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. Application Status This action is written in response to applicant’s correspondence received on 5/24/2024. Claims 1-3, 11, 13-15, 22-29, 32-33, 36, and 41-42 are pending. Claims 4-10, 12, 16-21, 30-31, 34-35, 37-40, and 43-45 have been previously cancelled. All pending claims are currently under examination. Nucleotide and/or Amino Acid Sequence Disclosures REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES Items 1) and 2) provide general guidance related to requirements for sequence disclosures. 37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted: In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying: the name of the ASCII text file; ii) the date of creation; and iii) the size of the ASCII text file in bytes; In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying: the name of the ASCII text file; the date of creation; and the size of the ASCII text file in bytes; In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended). When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824. If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical. If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical. Specific deficiencies and the required response to this Office Action are as follows: Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above. Required response – Applicant must provide: A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of: A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); A copy of the amended specification without markings (clean version); and A statement that the substitute specification contains no new matter. 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 appl icant regards as his invention. Claims 2, 13-14, 22-29, 32-33, 36, and 41-42 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Regarding claim 2 , claim 2 recites “the dnDLK polypeptide comprising a substitution at position 424 or 426” at line 6. However, no dnDLK polypeptide comprising a substitution at position 424 or 426 is previously recited; hence, recitation of “the dnDLK polypeptide comprising , ” emphasis added, lacks proper antecedent basis. It is recommended that line 6 be amended to recite “the dnDLK polypeptide comprises ” because it would clarify that the dnDLK in question is the polypeptide comprising at least one muta tion recited in claim 1. Note that each of the other mutant variants in claim 2 are recited as “comprises” (e.g., “the dnDLK polypeptide comprises a D or E at position 43,” line 3 of claim 2) with the exception of line 6, which recites “comprising,” which alters the subject of the claim to mean “the” dnDLK mutant , where said dnDLK mutant was not previously recited (i.e., lacks proper antecedent basis). Regarding claim 13, claim 13 recites “a leucine zipper polypeptide that inhibits homodimerization and DLK heterodimerization with (LZK).” This claim language is unclear because 1) “LZK” is a parenthetical statement, and it is unclear if this is meant to be exemplary or if it is meant to be what DLK is inhibited from forming a heterodimer with, and 2) the phrase “with (LZK)” is in general unclear, as it is unclear what heterodimer the leucine zipper polypeptide is meant to inhibit because the phrase “the (LZK)” does not clarify a subject (i.e., is it inhibition of heterodimerization with LKZ? What is the purpose of putting LZK in parentheses?). Thus, the function of the recited leucine polypeptide is generally unclear in claim 13. Claims 13, 22-29, 32-33, 36, and 41-42 ultimately depend from claim 13 and do not resolve this 112(b) issue and are therefore rejected. 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 13-14 , 28 , 29, and 32 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. Regarding claim 13, claim 13 recites a nucleic acid encoding a polypeptide, where the polypeptide is broadly recited to comprise SEQ ID NO: 8. Claim 13 therefore broadly encompasses a nucleic acid encoding a polypeptide comprising SEQ ID NO: 8. As evidenced by NCBI KAL0600635 (NCBI Accession number KAL0600635 , depicting the naturally occurring sequence of MAPK3K13 , published 1/7/2024 ), instant SEQ ID NO: 8 is a 100% match for the naturally occurring MAPK313 protein of P. cupreus (see alignment, below, SEQ ID NO: 8 top, KAL0600635 bottom, and pages 1-2 of NCBI KAL0600635): Thus, SEQ ID NO: 8 is a naturally occurring product of nature, as it is