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 . 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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9 July, 2025 has been entered.
Election/Restrictions
Applicants elected group I (methods of treatment) and the treatment of idiopathic pulmonary fibrosis with SEQ ID 1 attached to an Fc domain without traverse in the reply filed on 26 March, 2024.
Claims Status
Claims 1, 2, 4, 5, 7-11, 17, 20-22, 28-30, 39, 40, and 42-44 are pending.
Claim 1 has been amended.
Claim 44 is new.
Claims 7-11, 20, 22, 28, 30, and 42 have been withdrawn due to an election/restriction requirement.
Withdrawn Rejections
The rejection of claims 1, 2, 4, 17, 21, 39, 40, and 43 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph due to lack of enablement for treating appropriate inflammation is hereby withdrawn due to amendment.
The rejection of claims 1-5, 17, 21, 29, 39, 40, and 43 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph for the addition of new matter is hereby withdrawn due to amendment.
The rejection of claims 1-5, 17, 21, 29, 39, 40, and 43 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph due to uncertainty as to what undesirable inflammation constitutes is hereby withdrawn due to amendment.
Maintained/Modified Rejections
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.
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.
first rejection
Claim(s) 1, 2, 4, 5, 21, 29, 39, 40, and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Noguchi et al (Resp. Res. (2014) 15(92)) in view of Yoshida et al (Eur. Respir. J. (1997) 10 p2051-2054), Nishimatsu et al (PLOS One (2015) 10(7) e0133874), and Bogden et al (US 5,736,517, cited by applicants). Please note that this rejection does not read on applicant’s elected species.
Noguchi et al look at the effect of nitric acid on pulmonary fibrosis in mice (title). Knockout mice without the ability to generate NO were significantly impaired compared to WT mice in a model of idiopathic pulmonary fibrosis (9th page, 2nd paragraph). Treatment with an NO donor significantly prevented the progression of the disorder and the buildup of collagen (4th page, 2nd paragraph).
The difference between this reference and the examined claims is that this reference does not discuss NMB therapy.
The teachings of Noguchi et al are supported by Yoshida et al. Low concentrations of NO improved hemodynamic values in IPF, and improved oxygenation when administered with oxygen compared to controls without NO administration (p2053, 1st column, 2nd paragraph). This reference discusses the advantages of administration of low amounts of NO to IFP patients.
Nishimatsu et al discuss treatment of erectile dysfunction using NMB (title). Diabetic mice were administered an adenovirus encoding the protein (3d page, 4th paragraph), which restored erectile function lost due to the diabetes (5th page, 4th paragraph). One effect of this treatment was to increase or protect nNOS levels (11th page, 1st paragraph) and eNOS levels (11th page, 2nd paragraph), and was proposed to work by angiogenesis induced by nNOS and eNOS, and possibly by reducing apoptosis (14th page, 1st paragraph). This reference shows that NMB can increase NO production levels.
Bogden et al discuss treatment of cancer with peptides (title). Among the peptides used is NMB (abstract). This reference shows that peptides can be used as an alternative to the adenovirus therapy of Nishimatsu et al.
Therefore, it would be obvious to treat IFP patients with NMB, as Nishimatsu et al show that this compound increases NO synthesis, which both Noguchi et al and Yoshida et al show can benefit patients with this disorder. As those two references show the advantages of NO applied by three different methods (direct inhaled, produced by the patient, and NO donor), an artisan in this field would attempt this therapy with a reasonable expectation of success.
Furthermore, it would be obvious to use the peptide of Bogden et al, as a simple substitution of one known element (the adenovirus of Nishimatsu et al) with another (the peptide of Bogden et al) yielding expected results (location of the peptide in the patient). As the adenovirus of Nishimatsu et al generates the peptide, an artisan in this field would attempt this therapy with a reasonable expectation of success.
Bothh Noguchi et al and Yoshida et al discuss idiopathic pulmonary fibrosis, and Nishimatsu et al renders obvious treating it with NMB, rendering obvious claims 1, 2, 4, 5 and 29.
