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 .
DETAILED ACTION
Status of Application/Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-3, 8, 11, 14-16 and 48) and a combination of N-acetyl cysteine (NAC) and an anti-IL-17A antibody for species of agent and IL-17A for species of pro-inflammatory cytokine in the reply filed on February 26, 2026 is acknowledged.
Claims 4-7, 9-10, 12-13, 17-31, 39-41, 44 and 46 are canceled. Claims 3, 8 and 42-43 are amended. Claims 1-3, 8, 11, 14-16, 32-38, 42-43, 45 and 47-48 are pending. Claims 32-38, 42-43, 45 and 47 are withdrawn without traverse (filed 02/26/2026) from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 26, 2026.
Claims 1-3, 8, 11, 14-16 and 48 are under examination with respect to a combination of N-acetyl cysteine (NAC) and an anti-IL-17A antibody for agent and IL-17A for pro-inflammatory cytokine in this office action.
Specification
The disclosure is objected to because of the following informalities: The use of the term “Matrigel” (p. 68), “MAGPIX” “xPONENT” (p. 69), or “FlowJo” (p. 70), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Appropriate correction is required.
Claim Objections
Claims 32-38, 42-43, 45 and 47 are objected to because of the following informalities: the status of the claims 32-38, 42-43, 45 and 47 is incorrect because these claims are withdrawn from consideration. Appropriate correction is required.
See MPEP 714 & 37 CFR 1.121.
“In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).”
Claims 3 and 8 are objected to because of the following informalities: the limitation “anti-IFN-g” recited in claim 3 should be “anti-IFN-g”. The limitations “IFNa2”, “IFN-g” and “IL-1Ra” should be “IFNa2”, “IFN-g” “IL-1Ra”. The recitations “FIT3L”, “MCP3”, “MDC”, “MCP1”, “IP-10”, “MIP-3a”, “MIP-1a” and “MIP-1b” are not unique or common abbreviations in the art. Applicants are required to spell out “FIT3L”, “MCP3”, “MDC”, “MCP1”, “IP-10”, “MIP-3a”, “MIP-1a” and “MIP-1b” at the first usage. Appropriate correction is required.
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 1-3, 8, 11, 14-16 and 48 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 pre-AIA the applicant regards as the invention.
Claims 1-3, 8, 11, 14-16 and 48 are indefinite because
i. Claim 1 recites the limitation "the level" in line 3 of the claim. There is insufficient antecedent basis for this limitation in the claim.
ii. The rest of claims are indefinite as depending from an indefinite claim.
Claim Rejections - 35 USC § 112
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, 8, 11, 14-16 and 48 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 neutralizing and reducing increased levels of IL-17A detected in serum or CSF of patients with Amyotrophic lateral sclerosis (ALS) by administering to the patients a structurally and functionally defined anti-IL-17A in combination with N-Acetyl-Cysteine when compared to ALS patients without treatment, does not reasonably provide enablement for methods of treating all forms of neurodegenerative diseases or inhibiting degeneration and/or death of a nerve cell in a subject using at least one structurally and functionally undefined agent that decreases levels of one or more pro-inflammatory cytokines, chemokines and/or growth factors as broadly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. In addition, the specification does not enable the invention of claims 1-3, 8, 11, 14-16 and 48 that is directed to a method of prevention of all forms of neurodegenerative diseases.
“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)”. See MPEP § 2164.01.
Claims 1-3, 8, 11, 14-16 and 48 as amended are drawn to a method of treating a neurodegenerative disease in a subject in need thereof, or a method of inhibiting degeneration and/or death of a nerve cell in a subject, the method comprising administering to the subject at least one agent that decreases the level of one or more pro-inflammatory cytokines, chemokines and/or growth factors.
The claims encompass treating and preventing all forms of neurodegenerative diseases or inhibiting degeneration and/or cell death of nerve cells in a subject caused by all possible conditions using a structurally and functionally undefined agent that decrease the level of one or more undefined pro-inflammatory cytokines, chemokines and/or growth factors in view of p. 18 of instant specification or paragraph [0220] of the published application.
