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 .
This action is responsive to papers filed 11/04/2024.
Claims 15, 17, and 20 have been amended. Claim 34 has been newly added and no claims have been newly canceled.
Claims 1-2, 4-7, 12-13, 15-17, 20-28, and 34 are currently pending.
Claims 1-2, 4-7, 12-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 11/20/2023.
Claims 15-17, 20-28, and 34 have been examined on their merits.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 15-17, 20-28 and 34 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 15, the preamble is written to include expanding MECs and optionally differentiating the MECs which are in vitro methods and also recites prevent, inhibit or treat a degenerative lung disease or disorder or enhance airway repair in a mammal which are in vivo methods. The body of the claim requires one step for administration to a mammal which is an in vivo method without any in vitro steps for expanding or differentiating MECs. This renders the scope of the claim unclear as the body of the claim does not include steps that the preamble states are occurring.
In addition, it is unclear which cells are being referred to in line 5 of claim 15. Are these cells MECs or are they any cell that has been exposed to the modulators?
Because claims 16-17 and 20-28 and 34 depend from indefinite claim 15 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112, second paragraph.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 15-17, 20-21, 24-28 are rejected under 35 U.S.C. 103 as being unpatentable over Clarke et al (US 2014/0336159) in view of Duan et al (Am. J. Cell Mol. Biol. 1998).
Regarding claims 15-17, 20 and 26, Clarke disclose methods for treating respiratory diseases with calcium ions (page 1 para 4) wherein the diseases treated include COPD, emphysema, and cystic fibrosis (page 3 para 28). Suitable therapeutic agents may be used in the methods described and that may be coadministered including anti-inflammatory agents or therapeutics helpful for chronic maintenance of cystic fibrosis (pages 12-13 para 112). Suitable anti-inflammatory agents and/or agents that modulate inflammatory cytokine/chemokine expression or secretion include modulators of Lef1 (page 13 para 121-122).
Clarke does not describe a specific embodiment for treating a respiratory disease, such as cystic fibrosis, with a modulator of Lef1.
Duan teach that there is a need to develop gene therapy strategies in the treatment of cystic fibrosis (page 750 column 1 to page 751 column 2). Lef1 transcription factor expression defines airway progenitor cell targets for in utero gene therapy of submucosal gland in cystic fibrosis (Title, abstract). Duan demonstrate that in vivo targeting to Lef1 transcription factor within airway progenitor cell populations using recombinant retroviral vectors provides stable transgene expression throughout gland morphogenesis and the foundation for the development of gene therapy strategies in the treatment of cystic fibrosis airways (page 751, column 2, second paragraph). Agents that induce expression of Lef1 are described and include cells exposed ex vivo to an activator of Lef1 (page 755 results to page 756, column 2 first paragraph).
One of ordinary skill in the art would have been motivated to select cystic fibrosis from the list of respiratory diseases in Clarke and a modulator that induces expression of Lef1 from the list of additional therapeutic agents because Duan teach and suggest that there is a need for treatment strategies for cystic fibrosis and that Lef1 modulators that induce expression of Lef1 are useful in the treatment of this respiratory disease. One of ordinary skill in the art would have had a reasonable expectation of success because Clarke indicate that cystic fibrosis is a suitable respiratory disease for treatment with their method and Lef1 is a suitable target for modulation and providing an anti-inflammatory effect.
Regarding claim 21, Clarke teach that subjects can be animals or humans (page 6 para 55).
Regarding claims 24-25, Clarke teach wherein the composition is administered intravenously (systemically) or intra-bronchial by inhalation (bronchoscopically) (page 12 para 109).
Regarding claim 27, While Clarke does not specifically describe using an amount that increases the number of ionocytes and/or enhances airway regeneration, Clarke is directed to treating respiratory diseases by attenuation of severity of acute exacerbations (worsening of symptoms) to reduce airway inflammation and excess airway mucus and airflow limitation (page 3 para 28) which would motivate the person of ordinary skill in the art to select amounts that enhance airway regeneration. One of ordinary skill in the art would have had a reasonable expectation of success because Clarke describe optimizing their therapy in combination with other therapeutic agents (page 1 para 4).
Regarding claim 28, Clarke teach wherein the composition for administration may include therapeutic agents such as lithium (page 10 para 85 and 87) or SB-216763 (page 14 para 126).
Therefore the combined teachings of Clarke et al and Duan et al render obvious Applicant’s invention as claimed.
Claim(s) 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Clarke et al (US 2014/0336159) in view of Duan et al (Am. J. Cell Mol. Biol. 1998) as applied to claims 15-17, 20-21, 24-28 above, and further in view of Cypel et al (WWW. SciencetranslationMedicine.org, 2009).
Regarding claims 22-23, Clarke does not specifically describe combining their treatment with a lung transplant, but they do disclose wherein their calcium-containing compositions increased airway surface lining height in cells obtained from excess tissue from donor lungs and excised recipient lungs that were obtained at the time of lung transplant. These data show that their formulations are effective in increasing ASL height in CF patient lung cells (page 30 Example 2 para 265-270).
