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.
Claims 1-11 are pending and under examination.
Response to Amendment
The amendments and remarks filed 15 December 2025 have been received and entered in full. Claims 1-11 are pending and under examination.
Withdrawn Rejections
The scope of enablement rejection of claims 1-11 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph is withdrawn in response to the deletion of “or prophylactically treating” from independent claim 1.
Maintained Rejections
Note that the prior art rejections set forth below have been modified to account for the limitations of the amended claims.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3 and 10 stand rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Schrattenholz (US 2014/0243269 A1; PTO-892, 10/02/2025).
Schrattenholz teaches and claims a method of treating multiple sclerosis comprising administering to an individual in need of such treatment an effective amount of Nrg-1β1. See, e.g., [0019] and Schrattenholz’s claim 1. Note that a particularly preferred amount of Nrg-1β1 to be administered in Schrattenholz is 600 ng per kg body weight. See [0026], wherein the dosage is taught as one endpoint of a preferred range. This specific dosage is taught as therapeutically effective by this application’s specification. See Example 2. Although Schrattenholz does not explicitly recognize that the administration of the effective amount of Nrg-1β1 fosters a phenotype shift in CD11b+ microglia and macrophages from pro-inflammatory towards an anti-inflammatory phenotype, such would be inherently induced by Schrattenholz’s administering Nrg-1β1, as chemical compounds and their properties are inseparable (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA1963)), as are their processes and yields (In re Von Schickh, 362 F.2d 821, 150 USPQ 300 (CCPA 1966)). Therefore, claim 1 is anticipated.
Similarly, the limitations of claim 3 would be inherently induced by Schrattenholz’s administering Nrg-1β1. Thus, absent evidence to the contrary, Schrattenholz inherently teaches that the effective amount of Nrg-1β1 restores reduced levels of Nrg-1 in the blood and/or in the CNS. Note that Schrattenholz teaches that Nrg-1β isoforms are actively transported through the blood brain barrier and that the excellent bioavailability of Nrg-1β in the brain after intravenous/intraperitoneal injection, is shown in their Examples. See [0032]. This is considered further evidence that claims 1 and 3 are anticipated. Claim 10 is anticipated because Schrattenholz teaches that the Nrg-1β1 can be co-administered with a second medicament for treating MS. See [0029].
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.
Claims 2 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Schrattenholz (US 2014/0243269 A1).
Schrattenholz teaches as set forth above but fails to explicitly teach treating MS wherein the Nrg-1β1 is administered on a dosage regimen or schedule. Schrattenholz also fails to explicitly teach “30” µg/kg body weight.
However, daily administration of Nrg-1β1 is disclosed throughout the Examples in Schrattenholz, as in claim 2. Schrattenholz teaches several preferred dosage ranges of Nrg-1β1, i.e., including 3 to 600 ng/kg body weight and up to 500 µg/kg body weight, as in claim 9.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was effectively filed to arrive at the claimed invention from the disclosure of Schrattenholz. The artisan would have been motivated to make and use the invention as claimed because Schrattenholz teaches daily administration of other conditions throughout the Examples. Furthermore, as stated in MPEP § 2144.05, in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In reWertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In reWoodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). The dosage of claim 9 lies inside the prior art’s preferred dosage ranges. Accordingly, claims 2 and 9 are rendered obvious by Schrattenholz’s teachings. The artisan would have had a reasonable expectation of success based on the cumulative disclosure of this prior art reference.
Claims 4 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Schrattenholz (US 2014/0243269 A1) as applied to claims 1 and 10 above, and further in view of Johnson et al. (Neurology. 1998 Mar;50(3):701-8; PTO-892, 10/02/2025).
Schrattenholz teaches as set forth above but fails to teach the individual of claim 4 or the second medicament of claim 11.
Johnson teaches a method of treating relapsing-remitting MS comprising administration of glatiramer acetate including in individuals that have been diagnosed with MS but are in remission, as in claims 4 and 11. See, e.g., para. spanning pp. 702-703 – section entitled “MS relapse rates”.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was effectively filed to arrive at the combined therapy of Nrg-1β1 and glatiramer acetate for the treatment MS, including in individuals that have been diagnosed with MS but are in remission, as in claims 4 and 11. As recognized in the prior art, each of the agents is taught to be effective for the treatment of MS, and thus the artisan would have both been motivated to combine the agents and have a reasonable expectation that the administered combination would be beneficial for the treatment of the disease. As stated in MPEP § 2144.06, combining equivalents known for the same purpose is prima facie obvious: "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 .... [T]he 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) (citations omitted). Further motivation can be found in Schrattenholz's express teaching to add additional active agents and in Johnson’s teachings that glatiramer acetate decreased and even eliminated relapse in relapsing-remitting MS individuals. See especially p. 703, second para. under section “MS relapse rates”. Accordingly, the cumulative reference teachings render obvious the claimed method and support a reasonable expectation of success.
Claims 4, 6-8 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Schrattenholz (US 2014/0243269 A1) as applied to claims 1 and 10 above, further in view of Masuoka et al. (US 2003/0082138 A1; PTO-892, 10/02/2025).
Schrattenholz teaches as set forth above but fails to explicitly teach treating early stage MS, as in claim 4 or treating individuals who have a level of Nrg-1β1 that is below a threshold level, as in claims 6-8, and again fails to teach the second medicament of claim 11.
Masuoka teaches methods for treating individuals with MS and clinically isolated syndrome (CIS) comprising administering a therapeutically effective amount of interferon β1. See, e.g., abstract. Note that CIS is considered early stage multiple sclerosis. See this application’s specification at p. 1, lines 13-16. Therefore, Masuoka teaches treating early stage MS with interferon β1, as in claims 4 and 11.