a naturally occurring amino acid sequence (Step 1A, prong 1 of the Subject Matter Eligibility Test, MPEP 2106). Regarding Step 1A, prong 2, claim 13 is broadly drawn to a nucleic acid encoding such a polypeptide as NCBI KAL0600635; as KAL0600635 is part of a naturally occurring organism, it is reasonabl e that such a protein is encoded in a nucleic acid within the genome , thus, the nucleic acid recited in claim 13 is drawn to a naturally occurring part of the P. cupreus genome encoding the protein KAL0600635. Claim 13 does not recite additional limitations which render markedly different characteristics onto the claim (Step 2A, prong 2) or transform the claim into significantly more than the judicial exception (Step 2B). Claim 13 is therefore not subject matter eligible. Regarding claim 14, claim 14 can broadly be interpreted to be a portion of a nucleic acid sequence encoding NCBI KAL0600635, where such a portion of a naturally occurring nucleic acid sequence encodes an amino acid sequence comprising 150 or fewer residues of NCBI KAL0600635 which read on SEQ ID NO: 8. As MPEP recites: “ In Myriad, the Supreme Court made clear that not all changes in characteristics will rise to the level of a marked difference, e.g., the incidental changes resulting from isolation of a gene sequence are not enough to make the isolated gene markedly different. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. The patentee in Myriad had discovered the location of the BRCA1 and BRCA2 genes in the human genome, and isolated them, i.e., separated those specific genes from the rest of the chromosome on which they exist in nature. As a result of their isolation, the isolated genes had a different structural characteristic than the natural genes, i.e. , the natural genes had covalent bonds on their ends that connected them to the rest of the chromosome, but the isolated genes lacked these bonds. However, the claimed genes were otherwise structurally identical to the natural genes, e.g., they had the same genetic structure and nucleotide sequence as the BRCA genes in nature ,” MPEP 2106.04(C), IIC. Thus, the mere fact that the nucleic acid encoding the presently recited portion of SEQ ID NO: 8 is shorter than the full-length sequence of the gene is irrelevant, as the nucleic acid sequence is a naturally occurring part of the P. cupreus genome. Thus, claim 14 does not recite markedly different characteristics or any additional elements which would transform the claim into significantly more than the judicial exception of the claim (i.e., a naturally occurring nucleic acid sequence in P. cupreus ). Claim 14 is therefore not subject matter eligible. Regarding claim 28, NCBI KAL0600635 teaches that SEQ ID NO: 8 is naturally encoded within the genome of P. cupreus , and therefore teaches that the nucleic acid is within a “host cell.” Claim 28 does not recite any additional limitations which would integrate the judicial exception into a practical application (Step 2A, prong 2) or transform the claim into significantly more (Step 2B). Claim 28 is therefore not subject matter eligible. Regarding claims 29 and 32, the specification identifies SEQ ID NO: 8 as being simply the sequence of human LZK zipper domain (e.g., page 49). Thus, claims 29 and 32 are drawn to naturally occurring human cells comprising SEQ ID NO: 8, as these claims depend from claim 13 which broadly encompasses a nucleic acid encoding a polypeptide comprising SEQ ID NO: 8, which reasonably includes a full-length LZK. Thus, claims 29 and 32 are directed to naturally occurring human cells and do not recite any additional limitations which would either 1) integrate the judicial exceptions into a practical application (Step 2A, prong 2) or 2) transform the claim into significantly more than the judicial exception (Step 2B). Claims 29 and 32 are therefore not subject matter eligible. 