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.
Status of Claims
Claims 1-11 and 18-24 are pending. Claims 23-24 are withdrawn. Claims 1-11 and 18-22 are under examination.
Election/Restrictions
Applicant’s election without traverse of Species (a) glial cell, (b) TDP43, and (c) amyotrophic lateral sclerosis (claims 1-11 and 18-24) in the reply filed on 06/22/2026 is acknowledged.
Claims 23-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to the nonelected species, there being no allowable generic or linking claim. Election was made without traverse.
Claim Objections
Claims 9 and 21 are objected to because of the following informalities: The claims recite “Batten Disease ,” should be –Batten Disease, – because there is a gap in the recited comma punctuation.
Additionally, claim 9 currently has a comma at the end of the sentence but it needs a period punctuation. Claim 9 also recites “or other” should be – other – only because too many “or” phrases in a list of items. 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.
Claim 21 is 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 21, the phrase “such as Batten Disease…” renders the claim indefinite because it is unclear whether the limitations following the phrase “such as” are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-11 and 18-22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas and nature/natural phenomena without significantly more.
Step 1: The instantly claimed inventions are directed (1) a method of predicting progression of a neurological or neurodegenerative disease in a subject in need comprising detecting a modification of one or more disease markers in a glial cell or neuronal cell generated from a skin cell of the subject, compared to a glial cell or neuronal generated from a control cell; (2) a method of identifying a subject who is responsive to a therapeutic agent, comprising detecting a modification of one or more disease markers in a glial cell or neuronal cell generated from a skin cell of the subject, compared to a glial cell or neuronal cell generated from a control cell and wherein the modification is indicative of cells that are responsive to the therapeutic agent.; and (3) a method of determining effectiveness of a therapeutic agent in a subject, comprising detecting a modification of one or more disease markers in a glial cell or neuronal cell generated from a skin cell of the subject obtained from the subject after administration of the therapeutic agent, compared to a modification of one or more disease markers in a glial cell or neuronal cell generated from a skin cell of the subject obtained from the subject before administration of the therapeutic agent. Therefore, the instantly claimed inventions fall into one of the four statutory categories. (Step 1: YES)
ELIGIBILITY STEP 2A; WHETHER A CALIM IS DIRECTED TO A JUDICIAL EXCEPTION. First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in in Prong Two if the recited judicial exception is integrated into a practical application of that exception.
Step 2A Prong 1
Claim 1 recites the following steps which fall under the mental processes of abstract ideas and nature/natural phenomena:
In particular, claims 1-3 are drawn to predicting, identifying and determining a disease such as neurological or neurodegenerative disease with one or more disease markers in a glial cell or neuronal cell generated from a skin cell. Such limitations are directed to a judicial exception because the claim language clearly conveys the naturally occurring relationship between neurological or neurodegenerative diseases of a subject and the one or more disease markers in a glial cell. This constitutes law of nature/natural phenomena, as a natural correlation between the markers and diseases.
Additionally, predicting, identifying and determining a disease such as neurological or neurodegenerative disease by detecting a modification of one or more disease markers in a glial or neuronal cell generated from a skin cell (looking or observing) and comparing data are categorized as abstract ideas, namely mental processes/ concepts performed in the human mind (such as a person simply thinking and observing the data). Such step would read on purely mental activity such as a practitioner looking at a subject’s chart and thinking about the levels of markers and a control.
Claims 4-6 recite limitations related to the naturally produced process for the natural correlation between the markers and disease from glial cell.
Claims 7-8 recite the abstract ideas of observing the comparison between before and after administration of a therapeutic agent. Thus, this is a mental process performed in the human mind. Claims 9-11 recite limitations related to the naturally produced process for the natural correlation between the markers and disease from glial cell. Claims 18-19 recite limitations related to the naturally produced steps for the natural correlation between the markers and disease from glial cell. Claim 20 recites the limitation of abstract ideas of comparing and identifying naturally produced cells. Claims 21-22 recite the limitations related to the naturally produced process for the natural correlation between the markers and disease from glial cell. (Step 2A, Prong 1: YES).
