Single nucleic acid vector compositions, kits and their uses in the treatment of clrn1 associated hearing loss and / or vision loss

Description

[0001] This application claims priority for the Patent Application US Provisional Serial No. 62 / 689,660, filed June 25, 2018; the entire contents of which are incorporated herein by reference. TECHNICAL FIELD

[0002] The present invention relates generally to the use of nucleic acids to treat hearing loss, vision loss, or both in a human individual. BACKGROUND OF THE INVENTION

[0003] Current treatments for hearing loss consist mainly of hearing aids for mild to severe hearing loss and cochlear implants for severe to profound hearing loss; however, a long-felt need for agents and methods to prevent or reverse syndromic deafness remains.

[0004] Hearing loss can be conductive (resulting from the ear canal or middle ear), sensorineural (resulting from the inner ear or auditory nerve), or mixed. Most forms of syndromic deafness are associated with permanent hearing loss caused by damage to the structures of the inner ear (sensorineural deafness), although some forms may involve changes in the middle ear (conductive hearing loss). The vast majority of human sensorineural hearing loss is caused by abnormalities in the hair cells of the organ of Corti in the cochlea (hair cell malfunction). Hair cells may be abnormal at birth or may be damaged during an individual's life (for example, as a result of Petition 870260061675, dated 06 / 23 / 2026, page 9 / 935 2 / 362 sound trauma or infection). SUMMARY

[0005] The present invention relates to a composition including at least two different nucleic acid vectors, wherein each of the at least two different vectors includes a coding sequence encoding a different portion of a CLRN1 protein, which can be used to generate a sequence encoding an active CLRN1 protein (e.g., a complete CLRN1 protein) in a mammalian cell and thus treat CLRN1-associated hearing loss and / or vision loss in an individual in need of such treatment. The invention also relates to compositions including a single nucleic acid vector that includes a coding sequence for a first and / or second isoform of the CLRN1 protein.

[0006] Compositions comprising at least two different nucleic acid vectors are provided in this document, wherein: each of the at least two different vectors includes a coding sequence that encodes a different portion of a CLRN1 protein, each of the encoded portions being at least 30 amino acid residues in length, wherein the amino acid sequence of each of the encoded portions may optionally partially overlap with the amino acid sequence of a different encoded portion; no single vector of the at least two different vectors encodes a complete CLRN1 protein; at least one of the coding sequences includes a nucleotide sequence spanning two consecutive exons of CLRN1 genomic DNA and does not have an intronic sequence between the two consecutive exons;When introduced into a mammalian cell, the at least two different vectors undergo homologous recombination with each other, thus forming a recombined nucleic acid that encodes a complete CLRN1 protein. In some embodiments of either; Petition 870260061675, dated 06 / 23 / 2026, page 10 / 935 3 / 362 In one of the compositions provided in this document, each of at least two different vectors includes a coding sequence that encodes a different portion of a first isoform of the CLRN1 protein. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein consists of SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, one of at least two different nucleic acid vectors further includes a sequence that encodes a second isoform of the CLRN1 protein.In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 5. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes SEQ ID NO: 5. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein consists of SEQ ID NO: 5. In some embodiments of any of the compositions provided in this document, each of at least two different vectors includes a coding sequence that encodes a different portion of a second isoform of the CLRN1 protein. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 5.In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes a. Petition 870260061675, dated 06 / 23 / 2026, p. 11 / 935 4 / 362 SEQ ID NO: 5. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein consists of SEQ ID NO: 5. In some embodiments of any of the compositions provided in this document, one of at least two different nucleic acid vectors further includes a sequence encoding a first isoform of the CLRN1 protein. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein consists of SEQ ID NO: 3.

[0007] In some embodiments of any of the compositions provided in this document, at least one of the two different vectors includes a 5' untranslated region (UTR), a 3' UTR, or both. In some embodiments of any of the compositions provided in this document, the 5' UTR comprises at least 10 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 20 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 50 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 80 contiguous nucleotides from anywhere within SEQ ID NO: 12.In some versions of any of the compositions provided in this document, the 5' UTR includes a se. Petition 870260061675, dated 06 / 23 / 2026, p. 12 / 935 5 / 362 sequence that is at least 80% identical to SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 10 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 20 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 50 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 80 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes a sequence which is at least 80% identical to SEQ ID NO: 15.

[0008] In some embodiments of any of the compositions provided in this document, each of at least two different vectors is a plasmid, a transposon, a cosmid, an artificial chromosome, or a viral vector. In some embodiments of any of the compositions provided in this document, each of at least two different vectors is a human artificial chromosome (HAC), a yeast artificial chromosome (YAC), a bacterial artificial chromosome (BAC), or a P1-derived artificial chromosome (PAC). In some embodiments of any of the compositions provided in this document, each of at least two different vectors is a viral vector selected from an adeno-associated virus (AAV) vector, an adenovirus vector, a lentivirus vector, or a retrovirus vector. In some embodiments of any of the compositions provided in this document, each of at least two different vectors is an AAV vector. Petition 870260061675, dated 06 / 23 / 2026, p. 13 / 935 6 / 362

[0009] In some embodiments of any of the compositions provided in this document, the amino acid sequence of none of the encoded portions overlaps with the amino acid sequence of a different encoded portion. In some embodiments of any of the compositions provided in this document, the amino acid sequence of each of the encoded portions partially overlaps with the amino acid sequence of a different encoded portion. In some embodiments of any of the compositions provided in this document, the overlapping amino acid sequence is from about 30 amino acid residues to about 202 amino acid residues in length.In some embodiments of any of the compositions provided in this document, the vectors include two different vectors, each of which includes a different segment of an intron, wherein the intron includes the nucleotide sequence of an intron that is present in the genomic DNA of CLRN1 and wherein two different intron segments overlap in sequence by at least 100 nucleotides. In some embodiments of any of the compositions provided in this document, the two different intron segments overlap in sequence by from 100 nucleotides to about 800 nucleotides.