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, 11, 13-15, 22-29, 32-33, 36, and 41-42 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. MPEP 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”. For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Regents of the University of California v. Eli Lilly & Co, 119 F.3d at 1568, 43 USPQ2d at 1406 . Regarding independent claims 1 and 13, these claims are drawn to genera of nucleic acids encoding polypeptides including a genus of polypeptide that is at least 80% identical to SEQ ID NO: 1 (claim 1 and its dependent claims) or SEQ ID NO: 8 (claim 13 and its dependent claims). Hence, the claims are broadly drawn to genera of amino acid sequences and the nucleic acids which encode them, where the amino acid sequences have up to 20% divergence from either SEQ ID NO: 1 or SEQ ID NO:8. This claim language is problematic because the specification has not shown a sufficient number of species to show possession of these broad, unpredictable genera of amino acid sequences, where each genus of sequences can comprise up to 20% mutations. Furthermore, claim 1 recites specific functionality of the polypeptide: that it functions as a dominant negative mutant variant of DLK in claim 1 , while claim 13 recites that the polypeptide functions to inhibit hetero/homodimerization. Thus, the claims recite functional limitations. However, no core structural elements are identified in either SEQ ID NOs 1 or 8 to confer such functionality. Thus, the broad genera of polypeptide sequences and their variants as recited were not shown to be in possession by the Applicant at the time of filing. Regarding the guidance provided in the specification, the Applicant provides examples, methods, and assays beginning at page 40 of the specification. The specification recites that random mutagenesis of DLK was performed (page 41 final paragraph to page 42 first paragraph). However, no data is presented to accompany any results of random mutagenesis; hence, no critical domains or residues are identified with any specific functionality by the Applicant with the exception of a few tested. For instance, the Applicants tested and reduced to practice the S302A mutation and compared the results to the K185A mutant, where the S302A mutant was found to show protective characteristics (paragraphs 179-181 and Figure 2 ). Furthermore, the K185 and S302 mutants showed variability in their functionality (see Figure 2); thus, mutations at different residues showed variable, unpredictable results according the data provided in the specification. Furthermore, regarding mutations to DLK, the specification appears to recite that some predicted sites showed no significant variation in neuroprotective functionality (see paragraph 189). Thus, the specification does not appear to teach core structural elements or a specific mutational strategy to characterize the broad genus recited, as different mutations have different and unpredictable effects on the functionality of the protein (paragraph 189). Paragraph 191 recites that a random mutagenesis strategy was employed to identify the mutant G516V, however such a mutant variant does not appear to have been tested or verified with any specific functionality , nor does the random mutagenesis appear to characterize the DLK protein . Furthermore, no mutagenesis analysis and/or characterization of SEQ ID NO: 8 or the nucleic acid encoding the polypeptide SEQ ID NO: 8 (i.e., LZK) appears to have been performed. Thus, the Applicant has not shown possession of the recited variants of either SEQ ID NO: 1 or 8. Regarding the state of the art, proteins which are phosphorylated such as DLK are known to be uncharacterized and unpredictable, where such proteins are involved with highly complex signaling networks. For instance, Jaskula -Ranga ( WO 2018/009562 A 1) is a patent document that focuses on methods of using CRISPR to treat retinal degeneration disease (Title, Abstract, throughout). Jaskula -Ranga teaches that: “ in vertebrates, there are several DLK phosphorylation sites, including S643, S302, S295, S302, T306 and S643 which do not appear to be regulated by the known DLK kinases (i.e. JNK and DLK), suggesting the possibility of novel, upstream regulatory kinases ,” (page 132, first paragraph). Thus, Jaskula -Ranga teaches that phosphorylation sites are not all characterized fully, and further that DLK proteins are known to be regulated by unknown DLK kinases (above). Jaskula -Ranga therefore teaches that phosphorylation sites on DLK proteins are not fully characterized or known, and that changing such sites would therefore have unknown effects, as kinases which act on such DLKs are also unknown (above). Furthermore , Jin ( Jin Y et al. Annu Rev Cell Dev Biol. 2019 Oct 6;35:501-521 ) is a review article focused on DLK kinases (Title, Abstract, and throughout) . Jin teaches that: The DLK proteins are represented by two members known