Step 2A: Prong 2:
The Step 2A, Prong 2 analysis requires identifying whether there are any additional elements recited in the claim beyond the judicial exception(s) and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception. Besides the abstract ideas and natural correlations, the claims detecting the markers and therapeutic agent. When so evaluated, these additional elements represent mere data gathering that is necessary for use of the recited judicial exception and is recited at a high level of generality. In particular, these limitations are insignificant extra-solution activity to obtain data information from a treatment or data gathering of a disease. The additional element of administration of the therapeutic agent (claim 3) does not integrate the recited judicial exception into a practical application for the following reasons. Although this limitation indicates an administration of a therapeutic agent, it does not provide any information as to how the subject/patient is to be treated or what the treatment is but instead covers generic possibilities that may not be relevant to the disease. In fact, this limitation is recited at such a high level of generality. The administration of a therapeutic agent does not apply or use the judicial exception in a meaningful way. These limitations are directed at the limitations necessary to perform the recited judicial exceptions. When so evaluated, these additional elements represent mere data gathering that is necessary for use of the recited judicial exception and is recited at a high level of generality. These judicial exceptions are not integrated into a practical application for the following reasons. (Step 2A, Prong 2: NO).
Step 2B: In step 2B, it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP 2106.05. The claims do not include any additional steps appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception. The additional limitations in claims 1-11 and 18-22 are well-understood, routine, and conventional.
Meyer et al. (“Direct conversion of patient fibroblasts demonstrates non-cell autonomous toxicity of astrocytes to motor neurons in familial and sporadic ALS”, PNAS, January 14, 2014, vol. 111, no. 2, pgs. 829-832, IDS submitted 02/08/2024 (8 pages), cite no. 34) teach ALS and methods to convert adult human fibroblasts from living ALS patients to induced neuronal progenitor cells and subsequent differentiation into astrocytes (i-astrocytes) and non-cell autonomous toxicity to motor neurons is found following co-culture of i-astrocytes from familial ALS patients with mutations in superoxide dismutase or hexanucleotide expansion C9ORF72 the two most frequent causes of ALS (see abstract). Meyer teaches developed a coculture assay enabling the screening for therapeutics on astrocytes, differentiated from spinal cord autopsy-derived neuronal progenitor cells (see pg. 829, left col., para. 2). Meyer teaches fibroblast samples from one fALS patient carrying a SOD1 mutation, three ALS patients carrying the C9ORF72 expansion repeat as well as three sporadic ALS patients ranging in age from 51 to 81 were either collected by skin biopsy or purchased from established tissue banks (see pg. 830, left col., para. 1 of Results).
Foust et al. (“Therapeutic AAV9-mediated Suppression of Mutant SOD1 Slows Disease Progression and Extends Survival in Models of Inherited ALS”, Molecular Therapy, vol. 21 no. 12, pgs. 2148-2159, Dec. 2013) teach astrocytes derived from sporadic ALS patients and progression in two mouse models following therapeutic delivery using a single peripheral injection of an AAV0 encoding an shRNA to reduce the synthesis of ALS-causing human SOD1 mutants (see abstract and Figs. 1-3).
Haidet-Phillips et al. (“Astrocytes from familial and sporadic ALS patients are toxic to motor neurons”, Nature Biotechnology, vol. 29, no. 9, pgs. 824-828, published September 2011, IDS submitted 02/08/2024 (8 pages), cite no. 18) teach ALS is a fatal motor neuron disease (see abstract). Haidet-Phillips teaches cocultured motor neurons with ALS patient-derived fibroblasts (see pg. 826, left col., middle of para. 2).