[0010] In some embodiments of any of the compositions provided in this document, the entire nucleotide sequence of each of at least two different vectors is from about 500 nucleotides to about 10,000 nucleotides in length. In some embodiments of any of the compositions provided in this document, the entire nucleotide sequence of each of at least two different vectors is from 500 nucleotides to 5,000 nucleotides in length. In some embodiments of any of the compositions provided in this document, the number of different vectors in the composition is two. In some embodiments of Petition 870260061675, dated 06 / 23 / 2026, page 14 / 935 7 / 362 In any of the compositions provided in this document, a first of two different vectors includes a coding sequence that encodes an N-terminal portion of the CLRN1 protein. In some embodiments of any of the compositions provided in this document, the N-terminal portion of the CLRN1 protein is between 30 and 202 amino acids in length. In some embodiments of any of the compositions provided in this document, the N-terminal portion of the CLRN1 protein is between 60 and 170 amino acids in length. In some embodiments of any of the compositions provided in this document, the first vector further includes a 5' UTR sequence. In some embodiments of any of the compositions provided in this document, the 5' UTR comprises at least 10 contiguous nucleotides from anywhere within SEQ ID NO: 12.In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 20 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 50 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 80 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes a sequence that is at least 80% identical to SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the first vector further includes one or both of a promoter and a Kozak sequence.In some embodiments of any of the compositions provided in this document, the first vector includes a promoter that is either an inducible promoter, a constitutive promoter, or a woven promoter. Petition 870260061675, dated 06 / 23 / 2026, p. 15 / 935 8 / 362 specific. In some embodiments of any of the compositions provided in this document, the second of the two different vectors includes a coding sequence that encodes a C-terminal portion of the CLRN1 protein. In some embodiments of any of the compositions provided in this document, the C-terminal portion of the CLRN1 protein is between 30 and 202 amino acids in length. In some embodiments of any of the compositions provided in this document, the C-terminal portion of the CLRN1 protein is between 60 and 170 amino acids in length. In some embodiments of any of the compositions provided in this document, the second vector also includes a polyadenylation signal sequence. In some embodiments of any of the compositions provided in this document, the second vector also includes a 3' UTR sequence.In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 10 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 20 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 50 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 80 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes a sequence that is at least 80% identical to SEQ ID NO: 15.

[0011] Also provided in this document are compositions that include a single nucleic acid vector, wherein the vector includes Petition 870260061675, dated 06 / 23 / 2026, page 16 / 935 9 / 362 one or both of (i) a first coding sequence encoding a first isoform of the CLRN1 protein and (ii) a second coding sequence encoding a second isoform of the CLRN1 protein, wherein one or both of the first and second coding sequences include a nucleotide sequence spanning two consecutive exons of CLRN1 genomic DNA and without an intronic sequence between the two consecutive introns. In some embodiments of any of the compositions provided in this document, the single nucleic acid vector contains the first coding sequence, and not the second coding sequence. In some embodiments of any of the compositions provided in this document, the single nucleic acid vector contains the second coding sequence, and not the first coding sequence.In some embodiments of any of the compositions provided in this document, the single nucleic acid vector contains both the first coding sequence and the second coding sequence. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein consists of SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 5.In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes SEQ ID NO: 5. In some embodiments of any of the compositions provided in this document, a. Petition 870260061675, dated 06 / 23 / 2026, p. 17 / 935 10 / 362 second isoform of the CLRN1 protein consists of SEQ ID NO: 5.

[0012] In some embodiments of any of the compositions provided in this document, the single nucleic acid vector further includes a 5' untranslated region (UTR), a 3' UTR, or both. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 10 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 20 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 50 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 80 contiguous nucleotides from anywhere within SEQ ID NO: 12.In some embodiments of any of the compositions provided in this document, the 5' UTR includes a sequence that is at least 80% identical to SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 10 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 20 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 50 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 80 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, at 3' UTR. Petition 870260061675, dated 06 / 23 / 2026, p. 18 / 935 11 / 362 includes a sequence that is at least 80% identical to SEQ ID NO: 15.

[0013] In some embodiments of any of the compositions provided in this document, the single nucleic acid vector is a plasmid, a transposon, a cosmid, an artificial chromosome, or a viral vector. In some embodiments of any of the compositions provided in this document, the single nucleic acid vector is a human artificial chromosome (HAC), a yeast artificial chromosome (YAC), a bacterial artificial chromosome (BAC), or a P1-derived artificial chromosome (PAC). In some embodiments of any of the compositions provided in this document, the single nucleic acid vector is a viral vector selected from an adeno-associated virus (AAV) vector, an adenovirus vector, a lentivirus vector, or a retrovirus vector. In some embodiments of any of the compositions provided in this document, the single nucleic acid vector is an AAV vector.In some embodiments of any of the compositions provided in this document, the single nucleic acid vector further includes one or both of a promoter and a Kozak sequence. In some embodiments of any of the compositions provided in this document, the first vector includes a promoter that is an inducible promoter, a constitutive promoter, or a tissue-specific promoter. In some embodiments of any of the compositions provided in this document, the single nucleic acid vector further includes a polyadenylation signal sequence. Some embodiments of any of the compositions provided in this document further include a pharmaceutically acceptable excipient.

[0014] Kits that include any of the compositions provided in this document are also provided in this document. Some embodiments of any of the kits provided in this document are Petition 870260061675, dated 06 / 23 / 2026, p. 19 / 935 12 / 362 also include a pre-filled syringe that includes or contains any of the compositions described in this document.