as MAP3K12 (or DLK) and MAP3K13 (or LZK) in vertebrate genomes and by a single member in most invertebrates (Figure 1). Each full-length kinase consists of approximately 900 amino acids, with the kinase domain at the N terminus, followed by two LZs and a long C terminus. The sequence homology among all members is primarily in the kinase and LZ domains, while the C termini are rich in proline, serine, and acidic amino acids but share little sequence similarity between DLK and LZK in the same species (Figure 1). LZ domains are found in many proteins and generally mediate homo- or heterodimerization. For DLK and LZK, the LZ domains are essential for their activation; mutating a single leucine residue in either LZ abolishes the activity of these kinases to phosphorylate JNK in transfected cell lines ,” (page 2, third paragraph). Thus, Jin teaches that individual point mutations are known to have dramatic effects on the functionality of both DLK and LZK kinases (above). Given the fact that the Applicant’s specification itself shows a diverse range of unpredictable results concerning individual mutations in the recited protein sequences (e.g., Figure 2, paragraph 189), and furthermore their recited random mutagenesis strategy does not show functional data or a way to predict what mutations may have any functional effects as either creating a dominant negative DLK (claim 1) or inhibitory LZK (claim 13), the Applicant does not appear to have characterized the presently recited genera of polypeptides comprising 80% sequence identity to either SEQ ID NOs 1 or 8. Claims 2-3, 11, and 15, depend from claim 1 and claims 14, 22-29, 32-33, 36, and 41-42 depend from claim 13; these claim do not resolve the 112a issue and are therefore also rejected. Regarding claim 15, although claim 15 narrows the genus of SEQ ID NO: 1 to be 90% identical, such a genus is still a large, uncharacterized, and unpredictable of DLK mutations as discussed above. Claim 15 is therefore also rejected because the Applicant has not shown sufficient species to show that they have fully characterized DLKs comprising up to 10% mutation to SEQ ID NO: 1. Furthermore, method claims 33, 36, 41, and 42 recite additional limitations with functional requirements. For instance, claims 33 and 41 recite methods of inhibiting neural cell death (claim 33) or treating or preventing neural cell death (claim 41). Given that the genus of polypeptide recited in these claims itself has not been characterized (i.e., SEQ ID NO: 8), the number of mutants and variants comprised within this genus and their role in treating or preventing or inhibiting neural cell death has also not been characterized. Claim Rejections - 35 USC § 102 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. (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 13-14, 22-29, 32-33, 36, and 41-42 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Chalberg (WO 2020/168111 A1, published 8/20/2020). Regarding claim 13, Chalberg teaches SEQ ID NO: 4, shown in alignment with instant SEQ ID NO: 8 (DLK zipper, see Table 1, page 17 of Chalberg ), below: SEQ ID NO: 4 of Chalberg (top) aligned with instant SEQ ID NO: 8 (bottom). Thus, when aligned with SEQ ID NO: 8, SEQ ID NO: 4 of Chalberg shows 81% sequence identity with instant SEQ ID NO: 8. Per the instant specification: “ The terms "identical" or "percent identity," in the context of two or more polypeptide or polynucleotide sequences, refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acids or nucleotides that are the same (e.g., at least 70%, at least 75%, at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher) identity over a specified region, when compared and aligned for maximum correspondence over a comparison window or designated region as measure by manual alignment and visual inspection or using a BLAST ,” (paragraph 22 of the specification) Thus, SEQ ID NO: 4 of Chalberg reads on at least 80% identity to instant SEQ ID NO: 8, per the definition recited in the instant specification of “percent identity . ” Furthermore, Chalberg also teaches SEQ ID NO: 11 (Table 1, page 18), which is shown in alignment below to show 100% identity to instant SEQ ID NO: 8: Instant SEQ ID NO: 8 aligned with SEQ ID NO: 11 of Chalberg , where the alignment shows 100% identity of a region/subregion of SEQ ID NO: 8. Thus, SEQ ID NO: 11 of Chalberg also reads on instantly recited SEQ ID NO: 8 