Liu et al. (“Direct Lineage Reprogramming Reveals Disease-Specific Phenotypes of Motor Neurons from Human ALS Patients”, Cell Reports, vol. 14, pgs. 115-128, published January 5, 2016) teach hiMNs (human induced motor neurons) converted from ALS patient fibroblasts show disease-specific degeneration manifested through poor survival, some shrinkage, hypoactivity, and an inability to form NMJs (see abstract). Liu teaches efficient conversion of ALS patient fibroblasts to hiMNs by applying the same reprogramming process to skin fibroblasts derived from three ALS patients aged between 37 and 50 years and these patients were identified to harbor genetic mutations in the FUS gene, including a synonymous mutations and ALS-patient-derived fibroblasts could be efficiently reprogrammed into neurons with 80%-93% of surviving NSIL-transduced cells expressing TUBB3 by 14 dpi and the converted cells also expressed the pan-neuronal markers MAP2 and NF200 (see pgs. 118-119, under Efficient Conversion of ALS Patient Fibroblasts to hiMNs).
Therefore, these additional elements when viewed alone and in combination are not sufficient to amount to significantly more than the recited judicial exception. When taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself. (Step 2B: NO).
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.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Meyer et al. (“Direct conversion of patient fibroblasts demonstrates non-cell autonomous toxicity of astrocytes to motor neurons in familial and sporadic ALS”, PNAS, January 14, 2014, vol. 111, no. 2, pgs. 829-832, IDS submitted 02/08/2024 (8 pages), cite no. 34).
Meyer teaches a rapid, highly reproducible method to convert adult human fibroblasts (i.e., skin cell) from living ALS patients to induced neuronal progenitor cells and subsequent differentiation into astrocytes (i-astrocytes) (i.e., glial cell) and non-cell autonomous toxicity to motor neurons is found following coculture of i-astrocytes from familial ALS patients with mutation in superoxide dismutase or hexanucleotide expansion C9ORF72 the two most frequent causes of ALS (abstract). Meyer teaches fibroblast samples from one fALS patient carrying a SOD1 mutation, three ALS patients carrying the C9ORF72 expansion repeat as well as three sporadic ALS patients ranging in age from 51 to 81 were either collected by skin biopsy or purchased from established tissue banks (see pg. 830, left col., para. 1 of Results; and Fig. 1). Fig. 1 shows direct conversion of human skin fibroblasts to tripotent iNPCs (also see caption). Fig. 3 shows skin derived astrocytes and SC derived astrocytes, which shows a control cell (SC derived astrocytes). Meyer teaches a method to model neurodegenerative diseases such as ALS and this tool now allows studying ALS while the patient is still alive and can help in testing potential therapeutics for individual patients (pg. 829, right col., under Significance), which would read on predicting progression of a neurological or neurodegenerative disease in a subject in need comprising detecting a modification of one or more disease markers in a glial cell or neuronal cell generated from a skin cell of the subject. Meyer teaches compared with the initial fibroblast lines, the differentiated i-astrocytes expressed higher levels of several astrocytic markers, including vimentin, CD44 antigen, as well as markers for mature astrocytes including s100 calcium binding protein B and glial fibrillar acidic protein (see pg. 830, last para.), which would read on compared to a glial cell or neuronal generated from a control cell.
With respect to claim 2, Meyer teaches fibroblast samples from one fALS patient carrying a SOD1 mutation, three ALS patients carrying the C9ORF72 expansion repeat as well as three sporadic ALS patients ranging in age from 51 to 81 were either collected by skin biopsy or purchased from established tissue banks (see pg. 830, left col., para. 1 of Results; and Fig. 1). These subjects are responsive to a therapeutic agent as the samples are ALS patients with SOD1 and the modification of SOD1 is indicative of cells that are responsive to the therapeutic agent. The recitation in the preamble of a subject who is responsive to a therapeutic agent is the intended purpose of the body of claims (i.e., steps) to find modifications. However, the steps have not included an active step of administering the therapeutic agent but rather finding modifications such as SOD1.
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.
Claims 1-11 and 18-22 are rejected under 35 U.S.C. 103 as being unpatentable over Meyer et al. (“Direct conversion of patient fibroblasts demonstrates non-cell autonomous toxicity of astrocytes to motor neurons in familial and sporadic ALS”, PNAS, January 14, 2014, vol. 111, no. 2, pgs. 829-832, IDS submitted 02/08/2024 (8 pages), cite no. 34) in view of Foust et al. (“Therapeutic AAV9-mediated Suppression of Mutant SOD1 Slows Disease Progression and Extends Survival in Models of Inherited ALS”, Molecular Therapy, vol. 21 no. 12, pgs. 2148-2159, Dec. 2013).