[0015] Methods are also provided in this document that involve introducing into the cochlea of ​​a mammal a therapeutically effective amount of any of the compositions provided in this document. In some embodiments of any of the methods provided in this document, the mammal is a human. In some embodiments of any of the compositions provided in this document, the mammal has been previously identified as having a defective CLRN1 gene.

[0016] Methods for increasing the expression of a complete CLRN1 protein in a mammalian cell are also provided in this document, including the introduction of any of the compositions provided in this document into the mammalian cell. In some embodiments of any of the methods provided in this document, the mammalian cell is an inner hair cell of the cochlea or an outer hair cell of the cochlea. In some embodiments of any of the methods provided in this document, the mammalian cell is a retinal cell. In some embodiments of any of the methods provided in this document, the mammalian cell is a human cell. In some embodiments of any of the methods provided in this document, it has been previously determined that the mammalian cell possesses a defective CLRN1 gene.

[0017] This document also provides methods for increasing the expression of a CLRN1 protein in an inner hair cell, an outer hair cell, or both in a mammalian cochlea, including: introducing a therapeutically effective amount of any of the compositions provided in this document into the mammalian cochlea. This document also provides Petition 870260061675, dated 06 / 23 / 2026, page 20 / 935 13 / 362 methods to increase the expression of a complete CLRN1 protein in a mammalian eye that include: intraocular administration of a therapeutically effective amount of any of the compositions provided in this document into the mammalian eye. In some embodiments of any of the compositions provided in this document, the mammal has been previously identified as having a defective CLRN1 gene. In some embodiments of any of the methods provided in this document, the mammal is a human.

[0018] This document also provides methods for treating hearing loss in an individual identified as possessing a defective CLRN1 gene, including: administering a therapeutically effective amount of any of the compositions provided in this document into the individual's cochlea. This document also provides methods for treating vision loss in an individual identified as possessing a defective CLRN1 gene, including: administering a therapeutically effective amount of any of the compositions provided in this document into the individual's eye. In some embodiments of any of the methods provided in this document, the individual has Usher syndrome type III. In some embodiments of any of the methods provided in this document, the individual is a human being.Some modalities of any of the methods provided in this document also include, prior to the administration step, determining that the individual possesses a defective CLRN1 gene.

[0019] Also provided in this document are compositions that include two different nucleic acid vectors, wherein: a first nucleic acid vector of the two different nucleic acid vectors includes a promoter, a first coding sequence that encodes an N-terminal portion of a CLRN1 protein positioned Petition 870260061675, dated 06 / 23 / 2026, page 21 / 935 14 / 362 3' of the promoter and a splice donor sequence positioned at the 3' end of the first coding sequence; and a second nucleic acid vector of the two different nucleic acid vectors includes a splice acceptor sequence, a second coding sequence encoding a C-terminal portion of a CLRN1 protein positioned at the 3' end of the splice acceptor sequence, and a polyadenylation signal sequence at the 3' end of the second coding sequence; wherein each of the coding portions is at least 30 amino acid residues in length, wherein the amino acid sequences of the two coding portions do not overlap with each other; wherein no single vector of the two different vectors encodes a complete CLRN1 protein; and when introduced into a mammalian cell, splicing occurs between the splice donor sequence and the splice acceptor sequence, thus forming a recombined nucleic acid encoding a complete CLRN1 protein.In some embodiments of any of the compositions provided in this document, the first coding sequence encodes an N-terminal portion of a first isoform of the CLRN1 protein, and the second coding sequence encodes a C-terminal portion of the first isoform of the CLRN1 protein. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first nucleic acid vector of the second nucleic acid vector further includes a sequence that... Petition 870260061675, dated 06 / 23 / 2026, p. 22 / 935 15 / 362 encodes a second isoform of the CLRN1 protein. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 5. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes SEQ ID NO: 5. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein consists of SEQ ID NO: 5.

[0020] In some embodiments of any of the compositions provided in this document, the first coding sequence encodes an N-terminal portion of a second isoform of the CLRN1 protein, and the second coding sequence encodes a C-terminal portion of the second isoform of the CLRN1 protein. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 5. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes SEQ ID NO: 5. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein consists of SEQ ID NO: 5.In some embodiments of any of the compositions provided in this document, the first nucleic acid vector or the second nucleic acid vector further includes a sequence encoding a first isoform of the CLRN1 protein. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes SEQ ID NO: 3. Petition 870260061675, dated 06 / 23 / 2026, p. 23 / 935 16 / 362 some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein consists of SEQ ID NO: 3.

[0021] In some embodiments of any of the compositions provided in this document, one or both of the first nucleic acid vector and the second nucleic acid vector include a 5' untranslated region (UTR), a 3' UTR, or both. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 10 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 20 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 50 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 80 contiguous nucleotides from anywhere within SEQ ID NO: 12.In some embodiments of any of the compositions provided in this document, the 5' UTR includes a sequence that is at least 80% identical to SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 10 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 20 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 50 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR... Petition 870260061675, dated 06 / 23 / 2026, p. 24 / 935 17 / 362 includes at least 80 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes a sequence that is at least 80% identical to SEQ ID NO: 15.

[0022] In some embodiments of any of the compositions provided in this document, each of the first nucleic acid vector and second nucleic acid vector is a plasmid, a transposon, a cosmid, an artificial chromosome, or a viral vector. In some embodiments of any of the compositions provided in this document, each of the first nucleic acid vector and second nucleic acid vector is a human artificial chromosome (HAC), a yeast artificial chromosome (YAC), a bacterial artificial chromosome (BAC), or a P1-derived artificial chromosome (PAC). In some embodiments of any of the compositions provided in this document, each of the first nucleic acid vector and second nucleic acid vector is a viral vector selected from an adeno-associated virus (AAV) vector, an adenovirus vector, a lentivirus vector, or a retrovirus vector.In some embodiments of any of the compositions provided in this document, each of the first nucleic acid vector and second nucleic acid vector is an AAV vector. In some embodiments of any of the compositions provided in this document, at least one of the coding sequences includes a nucleotide sequence spanning two consecutive exons of CLRN1 genomic DNA, and without an intronic sequence between the two consecutive exons.

