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 .
Election/Restrictions
Claims 1-6, 10 are pending.
Cl. 1-6 and elected Group I are examined here and claim 10 stands withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
A certified English translation was made of record, see 06/02/2026.
Priority to the Foreign Priority Application, KR10-2020-01400438, filed 10/27/2020, and the PCT application (PCT/KR2021/013970), filed on 10/12/2021, is recognized.
All examined claims enjoy priority to the date of foreign application ‘438’s filing, 10/27/2020.
Drawings
The objection will be maintained until the petition is granted. The petition has not been granted as of filing of this action.
Color photographs and color drawings (Fig. 1A, 4, 5, 6, 9, 10, 11, 13) are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Response to Arguments
Applicant's arguments filed 06/02/2026 (“the Remarks”) have been fully considered but they are not persuasive.
The Remarks suggest that “in view of the accompanying petition. . . the color drawings are acceptable” (pg. 6). This is argument is not persuasive. Submission is one step of the process and the petition needs to be reviewed if the conditions are met for accepting color drawings. Thus, the objection is maintained.
Specification
The objection regarding description of drawings lacking panel designation 1A and 1B is withdrawn, the specification amendment of 06/02/2026 notes both panels.
Claim Rejections - 35 USC § 112
35 U.S.C. 112(b)
Rejection of claims 1, 2, and 3 under 112(b) is withdrawn as claims 1 and 2 have been amended to delete the terms “protecting” and “protection”.
35 U.S.C. 112(a)
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 1-3 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
It should be made clear that, the enabling specification must teach those skilled in the art to make and use the full scope of the claimed invention without undue experimentation. “Although not explicitly stated in section 112, to be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without "undue experimentation." Vaeck, 947 F.2d at 495, 20 USPQ2d at 1444; Wands, 858 F.2d at 736-37, 8 USPQ2d at 1404; In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (the first paragraph of section 112 requires that the scope of protection sought in a claim bear a reasonable correlation to the scope of enablement provided by the specification).” In re Wright (CAFC) 27 USPQ2d 1510 at 1513. Although a working example is not required to enable an invention, the skilled artisan must be able to practice the claimed invention without undue experimentation. See also, MPEP §2164.02, which states in part: The specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970). Lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.
Claims 1 and 2 explicitly encompass preventing damage to motor neuron cells or prevents degenerative damage in a subject. Looking to the prior art for guidance, a search of the prior art did not identify any methods which effectively prevent damage or degenerative damage in a subject. The specification also does not provide any working example demonstrating prevention of damage to motor neuron cells or prevent degenerative damage to motor neurons in a subject. Therefore, given the lack of knowledge present in the prior art and the lack of guidance provided in the specification with respect to preventing damage or prevent degenerative damage in a subject, further experimentation would be required. Considering that the additional experimentation would require de novo experimentation without a guarantee of success, and further considering that any positive results (i.e., successful prevention of damage to motor neurons cells/prevent degenerative damage in a subject) would amount to a significant advancement in the state of the art, the additional experimentation required is considered undue.
Furthermore, in In re Vaeck, 947 F.2d 488,495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991), the Court ruled that a rejection under 35 U.S.C. 112, first paragraph for lack of enablement was appropriate given the relatively incomplete understanding in the biotechnological field involved, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims. Such is the case here, where there is a relatively incomplete understanding in the biotechnological field involved, as described above, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims.
Claim 3 depends on claim 1 and fails to overcome the enablement rejection.
Therefore, it is appropriate to reject the claims under 35 USC 112(a) for not being enabled to their full scope.
Claims 1-3 will not be examined under the art rejections.
Improper Markush Group
Rejection of claim 6 under improper Markush group is withdrawn, Huntington’s Disease is deleted from the claim.
Claim Rejections - 35 USC § 103
Rejection of cl. 4-6 is maintained.
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.
Claims 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Kang et al. (2013, Nature Neuroscience, 16, 571-581, “Kang”) and Wang et al. (2016, Glia, 64, 1021-1033, only the abstract is provided, “Wang”).
