiveness of at least one treatment applied to the subject being positively tested for cystic fibrosis by detecting a biomarker in a blood sample from the subject through mass spectrometric analysis (abstract and paragraph 1). The biomarker may be a protein and a fragment thereof (paragraph 0370). In one embodiment, the level of a biomarker is indicative for the subject for suffering from cystic fibrosis when compared to a control level of the biomarker (paragraph 0393). In another embodiment, a method of determining the effectiveness of a composition for the treatment of cystic fibrosis may include the steps of determining a level of biomarker, administering the therapeutic compound, re-determining the level of the biomarker, comparing the level before and after administering the therapeutic compound to determine the effectiveness of the treatment (paragraph 0417).
Klavdianou et al. teach that DKK-1 is involved in the fibrotic process or fibrosis, therefore serving as a biomarker (abstract).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have detected the level of the biomarker, DKK1, as taught by Cozma and Klavdianou et al., in the method of treating cystic fibrosis, as taught by Madden et al.
A person of ordinary skill in the art would have been motivated to detect the level of DKK1 because Cozma and Klavdianou et al. teach that biomarkers can be used to not only diagnose the severity of cystic fibrosis in a subject, but also determine the level of effectiveness of a treatment, which is a useful tool to decide if the subject is a responder or non-responder to the aforementioned treatment.
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 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 Yong S. Chong whose telephone number is (571)-272-8513. The examiner can normally be reached Monday to Friday: 9 AM to 5 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached at (571)-270-7674. The fax phone number for the organization where this application or proceeding is assigned is (571)-273-8300.
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/Yong S. Chong/Primary Examiner, Art Unit 1623