[0023] Also provided in this document are compositions that include two different nucleic acid vectors, wherein: a first nucleic acid vector of the two different nucleic acid vectors includes a promoter, a first coding sequence that Petition 870260061675, dated 06 / 23 / 2026, page 25 / 935 18 / 362 encodes an N-terminal portion of a CLRN1 protein positioned 3' from the promoter, a splice donor sequence positioned at the 3' end of the first coding sequence, and a first detectable marker gene positioned 3' from the splice donor sequence; and a second nucleic acid vector of the two different nucleic acid vectors includes a second detectable marker gene, a splice acceptor sequence positioned 3' from the second detectable marker gene, a second coding sequence encoding a C-terminal portion of a CLRN1 protein positioned at the 3' end of the splice acceptor sequence, and a polyadenylation signal sequence positioned at the 3' end of the second coding sequence; wherein each of the coded portions is at least 30 amino acid residues in length, wherein the amino acid sequences of the coded portions do not overlap with each other;in which no single vector of the two different vectors encodes a complete CLRN1 protein;When introduced into a mammalian cell, splicing occurs between the splice donor sequence and the splice acceptor sequence, thus forming a recombined nucleic acid that encodes a complete CLRN1 protein. In some embodiments of any of the compositions provided in this document, the first coding sequence encodes an N-terminal portion of a first isoform of the CLRN1 protein, and the second coding sequence encodes a C-terminal portion of the first isoform of the CLRN1 protein. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first isoform; Petition 870260061675, dated 06 / 23 / 2026, p. 26 / 935 19 / 362 ma of the CLRN1 protein consists of SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first nucleic acid vector of the second nucleic acid vector further includes a sequence encoding a second isoform of the CLRN1 protein. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 5. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes SEQ ID NO: 5. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein consists of SEQ ID NO: 5.In some embodiments of any of the compositions provided in this document, the first coding sequence encodes an N-terminal portion of a second isoform of the CLRN1 protein, and the second coding sequence encodes a C-terminal portion of the second isoform of the CLRN1 protein. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 5. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes SEQ ID NO: 5. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein consists of SEQ ID NO: 5.In some embodiments of any of the compositions provided in this document, the first nucleic acid vector or the second nucleic acid vector further includes a sequence encoding a first isoform of the CLRN1 protein. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes a sequence that is at least 95% identical to... Petition 870260061675, dated 06 / 23 / 2026, p. 27 / 935 20 / 362 SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein consists of SEQ ID NO: 3.

[0024] In some embodiments of any of the compositions provided in this document, one or both of the first nucleic acid vector and the second nucleic acid vector include a 5' untranslated region (UTR), a 3' UTR, or both. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 10 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 20 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 50 contiguous nucleotides from anywhere within SEQ ID NO: 12.

[0025] In some embodiments of any of the compositions provided in this document, the 5' UTR comprises at least 80 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes a sequence that is at least 80% identical to SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 10 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 20 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, Petition 870260061675, dated 06 / 23 / 2026, p. 28 / 935 21 / 362 specified in this document, the 3' UTR includes at least 50 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 80 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes a sequence that is at least 80% identical to SEQ ID NO: 15.

[0026] In some embodiments of any of the compositions provided in this document, each of the first nucleic acid vector and second nucleic acid vector is a plasmid, a transposon, a cosmid, an artificial chromosome, or a viral vector. In some embodiments of any of the compositions provided in this document, each of the first nucleic acid vector and second nucleic acid vector is a human artificial chromosome (HAC), a yeast artificial chromosome (YAC), a bacterial artificial chromosome (BAC), or a P1-derived artificial chromosome (PAC). In some embodiments of any of the compositions provided in this document, each of the first nucleic acid vector and second nucleic acid vector is a viral vector selected from an adeno-associated virus (AAV) vector, an adenovirus vector, a lentivirus vector, or a retrovirus vector.In some embodiments of any of the compositions provided in this document, each of the first nucleic acid vector and second nucleic acid vector is an AAV vector. In some embodiments of any of the compositions provided in this document, at least one of the coding sequences comprises a nucleotide sequence spanning two consecutive exons of CLRN1 genomic DNA, and without an intronic sequence between the two consecutive exons. In some embodiments of... Petition 870260061675, dated 06 / 23 / 2026, page 29 / 935 22 / 362 of any of the compositions provided in this document, the first or second detectable marker gene is alkaline phosphatase.

[0027] Also provided in this document are compositions that include two different nucleic acid vectors, wherein: a first nucleic acid vector of the two different nucleic acid vectors includes a promoter, a first coding sequence encoding an N-terminal portion of a CLRN1 protein positioned 3' from the promoter, a splice donor sequence positioned at the 3' end of the first coding sequence, and a recombinogenic region of phage F1 positioned 3' from the splice donor sequence; and a second nucleic acid vector of the two different nucleic acid vectors includes a recombinogenic region of phage F1, a splice acceptor sequence positioned 3' from the recombinogenic region of phage F1, a second coding sequence encoding a C-terminal portion of a CLRN1 protein positioned at the 3' end of the splice acceptor sequence, and a polyadenylation signal sequence positioned at the 3' end of the second coding sequence;wherein each of the two coded portions is at least 30 amino acid residues in length; wherein the amino acid sequences of the two coded portions do not overlap with each other; wherein no single vector of the two different vectors encodes a complete CLRN1 protein; and when introduced into a mammalian cell, splicing occurs between the splice donor sequence and the splice acceptor sequence, thus forming a recombined nucleic acid that encodes a complete CLRN1 protein. In some embodiments of any of the compositions provided in this document, the first coding sequence encodes an N-terminal portion of a first isoform of the CLRN1 protein, and the second coding sequence encodes a C-terminal portion of the first isoform of the CLRN1 protein. In some embodiments of; Petition 870260061675, dated 06 / 23 / 2026, page 30 / 935 23 / 362 In any of the compositions provided in this document, the first isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein consists of SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first nucleic acid vector of the second nucleic acid vector further includes a sequence that encodes a second isoform of the CLRN1 protein. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 5.In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes SEQ ID NO: 5. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein consists of SEQ ID NO: 5.