The instant invention is based on characterizations and comparisons of immune response and immune cell profiles between ALS patients and healthy controls or a healthy twin control. Based on Applicant’s own admission, there is no difference or a slight change in most immune cell profiles between ALS patients and healthy controls or a healthy twin except IL-2+anti-CD3/CD28 treated PBMCs of ALS patients (see examples). The specification also disclosed that “variable results in IFN-g spots but higher secretion of IFN-g by the majority treatments in NK cells in ALS patient in comparison to twin control” (see p.133 of the specification).
Applicant extrapolates the above findings to the claimed method of treating including preventing a neurodegenerative disease or inhibiting degeneration and/or cell death of nerve cells in a subject caused by all possible conditions using an agent that decreases the level of one or more undefined pro-inflammatory cytokines, chemokines and/or growth factors.
First, Applicant is not enabled for a method of treating including preventing a neurodegenerative disease including all forms of CNS neurodegenerative diseases including ALS, Alzheimer’s disease (AD), Parkinson’s disease (PD), motor neuron disease (MND), Batten Disease (BD), Huntington’s disease (HD) or Muscle Atrophy (MA) caused by all possible mechanisms. Based on paragraph [0220] of the published specification, the definition of “treating/treatment” encompasses prevention of all forms of CNS neurodegenerative diseases including ALS, AD, PD, MND, BD, HD or MA caused by all possible mechanisms.
[0220] The term “treating” includes prophylactic and/or therapeutic treatments. The term “prophylactic or therapeutic” treatment is art-recognized and includes administration to the host of one or more of the subject compositions. If it is administered prior to clinical manifestation of the unwanted condition (e.g., disease or other unwanted state of the host animal), then the treatment is prophylactic (i.e., it protects the host against developing the unwanted condition)…..
However, neither the specification nor the prior art provides guidance as to how to prevent a person from having a neurodegenerative disease including ALS, AD, PD, MND, BD, HD or MA caused by all possible mechanisms. Any individual has a potential to develop any neurodegenerative disease including ALS, AD, PD, MND, BD, HD or MA caused by all possible mechanisms. The causes of different forms of neurodegenerative diseases including ALS, AD, PD, MND, BD, HD or MA caused by all possible mechanisms caused are different. There are many factors involved in molecular mechanisms contributing to pathogenesis of ALS, AD, PD, MND, BD, HD or MA. For example, several genes have been found to be associated with familial ALS, including SOD1, TARDBP, FUS, UBQLN2, PFN1, OPTN, VCP, MATR3, TUBA4A, C9ORF72, NEK1, KIF5A, VCP, ALS2, SETX, ANG, CHCH10, SQSTM1, TBK1 and CCNF in view of Williams et al. (Nat. Commun. 2016;7:11253. DOI:10.1038/ncomms11253), Ranganathan et al. (Front. in Neurosci. 2020; doi:10.3389/fnins.2020.00684), Bruijn et al. (Annu. Rev. Neurosci. 2004, 27: 723-49) and Limone et al. (Sci. Transl. Med., 2024; 16:eadg7895, p.1-16). The pathogenesis mechanisms for different forms of ALS are also independent and distinct from each other as evidenced by Ju et al. (PLoS Biology 2011; 9: 1-17; e1001052) and Lagier-Tourenne et al. (see table 1, Human Mol. Genet. 2010; 19: R46-R64 published online Apr 15, 2010; doi:10.1093/hmg/ddq137). The same issues applied to other neurodegenerative diseases; for example, Moore et al. teach that the pathogenesis of PD can be familial and associated with different gene deficits including a-synuclein, parkin, PINK1, LRRK, NR4A2 etc. (see p. 59-71, Moore et al., Annu. Rev. Neurosci. 2005; 28:57-87).
Applicant fails to teach how to identify or predict when and which person among us would be susceptible to such a disease or developing the disease, and predict when the person would need the treatment of the claimed agent that decreases the level of one or more pro-inflammatory cytokines, chemokines and/or growth factors to prevent the disease before the disease occurs. Neither the specification nor the prior art teaches that administration of the claimed agent can prevent a person from getting any neurodegenerative disease including ALS, AD, PD, MND, BD, HD or MA caused by all possible mechanisms. If the cause is due to genetic deficits or mutations, it is impossible to prevent a person from getting or developing any neurodegenerative disease including ALS, AD, PD, MND, BD, HD or MA caused by all possible mechanisms because the gene mutation or gene deficiency is a natural process result.