because a specified region or subregion (i.e., “percent identity,” as defined in the instant specification at paragraph 22) of SEQ ID NO: 11 of Chalberg is 100% identical to instant SEQ ID NO: 8. Thus, Chalberg anticipates the recited structure of claim 13, and therefore further anticipates its inherent properties (e.g., “inhibits homodimerization” also see paragraph 86 which teaches inhibitory domains of SEQ ID NO: 4). Regarding claim 14, both of SEQ ID NOs 4 and 11 of Chalberg are fewer than 150 residues. Regarding claims 22-26, Chalberg teaches that the sequence can be comprised in a rAAV vector (e.g., paragraphs 91), where furthermore the vector can be AAV2.7m8 (paragraph 94). Regarding claim 27, Chalberg teaches that the expression cassette in vectors can comprise WPRE ( Table 2, page 19, final row). Regarding claims 28-29, Chalberg teaches that that the vectors of their invention can be introduced into a retinal ganglion (e.g., paragraph 97). Regarding claim 32, Chalberg teaches that the vectors are introduced into retinal ganglions to treat disease (paragraph 98), where furthermore “administration” is taught to be in human cells (paragraph 22). Thus, Chalberg anticipates claim 32 by teaching that such vectors are administered into retinal ganglions (paragraph 98). Regarding claim s 33, 36, 41, Chalberg teaches a method of treatment of retinal ganglion cells by administration of the vectors of their invention and therefore anticipates the active steps of the methods recited in claims 33, 36, and 41 (paragraphs 97-98). Regarding claim 42, Chalberg teaches that the subject can have glaucoma (paragraph 97). Claim Rejections - 35 USC § 103 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. 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 1- 3 , 11, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Borchers ( Börchers S et al. Naunyn Schmiedebergs Arch Pharmacol . 2017 Aug;390(8):813-825) in view of GenBank NP_001180440 (‘440, GenBank Accession number of locus NP_001180440, Human MAP 3 K12 sequence, published 6/25/2017) and Chen ( Chen X et al. J Neurosci . 2008 Jan 16;28(3):672-80 ). Regarding claim s 1 -2 , Borchers is a research article focused on the study of the DLK kinase in HIT-T15 cells (Title, Abstract, and throughout). As an initial matter, the presently recited SEQ ID NO: 1 is the human DLK protein (see specification at page 47). Thus, claim 1 is broadly reciting a huma n DLK protein comprising a mutation at position 302. Borchers teaches the wildtype DLK protein, and furthermore teaches the mutation at position 302, where the mutation is S302A (e.g., page 815 left column, first paragraph, Figure 2). Borchers teaches that such DLK S302A mutants can be encoded in nucleic acids which encode the polypeptides (for instance, page 814, right column, final paragraph into page 815, left column, first paragraph). Furthermore, Borchers teaches that: “ These data suggest that TNFα induces beta-cell apoptosis through activation of DLK thereby inhibiting the beta-cell protective transcription factor CREB. Furthermore, activation of DLK by a well-known diabetic risk factor supports the role of DLK in the pathogenesis of diabetes mellitus. Thus, the inhibition of DLK might prevent or retard the pathogenesis of diabetes mellitus type 2 ,” (Abstract). Thus, Borchers teaches a motivation to inhibit DLK for treatment of disease, and further teaches that it is an important drug target ( above, and also “ Discussion, ” first paragraph). Borchers further teaches that: “ These findings indicate that TNFα leads to a sustained activation of JNK and DLK; whereby DLK stimulates JNK, JNK activity promotes DLK dimerization and activation which in turn increases JNK activity . Thus, the interruption of this cycle might constitute a worthwhile drug target ,” (page 822, right column, first paragraph) Furthermore, when Borchers teaches that DLK is an important drug target, they reference Chen (Discussion, first paragraph). Thus, Chen can be viewed as part of the teachings of Borchers. Chen is a research article which teaches the antiapoptotic and trophic effects of dominant negative DLK mutants in dopamine neurons (Title, Abstract, and throughout). Thus, Borchers teaches the therapeutic potential of DLK and references Chen who teaches such therapeutic potential in the form of dominant negative DLK. Borchers furthermore teaches the dominant negative S302A