Cypel teach that lung transplant is a lifesaving therapy for patients suffering from end-stage lung diseases, such as emphysema and cystic fibrosis. Cypel describe a strategy to preserve lungs with gene therapy (abstract, page 1).
One of ordinary skill in the art would have been motivated to combine the Clarke method of treating cystic fibrosis with Lef1 gene therapy before, during or after a lung transplant because Cypel teach that lung transplant is a lifesaving therapy for patients suffering from end-stage lung diseases, such as emphysema and cystic fibrosis, and that it can be combined with gene therapy to enhance the therapeutic effect. One of ordinary skill in the art would have had a reasonable expectation of success because Clarke teach that their composition was effective when exposed to airway cells obtained during a lung transplant.
In addition, 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 option to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. In re Kerkhoven (MPEP 2144.06).
Therefore the combined teachings of Clarke et al, Duan et al and Cypel et al render obvious Applicant’s invention as claimed.
Claim(s) 34 is rejected under 35 U.S.C. 103 as being unpatentable over Clarke et al (US 2014/0336159) in view of Duan et al (Am. J. Cell Mol. Biol. 1998) and Cypel et al (WWW. SciencetranslationMedicine.org, 2009) as applied to claims 15-17, 20-28 above, and further in view of Nagai et al (Gene Therapy 2014).
Regarding claim 34, Clarke does not specifically describe combining their treatment with valproic acid. However, Clarke do describe optimizing their therapy in combination with other therapeutic agents (page 1 para 4) including gene therapy (page 13 para 122 and page 17 para 149).
Nagai teach that valproic acid is a clinically safe compound that is useful in the treatment of cystic fibrosis, both on its own as a reducer of inflammation and also when used in conjunction with gene therapy as it enhanced vector-mediate gene expression (page 2 second paragraph, page 3).
One of ordinary skill in the art would have been motivated to modify the Clarke method of treating cystic fibrosis with Lef1 modulation to include valproic acid because Nagai teach that valproic acid is a clinically safe compound that is useful in the treatment of cystic fibrosis, both on its own as a reducer of inflammation and also when used in conjunction with gene therapy as it enhanced vector-mediate gene expression (page 2 second paragraph, page 3). One of ordinary skill in the art would have had a reasonable expectation of success because Clarke describe optimizing their therapy in combination with other therapeutic agents, including gene therapy and Nagai indicate that valproic acid has been proven to be clinically safe and useful in the treatment of cystic fibrosis.
In addition, it is prima facie obvious to combine compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third option to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. In re Kerkhoven (MPEP 2144.06).
Therefore, the combined teachings of Clarke et al, Duan et al, Cypel et al and Nagai et al render obvious Applicant’s invention as claimed.
Response to Arguments
Applicant's arguments filed 11/04/2024 have been fully considered but they are not persuasive.
Applicant asserts that their amendments to the claims have rendered the claims definite and comply with 112(b).
This is only found partially persuasive. While the amendments to the claims have removed some of the issues hindering the clarity of the claims they have not addressed all the ambiguities and thus ethe rejection under 35 USC 112(b) remains above.
Applicant has noted that the 103 rejection over Clarke was directed to US 2014/0336159 rather than WO 2014/0336159 due to a typographical error. The Examiner appreciates this notation and the correction has been made.
Applicant argues that one of ordinary skill in the art would not be motivated to combine Clarke and Duan because Clarke is directed to treating respiratory tract with calcium salts while Duan is directed to in utero gene therapy and thus they are not combinable.
This is not found persuasive. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
The combination of Clarke and Duan in the rejection of claim 15 does not rely on the bodily incorporation of the two methods, but on a motivation to select cystic fibrosis and LEF1 from the lists recited in the disclosure of Clarke. Clarke specifically recites cystic fibrosis as a lung disease treated by their method and LEF1 modulation as an option for use in their method as well. Duan provides additional motivation to select those options for combination in a method to treat a lung disease such as cystic fibrosis with LEF1 as suggested by Clarke.
Applicant argues that there is no reasonable expectation of success for combining Clarke and Duan because Duan states there are significant obstacles for gene therapy due to it inaccessibility from the lumen of adult proximal airways and suggests in utero gene therapy as an attractive alternative strategy (abstract of Duan).
This is not found persuasive. First, the combination of Clarke and Duan in the rejection of claim 15 does not rely on the bodily incorporation of the two methods, but on a motivation to select cystic fibrosis and LEF1 from the lists recited in the disclosure of Clarke. Clarke specifically recites cystic fibrosis as a lung disease treated by their method and LEF1 modulation as an option for use in their method as well. Second, while Duan is presenting in utero gene therapy as a potential alternative to gene therapy in adults, the use of gene therapy in general for the treatment of cystic fibrosis is well known in the prior art as evidenced by the Cypel and Nagai references cited above.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Bayramov et al., "Novel Functions of Noggin proteins: inhibition of Activin/Nodal and Wnt signaling", Development, 2011, Vol. 138, No. 24, pp. 5345-5356.
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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA J SCHUBERG whose telephone number is (571)272-3347. The examiner can normally be reached 8:30-5:00 EST.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631