Further, the specification fails to provide sufficient guidance as to what specific amount of the claimed agent can be used, and thus would be effective to prevent all forms of neurodegenerative diseases including ALS, AD, PD, MND, BD, HD or MA caused by all possible mechanisms. Thus, a skilled artisan cannot contemplate a right amount to prevent the disease or to prevent a person from getting the disease, indicating undue experimentation is required by a skilled artisan to perform while practicing the claimed method to treat and prevent all forms of neurodegenerative diseases including ALS, AD, PD, MND, BD, HD or MA caused by all possible mechanisms using the claimed structurally and functionally undefined agent that decreases undefined pro-inflammatory cytokines, chemokines and/or growth factors.
Second, based on the specification and the prior art, Applicant is predictably enabled for neutralizing increased levels of IL-17A in serum and CSF in ALS patients by a structurally and functionally defined anti-IL-17 antibody alone or in combination with N-Acetyl-Cysteine (NAC) in view of Hsieh et al. (US9663587) and Sahasrabudhe et al. (p. 10, section 5.2.1, Sahasrabudhe et al., Antioxidants, 2023; 12:1316. Doi.org/10.3390/antiox12071316).
The claims are not limited to the agents and methods set forth above but also encompass treating all forms of neurodegenerative disease including ALS, AD, PD, MND, BD, HD or MA caused by all possible mechanisms using the claimed structurally and functionally undefined agent that decreases undefined pro-inflammatory cytokines, chemokines and/or growth factors. However, the specification fails to provide sufficient guidance to enable one of skill in the art to practice the full scope of the claimed invention without undue experimentation because of the complexity and unpredictability of the diseases and failure to provide support a correlation between the immune cell profiles of ALS patients and the pathogeneses or causes of all forms of neurodegenerative diseases including all forms of ALS, AD, PD, MND, BD, HD or MA caused by all possible mechanisms in vivo in view of Williams et al., Ranganathan et al., Bruijn et al., Ju et al. and Lagier-Tourenne et al..
Amyotrophic lateral sclerosis is characterized by the slow but inevitable degeneration of α motor neurons in the spinal cord ventral horns and brainstem and neurons in the motor cortex leading to eventual paralysis and death. It is also well known that the major pathological observations in ALS are muscle weakness, and selective degeneration of motoneurons in the patient’s cortex, brainstem and spinal cord. Mutations in genes SOD1, TARDBP, FUS, UBQLN2, PFN1, OPTN, VCP, MATR3, TUBA4A, C9ORF72, NEK1, KIF5A, VCP, ALS2, SETX, ANG, CHCH10, SQSTM1, TBK1 and CCNF as taught by Williams et al., Ranganathan et al. and Bruijn et al.
While mutations in SOD-1, TARDBP, FUS/TLS and CCNF have been identified and considered as causative for familial ALS, the pathogenesis of ALS is multifactorial. TDP-43 aggregates can only be found in sporadic ALS patients. The pathogenesis mechanisms for different forms of ALS are also independent and distinct from each other as evidenced by Ju et al. (PLoS Biology 2011; 9: 1-17; e1001052) and Lagier-Tourenne et al. (see table 1, Human Mol. Genet. 2010; 19: R46-R64 published online Apr 15, 2010; doi:10.1093/hmg/ddq137). The same issues applied to other neurodegenerative diseases, for example, Moore et al. teach that the pathogenesis of PD can be familial and associated with different gene deficits including a-synuclein, parkin, PINK1, LRRK, NR4A2 etc. (see p. 59-71, Moore et al., Annu. Rev. Neurosci. 2005; 28:57-87).
There is no established correlation among these different forms of neurodegeneration, it is unpredictable whether detecting an increased level of IL-17A or IFN-g in ALS patients can be identified in other forms of neurodegeneration caused by different mechanisms. Since the prior art has not deciphered the causes of ALS and other neurodegenerative diseases caused by all possible mechanisms, it is unpredictable what etiology and molecular mechanisms in all forms of neurodegenerative diseases including all forms of ALS, AD, PD, MND, BD, HD or MA caused by all possible mechanisms caused by all possible mechanisms are, and whether the claimed method can be used for treating all forms of neurodegenerative diseases including all forms of ALS, AD, PD, MND, BD, HD or MA caused by all possible mechanisms caused by all possible mechanisms in vivo, indicating that the undue experimentation is required by a skilled artisan to perform while practice the claimed invention.