[0028] In some embodiments of any of the compositions provided in this document, the first coding sequence encodes an N-terminal portion of a second isoform of the CLRN1 protein, and the second coding sequence encodes a C-terminal portion of the second isoform of the CLRN1 protein. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 5. In some embodiments of any of the compositions provided in this document, the second isoform of the CLRN1 protein includes SEQ ID NO: 5. In some embodiments of any of the compositions provided in this Petition 870260061675, dated 06 / 23 / 2026, p. 31 / 935 In some embodiments of any of the compositions provided in this document, the first nucleic acid vector or the second nucleic acid vector further includes a sequence encoding a first isoform of the CLRN1 protein. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes a sequence that is at least 95% identical to SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein includes SEQ ID NO: 3. In some embodiments of any of the compositions provided in this document, the first isoform of the CLRN1 protein consists of SEQ ID NO: 3.

[0029] In some embodiments of any of the compositions provided in this document, one or both of the first nucleic acid vector and the second nucleic acid vector comprise a 5' untranslated region (UTR), a 3' UTR, or both. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 10 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 20 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 50 contiguous nucleotides from anywhere within SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 5' UTR includes at least 80 contiguous nucleotides from anywhere within SEQ ID NO: 12.In some versions of any of the compositions provided in this document, the 5' UTR includes a sequence that is by the me. Petition 870260061675, dated 06 / 23 / 2026, p. 32 / 935 25 / 362 in 80% identical to SEQ ID NO: 12. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 10 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 20 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 50 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes at least 80 contiguous nucleotides from anywhere within SEQ ID NO: 15. In some embodiments of any of the compositions provided in this document, the 3' UTR includes a sequence that is at least 80% identical to SEQ ID NO: 15.

[0030] In some embodiments of any of the compositions provided in this document, each of the first nucleic acid vector and second nucleic acid vector is a plasmid, a transposon, a cosmid, an artificial chromosome, or a viral vector. In some embodiments of any of the compositions provided in this document, each of the first nucleic acid vector and second nucleic acid vector is a human artificial chromosome (HAC), a yeast artificial chromosome (YAC), a bacterial artificial chromosome (BAC), or a P1-derived artificial chromosome (PAC). In some embodiments of any of the compositions provided in this document, each of the first nucleic acid vector and second nucleic acid vector is a viral vector selected from an adeno-associated virus (AAV) vector, an adenovirus vector, a lentivirus vector, or a retrovirus vector. In some embodiments of any of the compositions provided Petition 870260061675, dated 06 / 23 / 2026, p. 33 / 935 26 / 362 of the compositions provided in this document, each of the first nucleic acid vector and second nucleic acid vector is an AAV vector. In some embodiments of any of the compositions provided in this document, at least one of the coding sequences includes a nucleotide sequence spanning two consecutive exons of CLRN1 genomic DNA, and without an intronic sequence between the two consecutive exons.

[0031] Kits that include any of the compositions provided in this document are also provided herein. Some embodiments of any of the kits provided in this document also include a pre-filled syringe containing the composition.

[0032] Methods are also provided in this document that involve introducing into the cochlea of ​​a mammal a therapeutically effective amount of any of the compositions provided in this document. In some embodiments of any of the methods provided in this document, the mammal is a human. In some embodiments of any of the compositions provided in this document, the mammal has been previously identified as having a defective CLRN1 gene.

[0033] Methods for increasing the expression of a complete CLRN1 protein in a mammalian cell are also provided in this document, including the introduction of any of the compositions provided in this document into the mammalian cell. In some embodiments of any of the methods provided in this document, the mammalian cell is an inner hair cell of the cochlea or an outer hair cell of the cochlea. In some embodiments of any of the methods provided in this document, the mammalian cell is a retinal cell. In some embodiments of any of the methods provided in this document, the mammalian cell is a human cell. In some embodiments of which Petition 870260061675, dated 06 / 23 / 2026, page 34 / 935 27 / 362 whether one of the methods provided in this document, it has been previously determined that the mammalian cell possesses a defective CLRN1 gene.

[0034] Methods for increasing the expression of a CLRN1 protein in an inner hair cell, an outer hair cell, or both in a mammalian cochlea are also provided in this document, including: introducing a therapeutically effective amount of any of the compositions described in this document into the mammalian cochlea. Methods for increasing the expression of a complete CLRN1 protein in a mammalian eye are also provided in this document, including: intraocular administration of a therapeutically effective amount of any of the compositions provided in this document into the mammalian eye. In some embodiments of any of the compositions provided in this document, the mammal has been previously identified as having a defective CLRN1 gene. In some embodiments of any of the methods provided in this document, the mammal is a human.

