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
Applicant's election without traverse of the species, ivacaftor (CFTR modulator), memantine (CFTR modulator therapy optimizing agent), and DKK1 (biomarker), in the reply filed 3/12/26 is acknowledged.
Upon further consideration, the species requirement regarding the CFTR modulator therapy optimizing agent and biomarker are hereby withdrawn.
Claims 1-11, 15-16, 26-28, 50-52 are pending. Claims 26-28 have been withdrawn from further consideration as being drawn to a non-elected species. Claims 1-11, 15-16, 50-52 are examined herein insofar as they read on the elected invention and species.
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, 3-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gallardo-Godoy (WO 2009/038913, of record).
Gallardo-Godoy teaches methods for treating cystic fibrosis in a patient by administering compounds and compositions that modulate cystic fibrosis transmembrane conductance regulator (CFTR) (paragraphs 002, 022, 154). These methods increase the amount of CFTR present at the cell surface, thereby inducing a hitherto absent CFTR activity in a patient or augmenting the existing level of residual CFTR activity in a patient (paragraph 0156). In one embodiment, additional therapeutic agents may be selected from a mucolytic agent, an anti-inflammatory agent, or a CFTR modulator other than a compound of the present invention (paragraph 0173). It is noted that the instant specification lists an anti-inflammatory agent as a CFTR modulator therapy optimizing agent (paragraph 0044). Combination therapy is taught where compounds and compositions can be administered concurrently with, prior to, or subsequent to, one or more other desired therapeutics or medical procedures (paragraph 0172).
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 2, 5-6, 8-9, 11, 15, 50-51 are rejected under 35 U.S.C. 103 as being unpatentable over Gallardo-Godoy (WO 2009/038913, of record), as applied to claims 1, 3-4, in view of Cozma (US Patent Application 2019/0128901, of record) and Pollard et al. (US Patent Application 2006/0292562, of record).
The instant claims are directed to a method for treating cystic fibrosis in a subject by detecting a level of biomarker and administering a CFTR modulator therapy.
Gallardo-Godoy teaches as discussed above, however, fail to disclose the claimed biomarker.
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).
Pollard et al. teach that Frizzled is a protein biomarker for cystic fibrosis (paragraphs 0013, 0050, 0085).
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, Frizzled, as taught by Cozma and Pollard et al., in the method of treating cystic fibrosis, as taught by Gallardo-Godoy.
A person of ordinary skill in the art would have been motivated to detect the level of Fizzled because Cozma and Pollard 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.
Claims 7, 10, 16, 52 are rejected under 35 U.S.C. 103 as being unpatentable over Gallardo-Godoy (WO 2009/038913, of record) in view of Cozma (US Patent Application 2019/0128901, of record) and Pollard et al. (US Patent Application 2006/0292562, of record), as applied to claims 1-6, 8-9, 11, 15, 50-51, and further in view of Madden et al. (US Patent Application 2014/0100155) and Reilly et al. (“Targeting the PI3K/Akt/mTOR signaling pathway in Cystic Fibrosis,” 2017, Scientific Reports, 7, 7642, 1-13).
The instant claims are directed to a method for treating cystic fibrosis in a subject by detecting a level of biomarker and administering a CFTR modulator therapy.
Gallardo-Godoy, Cozma, and Pollard teach as discussed above, however, fail to disclose Kalydeco (ivacaftor), ibuprofen, Dornase alfa, and an agent from Tables 1-3.
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).
Reilly et al. teach that targeting the PI3K/Akt/mTOR complex improves CFTR stability and function, specifically inhibition of mTORC1 or MTORC2 complexes would improve CFTR stability or export. A small increase in CFTR expression was observed after treatment with AZD-8055 (page 6, first and second full paragraphs).
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, ibuprofen, and AZD-8055, as taught by Madden and Reilly et al., with a composition comprising a compound that modulates CFTR in the method of treating cystic fibrosis, as taught by Gallardo-Godoy, Cozma, and Pollard.
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).
Similarly, it would also 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 substituted ivacaftor, Dornase alfa, ibuprofen, and AZD-8055, as taught by Madden and Reilly et al., for the mucolytic agent, an anti-inflammatory agent, and CFTR modulator in the method of treating cystic fibrosis, as taught by Gallardo-Godoy, Cozma, and Pollard.
A person of ordinary skill in the art would have been motivated to make these substitutions because of the functional equivalency of each active agent, for example for one mucolytic agent for another. Therefore, the skilled artisan would have had a reasonable expectation of success in the treatment of cystic fibrosis by substituting ivacaftor, Dornase alfa, ibuprofen, and AZD-8055.
Conclusion
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
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