In addition, the specification fails to provide sufficient guidance as to what structural and functional relationship between the claimed structurally and functionally undefined agents and the anti-IL-17A antibody known in the art such as the anti-IL-17A antibody disclosed in Hsieh et al. (US9663587 or US9481735) or Alberici (US9676847). Further, Sahasrabudhe et al. teach that a randomized, double-blind, controlled trial of NAC in ALS patients failed to provide benefits to ALS or change the disease progression parameters when compared to the placebo patient group and that “NAC has not been recommended as a potential treatment strategy to extend survival in ALS patients” (see p. 11; Sahasrabudhe et al., Antioxidants, 2023; 12:1316. Doi.org/10.3390/antiox12071316). It is not known what other agents are and thus can be used in the claimed method, indicating undue experimentation is required by a skilled artisan to perform while practicing the claimed invention. The skilled artisan cannot contemplate how to make and use the claimed method without undue experimentation.
Therefore, in view of the breadth of the claims, the lack of guidance in the specification, no working examples, the unpredictability of inventions, and the current status of the art, undue experimentation would be required by one of skill in the art to perform in order to practice the claimed invention as it pertains to methods of treating a neurodegenerative disease in a subject in need thereof, or inhibiting degeneration and/or death of a nerve cell in a subject by administering to the subject at least one agent that decreases the level of one or more pro-inflammatory cytokines, chemokines and/or growth factors.
Claim Rejections - 35 USC § 112
Claims 1-3, 8, 11, 14-16 and 48 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
Claims 1-3, 8, 11, 14-16 and 48 encompass using a genus of structurally and functionally undefined agent that decreases the level of one or more pro-inflammatory cytokines, chemokines and/or growth factors. Claim 3 encompasses using a genus of anti-IL-6 antibody, a genus of anti-TNF-a antibody, a genus of anti-IFN-g antibody and a genus of anti-IL-17A antibody for treating a genus of neurodegenerative disease.
Applicant has not disclosed sufficient species for using the broad genus of structurally and functionally undefined agents that decrease the broad genus of one or more undefined pro-inflammatory cytokines, chemokines and/or growth factors or the broad genus of anti-IL-6 antibody, the broad genus of anti-TNF-a antibody, the broad genus of anti-IFN-g antibody and the broad genus of anti-IL-17A antibody for treating the broad genus of neurodegenerative diseases.
The specification only describes characterization and comparison of immune cell profiles between ALS patients and healthy controls or a healthy twin control.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is in possession of and what Applicant is claiming.
M.P.E.P. § 2163 instructs:
An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. . . .
An applicant may show possession of an invention by disclosure of drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole. . . .
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.”
This standard has not been met in this case. From the specification and the prior art, Applicant is in possession of using a structurally and functionally defined anti-IL-17A antibody such as the anti-IL-17antibody disclosed in Hsieh et al. (US9663587) alone or in combination with NAC to neutralize the increased level of IL-17A in serum or CSF detected in ALS patients as compared to no treatment.
However, Applicant is not in possession of using other structurally and functionally undefined agents that decrease the level of structurally and functionally undefined pro-inflammatory cytokines, chemokines and/or growth factors or the broad genus of anti-IL-6 antibody, the broad genus of anti-TNF-a antibody, the broad genus of anti-IFN-g antibody and the broad genus of anti-IL-17A antibody for treating the broad genus of neurodegenerative diseases.
The specification provides no identification of any particular portion of the structure that must be conserved for the claimed genus of agents or the claimed genus of pro-inflammatory cytokines, chemokines and/or growth factors or the claimed genus of anti-IL-6 antibody, anti-TNF-a antibody, anti-IFN-g antibody and anti-IL-17A antibody for treating the broad genus of neurodegenerative diseases. The instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of agents or the claimed genus of pro-inflammatory cytokines, chemokines and/or growth factors or the claimed genus of anti-IL-6 antibody, anti-TNF-a antibody, anti-IFN-g antibody and anti-IL-17A antibody. There is no description of the conserved regions which are critical to the function of the claimed genera. There is no information regarding the relation of structure of other agents to the function of the anti-IL-17antibody disclosed in Hsieh et al. (US9663587). There is no information regarding the relation of structure of other IL-6 antibodies, anti-TNF-a antibodies, anti-IFN-g antibodies and anti-IL-17A antibodies to the function of the anti-IL-17antibody disclosed in Hsieh et al. (US9663587).
Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other agents, IL-6 antibodies, anti-TNF-a antibodies, anti-IFN-g antibodies and anti-IL-17A antibodies might be. Since the common characteristics/features of other agents, IL-6 antibodies, anti-TNF-a antibodies, anti-IFN-g antibodies and anti-IL-17A antibodies are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of using the claimed genera of agents, IL-6 antibodies, anti-TNF-a antibodies, anti-IFN-g antibodies and anti-IL-17A antibodies for treating the genus of neurodegenerative diseases.
Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of agents, anti-IL-6 antibodies, anti-TNF-a antibodies, anti-IFN-g antibodies and anti-IL-17A antibodies for treating the genus of neurodegenerative diseases, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483.
Therefore, the claimed methods have not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
Claim Rejections - 35 USC § 112
Claim 3 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claim 3 as amended is directed to a method of treating a neurodegenerative disease in a subject in need thereof, or a method of inhibiting degeneration and/or death of a nerve cell in a subject, the method comprising administering to the subject at least one agent that decreases the level of one or more pro-inflammatory cytokines, chemokines and/or growth factors, wherein the at least one agent comprises (a).. (f) NAC and an anti-IL-17A antibody.
The instant claim now recites a new limitation “(f) NAC and an anti-IL-17A antibody”, which was not clearly disclosed in the specification and claims as filed, and now changes the scope of the instant disclosure as filed. Such a limitation recited in the present claim, which did not appear in the specification or original claims, as filed, introduces new concepts and violate the description requirement of the first paragraph of 35 U.S.C. 112.
The specification fails to disclose the new limitation “wherein the at least one agent comprises (f) NAC and an anti-IL-17A antibody”. The specification only discloses “anti-IL-6 antibodies, anti-TNF-a antibodies, anti-IFN-g antibodies” (see paragraphs [0008]; [0022]; [0210];[0288]-[0290] of the published application and original claims 3, 37-38). The specification provides no guidance as to what the agent comprising (f) NAC and an anti-IL-17A antibody is and its use in the claimed method. Accordingly, in the absence of sufficient recitation for the limitation “wherein the at least one agent comprises (f) NAC and an anti-IL-17A antibody”, the specification does not provide adequate written description to support the new limitation recited in claim 3. Support is not found for the new limitation “wherein the at least one agent comprises (f) NAC and an anti-IL-17A antibody” as disclosed in the original specification and thus the recitation constitutes new matter absent evidence for their support. Applicant is required to cancel the new matter in the reply to this office action. Alternatively, Applicant is invited to clearly point out the written support for the instant limitation.
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 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.
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 1-2, 8, 11, 14-15 and 48 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dugan et al. (US10407374, issued Sep 10, 2019, priority Oct 19, 2007).
Dugan et al. (US10407374) teach a method of treating different neurodegenerative diseases including ALS recited in claims 1-2 (see col.78-81, claims 1-20) in a subject in need thereof including mammal or human recited in claim 48 (see col.), comprising administering to the subject an anti-IL-6 antibody or a C60 malonic acid derivative, which is an agent that decreases the level of IL-6 as recited in claims 1, 8, 11 (see col. 17, line 57-col. 22, line 31; col. 35, lines 13-40). Dugan also teaches further administering to the subject at least one additional therapy including anti-IL-6 before, after or concurrently with the C60 malonic acid derivative, which meets the limitations recited in claims 11 and 14-15 (see col. 32, lines 56-col. 35, lines 12; col. 35, lines 13-40). Thus, claims 1-2, 8, 11, 14-15 and 48 are anticipated by Dugan et al. (US10407374).
Claims 1-2, 8, 11, 14-15 and 48 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hsieh et al. (US9663587, issued May 30, 2017, priority Mar 5, 2009).