With respect to claims 1-3, Meyer teaches a rapid, highly reproducible method to convert adult human fibroblasts from living ALS patients to induced neuronal progenitor cells and subsequent differentiation into astrocytes (i-astrocytes) (i.e., glial cell) and non-cell autonomous toxicity to motor neurons is found following coculture of i-astrocytes from familial ALS patients with mutation in superoxide dismutase or hexanucleotide expansion C9ORF72 the two most frequent causes of ALS (abstract). Meyer teaches fibroblast samples from one fALS patient carrying a SOD1 mutation, three ALS patients carrying the C9ORF72 expansion repeat as well as three sporadic ALS patients ranging in age from 51 to 81 were either collected by skin biopsy or purchased from established tissue banks (see pg. 830, left col., para. 1 of Results; and Fig. 1). Fig. 1 shows direct conversion of human skin fibroblasts to tripotent iNPCs (also see caption). Fig. 3 shows skin derived astrocytes and SC derived astrocytes, which shows a control cell (SC derived astrocytes). Meyer teaches a method to model neurodegenerative diseases such as ALS and this tool now allows studying ALS while the patient is still alive and can help in testing potential therapeutics for individual patients (pg. 829, right col., under Significance). Meyer teaches easy production and expansion of i-astrocytes now enables rapid disease modeling and high-throughput drug screening to alleviate astrocyte-derived toxicity (see abstract). Meyer teaches compared with the initial fibroblast lines, the differentiated i-astrocytes expressed higher levels of several astrocytic markers, including vimentin, CD44 antigen, as well as markers for mature astrocytes including s100 calcium binding protein B and glial fibrillar acidic protein (see pg. 830, last para.). Meyer teaches generating induced NPCs (iNPCs) from adult human fibroblasts from patients who had been diagnosed with ALS and from age-matched healthy controls (see pg. 830, left col. para. 2).
Meyer teaches that these cultures of i-astrocytes and MNs (motor neurons) can be set up as high-throughput model systems and that potential therapeutics can now easily be tested on a variety of ALS backgrounds, including sporadic conditions in which the cause of disease is completely unknown. This approach could also help to improve the classification of patient subpopulations in sporadic cases based on their responsiveness to different drugs. Thus, direct conversion may be sufficiently fast to determine potential therapies that would be most promising for an individual patient with ALS, thereby opening the door to personalized modeling of toxicity in ALS (see pg. 831, right col., para. 2).
Although Meyer teaches potential therapeutics can be tested, the reference does not teach determining effectiveness of a therapeutic agent in a subject and detecting a modification of one or more disease markers in a glial cell or neuronal cell generated from a skin cell of the subject obtained from the subject after administration of the therapeutic agent.
Foust teaches mutations in SOD1 are linked to familial ALS resulting in progressive motor neuron death through one or more acquired toxicities and involvement of wt SOD1 has been linked to sporadic ALS, as misfolded SOD1 has been reported in affected tissue of sporadic patients and toxicity of astrocytes derived from sporadic ALS patients to motor neurons (see abstract). Foust further teaches injection of an adeno-associated virus serotype 9 (AAV9) encoding an shRNA to reduce the synthesis of ALS-causing human SOD1 mutants and AAV9 demonstrates to yield robust SOD1 suppression in motor neurons and glia throughout the spinal cord and therefore, setting the stage for AAV9-mediated therapy in human clinical trials (see abstract). Foust teaches mutant SOD protein expression in microglia and astrocytes significantly derives rapid disease progression, findings which have led to the conclusion that ALS pathophysiology is noncell autonomous (see pg. 2148, left col., para. 2). Foust teaches in Fig. 2(d-e) a P1 and P21 controls vs injected SOD1 mice with AAV9 (see caption and Fig. 3).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have used the method of Meyer with a potential therapeutic agent as taught by Foust because Meyer teaches that (1) these cultures of i-astrocytes and MNs (motor neurons) can be set up as high-throughput model systems and that potential therapeutics can now easily be tested on a variety of ALS backgrounds, including sporadic conditions and (2) this direct conversion may be sufficiently fast to determine potential therapies that would be most promising for an individual patient with ALS, thereby opening the door to personalized modeling of toxicity in ALS and Foust teaches AAV9 demonstrates a robust SOD1 suppression in motor neurons and glia throughout the spinal cord and therefore, setting the stage for AAV9-mediated therapy in human clinical.