form of DLK, and further teaches DLK role in disease and the benefit of targeting it for treatment (Abstract, Discussion first paragraph) . Borchers, by referencing Chen and teaching / suggesting DLK as a target disease, and by teaching the dominant negative form of DLK S302, teaches the essential subject matter of claim 1 (i.e., a dnDLK that has a mutation at position 302) . However, Borcher does not appear to explicitly teach the sequence of human DLK. GenBank ‘440 is sequence data from GenBank which teaches the sequence of human MAP3K12. ‘440 teaches that MAP3K12 is a synonym for DLK (see “Remark” section on page 1 of ‘440). Thus, ‘440 teaches the sequence of the human DLK sequence. An alignment of ‘440 and instant SEQ ID NO: 1 is shown below: SEQ ID NO: 1 (TOP) aligned with ‘440 (Bottom). Thus, SEQ ID NO: 1 and ‘440 are a 100% identical match, where position 302 is the serine site taught by Borchers. It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to make a mutated version of ‘440 comprising the mutation S302A because Borchers has in fact already taught this mutation and its potential role in therapeutics. Borchers simply did not explicitly teach the human sequence of the protein DLK, but the sequence was already known in the art as taught by ‘440. Thus, Borchers in light of the teachings of ‘440 arrive at the present invention, where the S302A mutation was already known in the art and taught by Borchers. Furthermore, a practitioner would be motivated to make such a mutation in human DLK because Borcher/Chen teach that such mutations are useful for therapeutics against disease, where Chen further teaches that dominant negative DLK mutants have therapeutic benefits (Abstract). Regarding claim 3, Chen teaches methods of packaging shortened domains of the DLK leucine zipper protein (e.g., page 673, left column, third paragraph, “ domain of human DLK was obtained by PCR from the human DLK clone using primers for the nucleotide sequence encoding amino acids 372–487 ”). Thus, the methods of Chen involving packaging leucine zipper domains into AAV vectors includes shorter regions of such proteins. Given that Chen has already taught methods of truncation of such DLK proteins by domain, and Borchers teaches the 302 region (i.e., the N-terminal region comprised by the instantly recited region of 1-520 in claim 1), it would be obvious to a practitioner of ordinary skill in the art to truncate such a protein region, as Chen has already taught and reduced such a product to practice (Chen, page 673, left column, third paragraph). Thus, a practitioner could arrive at constructs as short as 550 amino acids, as Chen has already taught that shorter constructs have been made and reduced to practice for dominant negative effects (i.e., residues “ 372-487, ” page 673, left column, third paragraph, where the inclusion of additional residues to include the 302A mutation of Borchers , for instance, residues 302-487 , would reasonably be expected to function given that shorter versions of the protein were already known to function as dominant negative DLKs, per Chen). Regarding claim 11, an alignment of SEQ ID NO: 6 with ‘440 is given below: SEQ ID NO: 6 (top) aligned with ‘440 (bottom). As seen above, SEQ ID NO: 6 and ‘440 are a ~99% match with the exception that SEQ ID NO: 6 comprises the S302A mutation. Thus, the S302A DLK mutant rendered obvious by the combination of Borchers/’440 discussed in the rejection of claim 1 also reads on claim 11, where the Borchers/’440 S302A DLK mutant would comprise SEQ ID NO: 6. Regarding claim 15, as discussed above, the S302A DLK mutant rendered obvious by Borchers/’440 is a 100% match of SEQ ID NO: 1 comprising a mutation at S302 (see rejection of claim 1, above). Thus, the mutant DLK S302 variant rendered obvious by Borchers/’440 also reads on claim 15 because residues 158-520 of the Borchers/’440 DLK polypeptide are at least a 90% match to SEQ ID NO: 1. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT DOUGLAS CHARLES RYAN whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-8406 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 8AM - 5PM . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT Ram Shukla can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571)-272-0735 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /D.C.R./ Examiner, Art Unit 1635 /KIMBERLY CHONG/ Primary Examiner, Art Unit 1636