It would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was effectively filed to arrive at the combined therapy of Nrg-1β1 and interferon β1 for the treatment MS, including in early stage MS. As recognized in the prior art, each of the agents is taught to be effective for the treatment of MS, and thus the artisan would have both been motivated to combine the agents and have a reasonable expectation that the administered combination of agents would be beneficial for the treatment of the disease. As stated in MPEP § 2144.06, combining equivalents known for the same purpose is prima facie obvious. Further motivation can be found in Schrattenholz's express teaching to add additional active agents. Accordingly, the cumulative reference teachings render obvious the claimed method and support a reasonable expectation of success.
Note that the combination of Schrattenholz and Masuoka meets the limitations of claims 6-8 even though these limitations are not expressly taught by the references. The specification of this application teaches that CIS individuals show a significant reduction (greater than 50% reduction) in Nrg-1β1 levels when compared to healthy individuals. See p. 31, lines 9-18. Thus, absent evidence to the contrary, since the combination of Schrattenholz and Masuoka teaches treating CIS patients, the combination also treating individuals who have a level of Nrg-1β1 about 50% of that of a corresponding healthy individual, as required by claims 6-8.
Response to Arguments
Applicant's arguments filed 15 December 2025 have been fully considered but they are not persuasive. Applicant asserts that Schrattenholz is a broad, speculative document that provides a "laundry list" of dozens of neurological conditions, including MS, for which Nrg-1β1 might serve as a general neuroprotective agent. Applicant asserts that Schrattenholz provides no data for MS, does not identify any Nrg-1β1 deficiency in MS, and fails to teach the specific immunomodulatory mechanism of action discovered and recited in the amended claims.
Schrattenholz specifically claims treatment of MS via administration of Nrg-1β1 in claim 1. MS is only listed along with 9 other diseases in claim 1 and is thus specifically disclosed such that one of ordinary skill in the art would immediately envisage that MS should be treated with Nrg-1β1. As stated in MPEP 2131.02 - "A REFERENCE THAT CLEARLY NAMES THE CLAIMED SPECIES ANTICIPATES THE CLAIM NO MATTER HOW MANY OTHER SPECIES ARE NAMED: …when the species is clearly named, the species claim is anticipated no matter how many other species are additionally named. Ex parteA, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990) (The claimed compound was named in a reference which also disclosed 45 other compounds. The Board held that the comprehensiveness of the listing did not negate the fact that the compound claimed was specifically taught. The Board compared the facts to the situation in which the compound was found in the Merck Index, saying, "The tenth edition of the Merck Index lists ten thousand compounds. In our view, each and every one of those compounds is described' as that term is used in 35 U.S.C. § 102(a), in that publication."). Id. at 1718. See also In re Sivaramakrishnan, 673 F.2d 1383, 213 USPQ 441 (CCPA 1982) (The claims were directed to polycarbonate containing cadmium laurate as an additive. The court upheld the Board's finding that a reference specifically naming cadmium laurate as an additive amongst a list of many suitable salts in polycarbonate resin anticipated the claims. The Applicant had argued that cadmium laurate was only disclosed as representative of the salts and was expected to have the same properties as the other salts listed while, as shown in the application, cadmium laurate had unexpected properties. The court held that it did not matter that the salt was not disclosed as being preferred, the reference still anticipated the claims and because the claim was anticipated, the unexpected properties were immaterial.)."
Furthermore, a particularly preferred amount of Nrg-1β1 to be administered in Schrattenholz is 600 ng per kg body weight. See [0026], wherein the dosage is taught as one endpoint of a preferred range. This specific dosage is taught as therapeutically effective by this application’s specification. Thus, Schrattenholz’s administration of Nrg-1β1 for treatment of MS would result in the specific immunomodulatory mechanism of action discovered and recited in the amended claims. The claims require one active method step, i.e., administering Nrg-1β1 to multiple sclerosis subjects, which is explicitly taught by Schrattenholz. The remaining limitations set forth in the wherein clauses of claims 1 and 3 are not active method steps. Rather, they are statements regarding phenomena that naturally flow from practicing the active method steps of the claims. Since the combination of the prior art references set forth above teaches and suggests the active method steps of the claims, the remaining limitations referred to by applicant would necessarily occur upon administration.
Applicant asserts that the claimed method is not merely "administering Nrg-1β1" but is, more specifically, a method of treating a newly-identified deficiency state. Applicant asserts that Schrattenholz does not recognize the existence of the deficiency. Applicant asserts that the reason for administering the drug and its mechanism of action are fundamentally different between this application disclosure and Schrattenholz.
It is irrelevant that Schrattenholz whether Schrattenholz recognized “the newly identified deficiency state” disclosed by the specification of this application. Schrattenholz teaches and claims treating the same patient population with the same treatment agent at the same or overlapping therapeutically effective amounts, regardless of whether Schrattenholz considered this treatment agent to be neuroprotective, while applicant considers the agent to be immunomodulatory. In response to applicant's argument that Schrattenholz does not teach that Nrg-1β1 fosters a specific immunomodulatory effect by phenotype shift in microglia, macrophage and T lymphocytes from pro-inflammatory pathogenic to anti-inflammatory disease modifying state, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Therefore, the claims are anticipated and rendered obvious by Schrattenholz (and Johnson and Masuoka).
Conclusion
No claim is allowed.
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 GREGORY S EMCH whose telephone number is 571-272-8149. The examiner can normally be reached Monday - Friday, 7:30 am - 3:30 pm PT.
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/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