Additionally, it would have been obvious to have compared the effectiveness of the therapeutic agent in the method of Meyer because Foust teaches comparing and monitoring the un-injected control with the injected AAV9 to determine the effectiveness of the therapeutic agent with respect to SOD1 levels and days.
The person would have a reasonable expectation of success in using the method of Meyer with a therapeutic agent because Meyer has recognized that its method is to determine potential therapeutics on a variety of ALS backgrounds and both Meyer and Foust understood the use of control and tested samples.
With respect to 4, Meyer teaches adult human fibroblasts from living ALS patients to induced neuronal progenitor cells and subsequent differentiation into astrocytes (i-astrocytes) (see abstract and Fig. 1).
With respect to claim 5, Meyer teaches adult human fibroblasts from living ALS patients to induced neuronal progenitor cells and subsequent differentiation into astrocytes (i-astrocytes) (see abstract and Fig. 1).
With respect to claim 6, Meyer teaches direct conversion of human skin fibroblasts to tripotent iNPCs (see Fig. 1 and caption).
With respect to claim 7, Meyer teaches that astrocytes carrying C9ORF72 expansion mutation also display toxicity toward MNs and mounting evidence for that involvement of misfolded SOD1 in sporadic ALS (see pg. 832, para. 1 of Discussion).
With respect to claim 8, Meyer teaches that astrocytes carrying C9ORF72 expansion mutation also display toxicity toward MNs and mounting evidence for that involvement of misfolded SOD1 in sporadic ALS (see pg. 832, para. 1 of Discussion and abstract). Thus, the wild-types C9ORF72 and SOD1 would decrease.
With respect to claim 9, Meyer teaches ALS (see abstract).
With respect to claim 10, Meyer teaches SOD1 and C9ORF72 would read on in vitro motor neuron toxicity (abstract).
With respect to claim 11, Meyer teaches ALS, SOD1 and C9ORF72 (abstract).
With respect to claim 18, Meyer teaches direct conversion of human skin fibroblasts to tripotent iNPCs (see Fig. 1 and caption).
With respect to claims 19-20, Meyer teaches adult human fibroblasts from living ALS patients to induced neuronal progenitor cells and subsequent differentiation into astrocytes (i-astrocytes) (see abstract and Fig. 1). Meyer teaches direct conversion of human skin fibroblasts to tripotent iNPCs (see Fig. 1 and caption).
With respect to claim 21, Meyer teaches ALS (see abstract).
With respect to claim 22, Meyer teaches mutations in SOD1 and C9ORF72 (abstract).
Claims 1-11 and 18-22 are rejected under 35 U.S.C. 103 as being unpatentable over Meyer et al. (“Direct conversion of patient fibroblasts demonstrates non-cell autonomous toxicity of astrocytes to motor neurons in familial and sporadic ALS”, PNAS, January 14, 2014, vol. 111, no. 2, pgs. 829-832, IDS submitted 02/08/2024 (8 pages), cite no. 34) in view of Foust et al. (“Therapeutic AAV9-mediated Suppression of Mutant SOD1 Slows Disease Progression and Extends Survival in Models of Inherited ALS”, Molecular Therapy, vol. 21 no. 12, pgs. 2148-2159, Dec. 2013) and Pokrishevsky et al. (“Aberrant Localization of FUS and TDP43 Is Associated with Misfolding of SOD1 in Amyotrophic Lateral Sclerosis”, Plos One, April 2012, vol. 7, issue 4, E35050, pgs. 1-9).