Kang discloses that amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease exhibiting death of motor neurons with progressive muscle weakness and is linked to glial cell dysfunction (pg. 571, relevant to instant cl. 4-6 (neuromuscular disease ALS)). Kang discloses that in ALS patients and in SOD1 (G93A) mouse model of ALS, glial cells called oligodendrocytes, and their progenitor cells, NG2+, appear dysfunctional and also affects motor neuron survival (pg. 571, relevant to instant cl. 4-6). Oligodendrocytes protect neurons by providing myelin sheathing and metabolic support (pg. 571). Kang demonstrates progressive degeneration of oligodendrocytes in the spinal cord of SOD1 (G93A) mouse model of ALS and human ALS patients by exhibiting abnormal morphologies and failing to fully differentiate, as demonstrated by increased demyelination (Pg. 571, 576-577). Kang discloses that the oligodendrocytes provide metabolic support to neurons (pg. 571). Kang also discloses that vulnerability to oligodendrocytes may be exacerbated by the presence of pro-inflammatory cytokines (pg. 571). Kang also discloses that oligodendrocyte loss is expected to have negative effect on the survival of motor neurons in ALS disease (pg. 571). Deletion of SOD1 gene in NG2+ cells, which differentiate into oligodendrocytes, delayed onset of the disease, thus confirming the role of oligodendrocytes in ALS (pg. 577).
Kang does not disclose administering gene encoding Cdo or Cdo protein to a subject in need.
Wang demonstrates a role of Cdon in oligodendrocyte differentiation and myelination by overexpressing full length Cdon to show increased oligodendrocyte branching and contact point numbers with axons when cocultured with dorsal root ganglion neurons (abstract, relevant to instant cl. 4-6). (Cdo is also known as Cdon).
One of the KSR rationale that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the filing date of the claimed invention to have modified the ALS mouse model of Kang by over-expressing the full-length Cdon of Wang and arrive at the claimed invention with a reasonable expectation of success. Based on the success of Wang demonstrating that overexpression of Cdon improved oligodendrocyte differentiation and myelination, along with increased contact point numbers with axons when co-cultured with dorsal root ganglion neurons, a skilled artisan would reasonably expect success by administering an expression vector encoding a full-length Cdon of Wang to the ALS mouse model of Kang to improve myelination of axons, thus protecting the damaged motor neuron axons by preventing damage due to inflammation and to increase reinnervation and to treat the neuromuscular disease ALS. Thus, cl. 4-6 are obvious.
Response to Arguments
Applicant's arguments filed 06/02/2026 have been fully considered but they are not persuasive.
The Remarks of 06/02/2026 argues the following:
1. The prior art do not teach/suggest all elements of instant claims: Kang relates to oligodendroglial dysfunction in ALS pathology rather than therapeutic prevention of motor neuron damage and that Kang does not disclose "abnormalities in oligodendrocytes and NG2+ progenitor cells in ALS affect motor neuron survival and that oligodendrocytes protect motor neurons through myelin sheathing and metabolic support” (pg. 10). The Remarks contend Kang is a discussion of "pathophysiological study reporting oligodendrocyte degeneration and demyelination in SOD1 (G93A) ALS mouse model and human ALS patients” and “demonstrates the relationship between oligodendroglial dysfunction and motor neuron vulnerability. Kang is directed to understanding how damage occurs through disease-related mechanisms, rather than how to prevent damage through therapeutic intervention" (pg. 10). Then to highlight this point, the Remarks note that "Figure 8 of Kang which shows genetic deletion of mutant SOD1 in oligodendroglial lineage cells, which is directed to understanding disease-related mechanisms rather than therapeutic administration of a protein or gene to prevent motor neuron damage. This genetic deletion approach operates in a different conceptual framework than the therapeutic approach of the present invention" (pg. 10).
2. Then the Remarks contends that Wang "relates to oligodendrocyte differentiation and myelination at the cellular level, rather than motor neuron preservation at the organismal level" and that "increased axon contact points described in Wang reflect cellular-level interaction in vitro and would not necessarily translate to prevention of motor neuron damage in living organisms" nor "suggest therapeutic approaches to neuromuscular diseases" (pg. 11).