[0035] This document also provides methods for treating hearing loss in an individual identified as possessing a defective CLRN1 gene, including: administering a therapeutically effective amount of any of the compositions provided in this document into the individual's cochlea. This document also provides methods for treating vision loss in an individual identified as possessing a defective CLRN1 gene, including: administering a therapeutically effective amount of any of the compositions provided in this document into the individual's eye. In some embodiments of any of the methods provided in this document, the individual has Usher syndrome type III. In some embodiments of any of the Petition 870260061675, dated 06 / 23 / 2026, page 35 / 935 28 / 362 methods provided in this document, the individual is a human being. Some embodiments of any of the methods provided in this document also include, prior to the administration step, determining that the individual possesses a defective CLRN1 gene.

[0036] The terms “a” and “an” refer to one or more of a (i.e., at least one) grammatical object of the article. For example, “an element” encompasses one element and more than one element.

[0037] The term mutation in a CLRN1 gene refers to a modification in a wild-type CLRN1 gene that results in the production of a CLRN1 protein with one or more of the following: a deletion in one or more amino acids, one or more amino acid substitutions, and one or more amino acid insertions compared to the wild-type CLRN1 protein, and / or results in a reduction in the expressed level of the encoded CLRN1 protein in a mammalian cell compared to the expressed level of the encoded CLRN1 protein in a mammalian cell that does not have a mutation. In some embodiments, a mutation may result in the production of a CLRN1 protein with a deletion in one or more amino acids (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids). In some forms, the mutation can result in a shift in the reading frame of the CLRN1 gene.The term frameshift is known in the technique as encompassing any mutation in a coding sequence that results in a change in the reading frame of the coding sequence. In some embodiments, a change in the reading frame can result in a non-functional protein. In some embodiments, a point mutation can be a nonsense mutation (i.e., result in a premature stop codon in an exon of the gene). A nonsense mutation can result in the production of a truncated protein (compared to... Petition 870260061675, dated 06 / 23 / 2026, page 36 / 935 29 / 362 a corresponding wild-type protein) that may or may not be functional. In some embodiments, the mutation may result in the loss (or decrease in the level) of mRNA expression of CLRN1 or CLRN1 protein, or both mRNA and protein. In some embodiments, the mutation may result in the production of an altered CLRN1 protein with a loss or decrease in one or more biological activities (functions) compared to a wild-type CLRN1 protein.

[0038] In some embodiments, the mutation is an insertion of one or more nucleotides into a CLRN1 gene. In some embodiments, the mutation is in a regulatory sequence of the CLRN1 gene, that is, a portion of the gene that is not the coding sequence. In some embodiments, a mutation in a regulatory sequence may be in a promoter or enhancer region and prevent or reduce proper transcription of the CLRN1 gene. The term conservative mutation refers to a mutation that does not alter the amino acid encoded at the mutation site (due to codon degeneracy).

[0039] Modifications can be introduced into a nucleotide sequence by known standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Conservative amino acid substitutions are those in which the amino acid residue is replaced by an amino acid residue that has a similar side chain. Families of amino acid residues with similar side chains have been defined in the technique. Such families include amino acids with basic side chains (e.g., lysine, arginine, and histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, and tryptophan), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, and methionine), chains Petition 870260061675, dated 06 / 23 / 2026, p. 37 / 935 30 / 362 beta-branched side chains (e.g., threonine, valine, and isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, and histidine).

[0040] The term “nucleotide sequence encoding an amino acid sequence” includes all nucleotide sequences that are degenerate versions of each other and therefore encode the same amino acid sequence.

[0041] The term endogenous refers to any material originating from an organism, cell or tissue.

[0042] The term exogenous refers to any material introduced or originating from outside an organism, cell, or tissue that is not produced or does not originate from the same organism, cell, or tissue into which it is being introduced.

[0043] The term isolated means altered or removed from its natural state. For example, a nucleic acid or peptide naturally present in a living animal is not isolated, but the same nucleic acid or peptide partially or completely separated from the coexisting materials of its natural state is isolated. An isolated protein or nucleic acid may exist in a substantially purified form or may exist in a non-native environment, such as, for example, in a host cell.

[0044] The term transfected, transformed, or transduced refers to a process by which exogenous nucleic acid is transferred or introduced into a cell. A transfected, transformed, or transduced mammalian cell is a cell that has been transfected, transformed, or transduced with exogenous nucleic acid.

[0045] The term expression refers to the transcription and / or translation of a particular nucleotide sequence that codes for a protein.

[0046] The term transient expression refers to the expression of an encoding sequence that is not integrated for a short period of time. Petition 870260061675, dated 06 / 23 / 2026, page 38 / 935 31 / 362 time (e.g., hours or days). The coding sequence that is transiently expressed in a cell (e.g., a mammalian cell) is lost after several rounds of cell division.

[0047] The term individual is intended to include any mammal. In some modalities, the individual is a rodent (e.g., a rat or mouse), a rabbit, a sheep, a goat, a pig, a dog, a cat, a non-human primate, or a human. In some modalities, the individual has or is at risk of hearing loss and / or vision loss. In some modalities, the individual was previously identified as having a mutation in a CLRN1 gene. In some modalities, the individual was identified as having a mutation in a CLRN1 gene and was diagnosed with hearing loss and / or vision loss. In some modalities, the individual was identified as having hearing loss and / or vision loss.

[0048] A treatment is therapeutically effective when it results in a reduction in one or more of the number, severity, and frequency of one or more symptoms of a disease (e.g., hearing loss or vision loss) in an individual (e.g., a human). In some modalities, a therapeutically effective amount of a composition may result in an increase in the expression level of an active CLRN1 protein (e.g., a complete wild-type CLRN1 protein or a variant of a CLRN1 protein that has the desired activity) (e.g., compared to the expression level before treatment with the composition). In some modalities, a therapeutically effective amount of a composition may result in an increase in the expression level of an active CLRN1 protein (e.g., a complete wild-type CLRN1 protein or an active variant) in a target cell (e.g., a cochlear inner hair cell). In some Petition 870260061675, dated 06 / 23 / 2026, page 39 / 935 32 / 362 modalities, a therapeutically effective amount of a composition may result in an increase in the expression level of an active CLRN1 protein (e.g., a complete wild-type CLRN1 protein or an active variant) and / or an increase in one or more activities of a CLRN1 protein in a target cell (e.g., compared to a reference level, such as the level(s) in an individual before treatment, the level(s) in an individual with a mutation in a CLRN1 gene, or the level(s) in an individual or a population of individuals with hearing loss and / or vision loss).