Meyer and Foust have been discussed in the above rejection. However, the references do not teach the elected species (a) glial cell, (b) TDP43, and (c) amyotrophic lateral sclerosis.
With respect to claims 1 and 22, Pokrishevsky teaches clinically indistinguishable ALS can be caused by genetic mutations of Cu/Zn superoxide dismutase (SOD1), TAR-DNA binding protein 43 (TDP43), or fused in scarcoma/translocated in liposarcoma (FUS/TLS), or can occur in the absence of known mutation as sporadic disease (see abstract background). Pokrishevsky teaches that motor axons from FUS-FALS and wtTDP43-SALS patient spinal cords are immunoreactive for misfolded SOD1 by immunohistochemistry with SOD1 misfolding-specific mAbs and using these same antibodies we found that transfection-driven expression of cytosolic mutants of FUS or TDP43 in vitro is associated with SOD1 misfolding by immunocytochemistry and immunoprecipitation (see pg. 5, left col. para. 1 of Discussion). Pokrishevsky teaches cytoplasmic accumulation of wtTDP43, as a local response to injury or cell stress, may also induce a productive template of misfolded SOD1, or may be a toxic consequence of SOD1 misfolding (see pg. 6, right col., para. 1).
Thus, it would have been obvious to have used the method of using fibroblasts to induce neuronal progenitor cells and subsequent differentiation into astrocytes as taught by Meyer with TDP43 as taught by Pokrishevsky because Meyer has cocultured astrocytes with mutation in SOD1 and Pokrishevsky teaches that (1) cytoplasmic accumulation of wtTDP43, as a local response to injury or cell stress, may also induce a productive template of misfolded SOD1 and (2) SOD1 misfolding-specific mAbs were used against cytosolic mutants of FUS or TDP43 in vitro is associated with SOD1 misfolding by immunocytochemistry and immunoprecipitation.
The person would have a reasonable expectation of success because it has been well understood by Pokrishevsky that SOD1 and TDP43 are correlated and connected to ALS.
With respect to 4, Meyer teaches adult human fibroblasts from living ALS patients to induced neuronal progenitor cells and subsequent differentiation into astrocytes (i-astrocytes) (see abstract and Fig. 1).
With respect to claim 5, Meyer teaches adult human fibroblasts from living ALS patients to induced neuronal progenitor cells and subsequent differentiation into astrocytes (i-astrocytes) (see abstract and Fig. 1).
With respect to claim 6, Meyer teaches direct conversion of human skin fibroblasts to tripotent iNPCs (see Fig. 1 and caption).
With respect to claim 7, Meyer teaches that astrocytes carrying C9ORF72 expansion mutation also display toxicity toward MNs and mounting evidence for that involvement of misfolded SOD1 in sporadic ALS (see pg. 832, para. 1 of Discussion).
With respect to claim 8, Meyer teaches that astrocytes carrying C9ORF72 expansion mutation also display toxicity toward MNs and mounting evidence for that involvement of misfolded SOD1 in sporadic ALS (see pg. 832, para. 1 of Discussion and abstract). Thus, the wild-types C9ORF72 and SOD1 would decrease.
With respect to claim 9, Meyer teaches ALS (see abstract).
With respect to claim 10, Meyer teaches SOD1 and C9ORF72 would read on in vitro motor neuron toxicity (abstract).
With respect to claim 11, Meyer teaches ALS, SOD1 and C9ORF72 (abstract).
With respect to claim 18, Meyer teaches direct conversion of human skin fibroblasts to tripotent iNPCs (see Fig. 1 and caption).
With respect to claims 19-20, Meyer teaches adult human fibroblasts from living ALS patients to induced neuronal progenitor cells and subsequent differentiation into astrocytes (i-astrocytes) (see abstract and Fig. 1). Meyer teaches direct conversion of human skin fibroblasts to tripotent iNPCs (see Fig. 1 and caption).
With respect to claim 21, Meyer teaches ALS (see abstract).
With respect to claim 22, Meyer teaches mutations in SOD1 and C9ORF72 (abstract).
Conclusion
No claim is allowed.
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/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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