This is the same therapy, so it will necessarily have the same effects, rendering obvious claims 21, 39, 40, and 44.
response to applicant’s arguments
Applicants argue that Noguchi et al discusses prevention of damage by bleomycin rather than treatment of pulmonary fibrosis, that Yoshida et al discusses treatment of hypertension rather than pulmonary fibrosis, and that a person of skill in the art would assume that increasing NO levels would be detrimental.
Applicant's arguments filed 9 July, 2025 have been fully considered but they are not persuasive.
Applicants argue that Noguchi et al is discussing prevention of bleomycin damage rather than treatment if pulmonary fibrosis. In other words, the argument is that the therapy prevents the initial insult from progressing to idiopathic pulmonary fibrosis. But, by definition, the initial insult in idiopathic pulmonary fibrosis is unknown (otherwise, it would not be idiopathic). There is no reason to believe that the insult is not continuing; in which case, the therapy of Noguchi et al is relevant.
Applicants argue that Yoshida et al discusses treatment of hypertension. However, this is a feature of idiopathic pulmonary fibrosis, and the reference clearly states that the patients have that disorder. Note that this seems to be well understood, with multiple researchers verifying it, note Hajian et al (Int. J. COPD (2016) 11 p1533-1541, p1540, 1st column, 2nd paragraph, for example).
Finally, applicants argue that a person of skill in the art would assume that increasing NO levels would not be beneficial. Most of the references are discussing correlation, rather than working out the etiology. In addition, NO levels in pulmonary fibrosis vary considerably, note Guilleminault et al (Resp. Med. (2013) 107 p1789-1796, abstract). Given that there are multiple references of record stating or suggesting that NO will provide a benefit in pulmonary fibrosis, this is not sufficient to overcome the rejection.
second rejection
Claim(s) 1, 2, 4, 5, 17, 21, 29, 39, 40, 43, and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Noguchi et al (Resp. Res. (2014) 15(92)) in view of Yoshida et al (Eur. Respir. J. (1997) 10 p2051-2054), Nishimatsu et al (PLOS One (2015) 10(7) e0133874), Bogden et al (US 5,736,517, cited by applicants), Le Tourneau et al (J. Natl. Cancer Inst. (2009) 101 p708-720), and Lim et al (US 20170128589).
As noted above, Noguchi et al, Yoshida et al, Nishimatsu et al, and Bogden et al render obvious claims 1, 2, 4, 5, 8, 9, 21, 29, 39, and 40.
The difference between the combination of these references and the remaining claims is that the combination does not give a dosing schedule, nor does it mention adding an Fc domain to the polypeptide.
Le Tourneau et al discuss dose escalation for phase I clinical trials (title). The main goal of these studies is to find the dose and dose schedule of new drugs or drug combinations for subsequent trials (abstract). A number of different ways of performing this optimization are discussed (fig 2, p711, top of page). This reference discusses how to optimize the dose schedule for a drug.
Kim et al discuss improving solubility of a polypeptide by attaching an Fc domain (title). This can make formulation of the drugs simpler (paragraph 7). This reference discusses addition of antibody Fc domains to polypeptides.
Therefore, it would be obvious to optimize the dose and dose schedule of the drug, as described by Le Tourneau et al. The MPEP states that “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or working ranges by routine experimentation" In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) (MPEP2144.05.II). As every drug used has had the dose and dose schedule optimized, an artisan in this field would attempt this process with a reasonable expectation of success.
Furthermore, it would be obvious to attach an antibody Fc domain to the peptide of Bogden et al, to increase its solubility and make it easier to formulate. As Lim is generic as to the polypeptide, an artisan in this field would attempt this process with a reasonable expectation of success.
Le Tourneau et al discuss optimizing the dose schedule, which includes multidose scenarios. Thus, the combination of references renders obvious claim 17.
Lim et al renders obvious attaching an antibody Fc domain, rendering obvious claim 43.
response to applicant’s arguments
Applicants have presented the same arguments for both rejections under this statute, which were answered above.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658