[0049] The terms nucleic acid or polynucleotide refer to deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) or combinations thereof, in single-stranded or double-stranded form. Unless specifically limited, the term encompasses nucleic acids containing known analogues of natural nucleotides that possess binding properties similar to the reference nucleotides. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses complementary sequences, as well as the explicitly indicated sequence. In some embodiments of any of the nucleic acids described in this document, the nucleic acid is DNA. In some embodiments of any of the nucleic acids described in this document, the nucleic acid is RNA.

[0050] The term active CLRN1 protein means a DNA-encoded protein that, if replaced by both wild-type alleles encoding full CLRN1 protein in auditory hair cells or eye cells of a mammal that would otherwise be wild-type and is expressed in the auditory hair cells or eye cells of that mammal, causes in that mammal a level of hearing or vision close to the normal level of hearing or vision. Petition 870260061675, dated 06 / 23 / 2026, page 40 / 935 33 / 362 a similar mammal that is entirely wild-type. Non-limiting examples of active CLRN1 proteins are complete CLRN1 proteins (e.g., any of the complete CLRN1 proteins described in this document).

[0051] For example, an active CLRN1 protein may include a sequence of an entire wild-type CLRN1 protein (e.g., a human wild-type entire CLRN1 protein) including 1 amino acid substitution to about 100 amino acid substitutions, 1 amino acid substitution to about 95 amino acid substitutions, 1 amino acid substitution to about 90 amino acid substitutions, 1 amino acid substitution to about 85 amino acid substitutions, 1 amino acid substitution to about 80 amino acid substitutions, 1 amino acid substitution to about 75 amino acid substitutions, 1 amino acid substitution to about 70 amino acid substitutions, 1 amino acid substitution to about 65 amino acid substitutions, 1 amino acid substitution to about 60 amino acid substitutions, 1 amino acid substitution to about 55 amino acid substitutions, 1 amino acid substitution to about 50 amino acid substitutions,1 amino acid substitution leads to approximately 45 amino acid substitutions, 1 amino acid substitution leads to approximately 40 amino acid substitutions, 1 amino acid substitution leads to approximately 35 amino acid substitutions, 1 amino acid substitution leads to approximately 30 amino acid substitutions, 1 amino acid substitution leads to approximately 25 amino acid substitutions, 1 amino acid substitution leads to approximately 20 amino acid substitutions, 1 amino acid substitution leads to approximately 15 amino acid substitutions, 1 amino acid substitution leads to approximately 10 amino acid substitutions, 1 amino acid substitution leads to approximately 9 amino acid substitutions, 1 amino acid substitution leads to approximately 8 amino acid substitutions, 1 amino acid substitution leads to approximately 7 amino acid substitutions. Petition 870260061675, dated 06 / 23 / 2026, p. 41 / 935 34 / 362 amino acid substitutions, 1 amino acid substitution to about 6 amino acid substitutions, 1 amino acid substitution to about 5 amino acid substitutions, 1 amino acid substitution to about 4 amino acid substitutions, 1 amino acid substitution to about 3 amino acid substitutions, from about 2 amino acid substitutions to about 100 amino acid substitutions, from about 2 amino acid substitutions to about 95 amino acid substitutions, from about 2 amino acid substitutions to about 90 amino acid substitutions, from about 2 amino acid substitutions to about 85 amino acid substitutions, from about 2 amino acid substitutions to about 80 amino acid substitutions, from about 2 amino acid substitutions to about 75 amino acid substitutions, from about 2 amino acid substitutions to about 70 amino acid substitutions, from about 2 amino acid substitutions to about of 65 amino acid substitutions,from about 2 amino acid substitutions to about 60 amino acid substitutions, from about 2 amino acid substitutions to about 55 amino acid substitutions, from about 2 amino acid substitutions to about 50 amino acid substitutions, from about 2 amino acid substitutions to about 45 amino acid substitutions, from about 2 amino acid substitutions to about 40 amino acid substitutions, from about 2 amino acid substitutions to about 35 amino acid substitutions, from about 2 amino acid substitutions to about 30 amino acid substitutions, from about 2 amino acid substitutions to about 25 amino acid substitutions, from about 2 amino acid substitutions to about 20 amino acid substitutions, from about 2 amino acid substitutions to about 15 amino acid substitutions, from about 2 amino acid substitutions to about 10 amino acid substitutions,from about 2 amino acid substitutions to about 9 amino acid substitutions, from about 2 substitutions of, Petition 870260061675, dated 06 / 23 / 2026, p. 42 / 935 35 / 362 amino acid to about 8 amino acid substitutions, from about 2 amino acid substitutions to about 7 amino acid substitutions, from about 2 amino acid substitutions to about 6 amino acid substitutions, from about 2 amino acid substitutions to about 5 amino acid substitutions, from about 2 amino acid substitutions to about 4 amino acid substitutions, from about 3 amino acid substitutions to about 100 amino acid substitutions, from about 3 amino acid substitutions to about 95 amino acid substitutions, from about 3 amino acid substitutions to about 90 amino acid substitutions, from about 3 amino acid substitutions to about 85 amino acid substitutions, from about 3 amino acid substitutions to about 80 amino acid substitutions, from about 3 amino acid substitutions to about 75 amino acid substitutions, from about 3 amino acid substitutions to about 70 amino acid substitutions,from about 3 amino acid substitutions to about 65 amino acid substitutions, from about 3 amino acid substitutions to about 60 amino acid substitutions, from about 3 amino acid substitutions to about 55 amino acid substitutions, from about 3 amino acid substitutions to about 50 amino