Hsieh et al. (US9663587) teach a method of treating different autoimmune diseases including ALS as recited in claims 1-2 (see col. 21, line 28) in a subject in need thereof including mammal or human recited in claim 48 (see col. 44, lines 7-18), comprising administering to the subject a multivalent and multispecific binding protein binding to IL-17 and TNF-a, which can decrease the level of IL-17 and TNF-a as recited in claims 1, 8, 11 (see col. 19, lines 61 to col. 21, line 28). Hsieh also teaches further administering to the subject at least one additional therapy including cytotoxic agents, anti-angiogenic agents or TNF antagonists before, after or concurrently with the multivalent and multispecific binding protein binding to IL-17 and TNF-a, which meets the limitations recited in claims 11, 14-15 (see col.19, lines 44-60). Thus, claims 1-2, 8, 11, 14-15 and 48 are anticipated by Hsieh et al. (US9663587).
Claims 1-3, 8, 11, 14-15 and 48 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Goldenberg et al. (US9416197, issued Aug 16, 2016, priority Nov 1, 2013).
Goldenberg et al. (US9416197) teach a method of treating different autoimmune diseases including ALS and multiple sclerosis, which are neurodegenerative diseases as recited in claims 1-2 (see col. 31, line 45) in a subject in need thereof including mammal or human recited in claim 48 (see col.31, lines 10-12), comprising administering to the subject a bispecific or multispecific antibody comprising at least one anti-TNF-a and at least one anti-IL-6 antibody, which can decrease the level of TNF-a and IL-6 recited in claims 1, 8 and 11 (see col. 1, line 22-col. 4, line 61; col. 30, line 59-col.34, line 3; col.34, line 33-col. 44, Examples 1-6, claims1-12). Goldenberg also teaches further administering to the subject at least one additional therapy including anti-angiogenic agents, pro-apoptotic agents, hormones, hormone antagonists, chemokines, enzymes, immunomodulators, cytokines or other known agents before, after or concurrently with the bispecific antibody, which meets the limitations recited in claims 11 and 14-15 (see col. 3, lines 20-col.4, line 61; col. 28-30). Thus, claims 1-3, 8, 11, 14-15 and 48 are anticipated by Hsieh et al. (US9663587).
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 3 is rejected under 35 U.S.C. 103 as being unpatentable over Hsieh et al. (US9663587) or Goldenberg et al. (US9416197) in view of Romero et al. (US1159715, issued Mar 7, 2023, priority Jan 11, 2018).
Hsieh or Goldenberg is set forth above but does not teach that the at least one additional therapy is edavarone and/or riluzole.
Romero et al. (US1159715) teaches a method of treating ALS using a Des1 inhibitor and coadministration with edavarone and/or riluzole as a second therapeutic agent to provide synergic effects for treatment of ALS (see col. 51, lines 36-41).
A person of ordinary skill in the art would have recognized that selecting and applying the known edavarone and/or riluzole as a second therapeutic agent and the known technique disclosed by Romero to the method of Hsieh or Goldenberg would have yielded the predictable result of better treatment of ALS and resulted in an improved method.
Using and including the known edavarone and/or riluzole as a second therapeutic agent in the method of Hsieh or Goldenberg would provide synergic effects for the treatment of ALS and expand application of the method of Hsieh or Goldenberg, and would increase patient’s satisfaction with treatment of ALS using a combination therapy because edavarone and/or riluzole has been used as a second therapeutic agent for synergic effects for treatment of ALS.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known the known edavarone and/or riluzole as a second therapeutic agent and the known technique disclosed by Romero to the method of Hsieh or Goldenberg, and yield the predictable result of treating ALS.
Conclusion
NO CLAIM IS ALLOWED.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Otsmane et al. (NeuroReport, 2013; 25:49-54) teach a method of transiently delivering an anti-IFNg neutralizing antibody to the CSF of an animal model of ALS SOD1G93A retards motor function decline in the SOD1G93A mutant mice (see abstract; p. 51-53, immunotherapy against IFNg retards motor function decline of SOD1 mutant mice).
Beretta et al. (Neurobiol. Dis. 2003; 13:213-221) teach exposure of N-Acetyl-Cysteine lowers SOD1-G93A-induced ROS production in human neuroblastoma SH-SY5Y cells expressing SOD1-G93A (see abstract).
Louwerse et al. (Arch Neurol.1995; 52:559-564) teach a randomized, double-blind,controlled trial of N-Acetylcysteine in ALS at a dose of 50mg/kg per day for 12 months did not result in increasing in 12-month survival or reduction in disease progression (see abstract).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
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Chang-Yu Wang
March 20, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675