3. Then the Remarks argue that combination of Kang and Wang is based on impermissible hindsight reconstruction (pg. 12).
4. The Remarks argue several gaps, a) divergent disease context, b) absence of therapeutic administration in the references and c) cellular-level improvement does not automatically translate to organismal-level functional recovery and d) absence of age-related neuroprotection. The divergent disease context is that Kang operates in an ALS pathological environment where oligodendrocytes are already degenerating, while Wang operates in a normal biological environment where the role of Cdon in promoting oligodendrocyte differentiation is observed, thus not obvious to combine the references. There is also a lack of therapeutic administration, since Wang only administers in cell culture and Kang discusses SOD1 gene deletion to elucidate the etiology of motor neuron damage "a reductionist approach aimed at identifying disease causation, not disease prevention" (pg. 13). Both teachings are "fundamentally different from the concept of administering a Cdo protein to a living organism to achieve therapeutic benefit". Third, cellular-level observation does not translate to prevention of loss of motor neuron survival in living animals, preservation of motor function (locomotor ability, muscle strength), stabilization of neuromuscular junction integrity, etc. . . (pg. 13-14).
The argument is not persuasive.
First, arguments will focus on arguments relevant to cl. 4-6, since the amended claims 1-3 are rejected under 35 USC 112(a) enablement and are not rejected under 103.
The Examiner has met the prima facie standard of obviousness under 103 for cl. 4-6 and a reasonable success does not require a certainty in the outcome. Since the Remarks lack any evidence why in vitro results would not translate to an in vivo mouse model, a skilled artisan would reasonably expect success in administration of gene encoding Cdo to aid in treating ALS mouse model, regardless of a) how the ALS model was generated, including using a mutant SOD1, nor b) what is the root cause of ALS, which is recited as a motor neuron disease.
Here, the rationale is provided for combination of Kang and Wang. Kang uses a mutant SOD1 ALS mouse model to demonstrate “extensive degeneration of gray matter oligodendrocytes in the spinal cord” and extensive demyelination of the ALS mouse model, which is similar to observation noted in human ALS (see action of 03/03/2026, pg. 7-8). Although Kang indicates one way to decrease ALS symptoms, it is not the only way, as Wang provides that administration of full-length rat Cdon increased myelin biomarkers, i.e. myelination, and increases the number of contact points with axons of dorsal root ganglion neurons. Thus, a skilled artisan would reasonably expect that administration of Cdon expression vector in an ALS mouse model would increase myelination based on increased myelination and axonal reinnervation. Just because Wang’s study is of early nervous system development, does not mean that Cdon’s administration would not result in similar observation in vivo without evidence indicating otherwise.
Here, cl. 4-6 does not specifically require administration to a subject, but rather a generic claim of administering a gene encoding Cdo protein. The claims lack any specificity of administration, i.e. who, where, how and how much, and when. Regardless, the action did note in the conclusion of “administering the full-length Cdon of Wang to the ALS mouse model of Kang,” thus the rejection fulfilled the minimum requirement of administering the expression vector to a subject in need, even though it is not claimed.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). First, the specification does not demonstrate administration of Cdo, neither in vitro nor in vivo; it is merely a suggestion and only demonstrates the expression of endogenous Cdo (i.e. the Fig. 9/10, pg. 21). Here, both the prior arts disclosure are prior to the effective filing date of instant application, and Wang specifically discloses the remyelination and improving reinnervation following administering a Cdo gene.
The Remarks details various factors and issues that are not claimed, i.e. the cause of ALS, cardiotoxin treatment effects on a Cdo-deficient mice, divergent disease context, the examples of the specification, reductionist approach, etc. . ., thus these factors/issues are not relevant.
Thus rejection to cl. 4-6 is maintained under 103.
Allowable Subject Matter
No claim allowed.
Conclusion
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 KEYUR A. VYAS whose telephone number is (571)272-0924. The examiner can normally be reached M-F 9am - 4 pm (EST).
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/KEYUR A VYAS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600
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