DETAILED ACTION
Applicant’s amendment to the claims, in the Response filed on 10/27/2025, adding newly presented limitations and materially changing the scope of the claims, is acknowledged.
The rejections of record under 35 U.S.C. §§ 101, 102, and 112(d) and double-patenting rejections are withdrawn in view of Applicant’s amendment to the claims in the Response filed on 10/27/2025.
The rejections of record under 35 U.S.C. §§ 112(a) and 103 are maintained and modified in view of Applicant’s amendment to the claims in the Response filed on 10/27/2025 as set forth below.
Claim Rejections - 35 USC § 112-Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—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 or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 1-9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating amyotrophic lateral sclerosis (ALS) in mice, does not reasonably provide enablement for treating, preventing, alleviating and/or delaying the onset of motor neuron diseases (MNDs) in any subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The instant claims, as amended, are broadly drawn to a method of treating, preventing, alleviating and/or delaying the onset of motor neuron diseases (MNDs) in a subject, the method comprising intravenously administering to the subject, a cell preparation comprising, as an active ingredient, an effective amount of pluripotent stem cells positive for SSEA-3 isolated from mesenchymal tissue of a body or cultured mesenchymal cells. Instant claim 8 recites specific MNDs, i.e., amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), spinal muscular atrophy (SMA), progressive muscular atrophy (PMA), or spinal and bulbar muscular atrophy (SBMA). It is noted that the term “preventing” was interpreted in an absolute sense to mean to always keep something from happening or arising.
The level of skill in the art is high and would include, e.g., Ph.D. level scientists.
The exemplary embodiments in the Specification are limited to two amyotrophic lateral sclerosis (ALS) animal models, i.e., a mutant SOD1 (G93A) transgenic mouse model (Example 1) and a human transactive response (TAR) DNA binding protein 43 kDa (TDP-43) transgenic mouse model (Example 2), which demonstrate limited therapeutic efficacy for ALS in the mice. The Specification offers no working examples or reasonable direction to use SSEA-3-postive pluripotent stem cells for treating, preventing, alleviating and/or delaying the onset of any MND, including amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), spinal muscular atrophy (SMA), progressive muscular atrophy (PMA), or spinal and bulbar muscular atrophy (SBMA), in virtually any subject, including rodents, canines, felines, primates, humans, etc.
With respect to ALS, Vinsant et al. (Brain and Behavior, 3(4):335-350 (2013), prior art of record) evidences that “numerous preclinical trials have been conducted in the mutant SOD1 mouse models, the results have been disappointing because they did not positively translate to clinical trials” (Abstract). More generally, Hobson et al. (Medic. 44(9):552-556 (2016), prior art of record) evidences that MND is a disabling and ultimately fatal disease of the motor system, having a variable, unpredictable prognosis, with few effective treatments in virtually any subject (Abstract; page 554, Giving the diagnosis). Hobson further evidences that riluzole is the only drug licensed for treatment of ALS and only prolongs median survival by approximately 3 months (page 555, Pharmacological treatments). As such, there is little predictability in the art for treating, alleviating, or delaying the onset of MNDs—let alone the absolute prevention of MNDs in virtually any subject.
In view of the foregoing, a vast quantity of experimentation, including extensive clinical trials spanning various disease states, ALS, PLS, SMA, etc., would be needed to make the invention based on the content of the disclosure.
Accordingly, the Specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
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.
Claims 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Uccelli et al. (Mol. Med. 18:794-804 (2012), hereinafter “Uccelli”) in view of Dezawa (Cell Transplant., 25:849-861 (2016), hereinafter “Dezawa2”) as evidenced by Dezawa et al (WO 2011007900, prior art of record, hereinafter “Dezawa”).
Regarding claim 1, Uccelli teaches intravenous (IV) administration of mesenchymal stem cells (MSCs) improves survival and motor function in experimental Amyotrophic Lateral Sclerosis (ALS) mouse models (Abstract). The reference does not explicitly teach that the MSCs are pluripotent stem cells positive for SSEA-3 isolated from mesenchymal tissue of a body or cultured mesenchymal cells, as claimed. It is noted that the claimed stem cells are Muse cells (see Abstract; Specification, as published, ¶¶ 0103-0111).
Dezawa2 teaches Muse cells, a subset of MSCs, are able to generate cells representative of all three germ layers from a single cell, and are nontumorigenic and self-renewable (Abstract). Dezawa2 further teaches that “Muse cells are particularly unique compared with other stem cells in that they efficiently migrate and integrate into damaged tissue when supplied into the bloodstream, and spontaneously differentiate into cells compatible with the homing tissue. Such a repairing action of Muse cells via intravenous injection is recognized in various tissues including the brain, liver, and skin” (Abstract). Dezawa2 teaches “Muse cells render induction into the target cell type prior to transplantation unnecessary. They can repair tissues in two simple steps: collection from mesenchymal tissues, such as the bone marrow, and intravenous injection. The impressive regenerative performance of these cells provides a simple, feasible strategy for treating a variety of diseases” (Abstract).
One of ordinary skill in the art would have been motivated to use the Muse cells taught by Dezawa2 in the method taught by Uccelli due to the specific and advantageous properties of Muse cells compared to other MSCs with a reasonable expectation of success.
Regarding claim 2, Dezawa2 teaches concentrating the pluripotent stem cells positive for SSEA-3 by external stress treatment, thereby obtaining a cell fraction for IV administration (FIG. 7).
Regarding claim 3, Dezawa2 teaches that the stem cells are CD105-positive (FIG. 2).
Regarding claim 4, as evidenced by Dezawa, Muse cells are CD117-negative and CD146-negative (page 4, [4]).
Regarding claim 5, as evidenced by Dezawa, Muse cells are CD117-negative, CD146-negative, NG2-negative, CD34-negative, vWF-negative, and CD271-negative (page 4, [4]).
Regarding claim 6, as evidenced by Dezawa, Muse cells are CD34-negative, CD117-negative, CD146-negative, CD271-negative, NG2-negative, vWF-negative, Sox10-negative, Snai1-negative, Slug-negative, Tyrp1-negative, and Dct-negative (page 4, [4]-[5]).
Regarding claim 7, as evidenced by Dezawa, Muse cells: i) have low or no telomerase activity (page 4, [6]; ii) have the ability to differentiate into any of three germ layers (page 5, [7]); iii) exhibit non-tumorigenic proliferation (page 5, [8]); and iv) have self-renewal ability (page 5, [9]; see also Dezawa2, Abstract).
Regarding claim 8, Uccelli teaches an ALS mouse model (Abstract).
Regarding claim 9, given that Dezawa2 teaches Muse cells and the instant claims are drawn to Muse cells, absent evidence to the contrary, the Muse cell taught by Dezawa2 have the ability to engraft into the spinal cord. “Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments filed 10/27/2025 have been fully considered but they are not persuasive. Applicant’s arguments are discussed to the extent they apply to the current grounds of rejection set forth above.
On pages 4-5 of the Response, Applicant urges “that the present specification provides a disclosure sufficient for a person skilled in the art to understand methods for treating, preventing, alleviating, and/or delaying the onset of motor neuron disorders using Muse cells.”
Applicant’s data is limited to only ALS mouse models. As discussed above, Vinsant evidences that “numerous preclinical trials have been conducted in the mutant SOD1 mouse models, the results have been disappointing because they did not positively translate to clinical trials” (Abstract). As such, given, inter alia, the unpredictability between ALS mouse models and clinical outcomes, the limited data in the Specification does not reasonably demonstrate that Muse cells can be IV administered for treating, preventing, alleviating, and/or delaying the onset of ALS, let alone all motor neuron disorders (SMDs), as claimed. Nothing in the Specification remotes demonstrates that Muse cells facilitate the absolute prevention of all SMDs, including amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), spinal muscular atrophy (SMA), progressive muscular atrophy (PMA), or spinal and bulbar muscular atrophy (SBMA), in any subject, including humans. Indeed, the Specification is limited to only the ALS mouse model and provides no data concerning other SMDs such as PLS, SMA, PMA, SBMA, progressive bulbar palsy (PBP), Kennedy’s disease, post-polio syndrome (PPS), etc.
In view of the foregoing, the rejections of record are maintained.
Conclusion
NO CLAIMS ARE 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 THOMAS J VISONE whose telephone number is (571)270-0684. The examiner can normally be reached Monday-Thursday, 8:30 AM to 6:30 PM.
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/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672