acid substitutions, from about 3 amino acid substitutions to about 45 amino acid substitutions, from about 3 amino acid substitutions to about 40 amino acid substitutions, from about 3 amino acid substitutions to about 35 amino acid substitutions, from about 3 amino acid substitutions to about 30 amino acid substitutions, from about 3 amino acid substitutions to about 25 amino acid substitutions, from about 3 amino acid substitutions to about 20 amino acid substitutions, from about 3 amino acid substitutions to about 15 amino acid substitutions,from about 3 amino acid substitutions to about 10 amino acid substitutions, from about 3 amino acid substitutions, Petition 870260061675, dated 06 / 23 / 2026, p. 43 / 935 36 / 362 of approximately 9 amino acid substitutions, from approximately 3 amino acid substitutions to approximately 8 amino acid substitutions, from approximately 3 amino acid substitutions to approximately 7 amino acid substitutions, from approximately 3 amino acid substitutions to approximately 6 amino acid substitutions, from approximately 3 amino acid substitutions to approximately 5 amino acid substitutions, from approximately 4 amino acid substitutions to approximately 100 amino acid substitutions, from approximately 4 amino acid substitutions to approximately 95 amino acid substitutions, from approximately 4 amino acid substitutions to approximately 90 amino acid substitutions, from approximately 4 amino acid substitutions to approximately 85 amino acid substitutions, from approximately 4 amino acid substitutions to approximately 80 amino acid substitutions, from approximately 4 amino acid substitutions to approximately 75 amino acid substitutions, from approximately 4 amino acid substitutions to approximately of 70 amino acid substitutions,from about 4 amino acid substitutions to about 65 amino acid substitutions, from about 4 amino acid substitutions to about 60 amino acid substitutions, from about 4 amino acid substitutions to about 55 amino acid substitutions, from about 4 amino acid substitutions to about 50 amino acid substitutions, from about 4 amino acid substitutions to about 45 amino acid substitutions, from about 4 amino acid substitutions to about 40 amino acid substitutions, from about 4 amino acid substitutions to about 35 amino acid substitutions, from about 4 amino acid substitutions to about 30 amino acid substitutions, from about 4 amino acid substitutions to about 25 amino acid substitutions, from about 4 amino acid substitutions to about 20 amino acid substitutions, from about 4 amino acid substitutions to about 15 amino acid substitutions,from about 4 amino acid substitutions to about 10 amino acid substitutions, from about 4 amino acid substitutions, Petition 870260061675, dated 06 / 23 / 2026, p. 44 / 935 37 / 362 of approximately 9 amino acid substitutions, from approximately 4 amino acid substitutions to approximately 8 amino acid substitutions, from approximately 4 amino acid substitutions to approximately 7 amino acid substitutions, from approximately 4 amino acid substitutions to approximately 6 amino acid substitutions, from approximately 5 amino acid substitutions to approximately 100 amino acid substitutions, from approximately 5 amino acid substitutions to approximately 95 amino acid substitutions, from approximately 5 amino acid substitutions to approximately 90 amino acid substitutions, from approximately 5 amino acid substitutions to approximately 85 amino acid substitutions, from approximately 5 amino acid substitutions to approximately 80 amino acid substitutions, from approximately 5 amino acid substitutions to approximately 75 amino acid substitutions, from approximately 5 amino acid substitutions to approximately 70 amino acid substitutions, from approximately 5 amino acid substitutions to approximately of 65 amino acid substitutions,from about 5 amino acid substitutions to about 60 amino acid substitutions, from about 5 amino acid substitutions to about 55 amino acid substitutions, from about 5 amino acid substitutions to about 50 amino acid substitutions, from about 5 amino acid substitutions to about 45 amino acid substitutions, from about 5 amino acid substitutions to about 40 amino acid substitutions, from about 5 amino acid substitutions to about 35 amino acid substitutions, from about 5 amino acid substitutions to about 30 amino acid substitutions, from about 5 amino acid substitutions to about 25 amino acid substitutions, from about 5 amino acid substitutions to about 20 amino acid substitutions, from about 5 amino acid substitutions to about 15 amino acid substitutions, from about 5 amino acid substitutions to about 10 amino acid substitutions,from about 5 amino acid substitutions to about 9 amino acid substitutions, from about 5 amino acid substitutions, Petition 870260061675, dated 06 / 23 / 2026, p. 45 / 935 38 / 362 of approximately 8 amino acid substitutions, from approximately 5 amino acid substitutions to approximately 7 amino acid substitutions, from approximately 6 amino acid substitutions to approximately 100 amino acid substitutions, from approximately 6 amino acid substitutions to approximately 95 amino acid substitutions, from approximately 6 amino acid substitutions to approximately 90 amino acid substitutions, from approximately 6 amino acid substitutions to approximately 85 amino acid substitutions, from approximately 6 amino acid substitutions to approximately 80 amino acid substitutions, from approximately 6 amino acid substitutions to approximately 75 amino acid substitutions, from approximately 6 amino acid substitutions to approximately 70 amino acid substitutions, from approximately 6 amino acid substitutions to approximately 65 amino acid substitutions, from approximately 6 amino acid substitutions to approximately 60 amino acid substitutions, from approximately 6 amino acid substitutions approximately 55 amino acid substitutions,from about 6 amino acid substitutions to about 50 amino acid substitutions, from about 6 amino acid substitutions to about 45 amino acid substitutions, from about 6 amino acid substitutions to about 40 amino acid substitutions, from about 6 amino acid substitutions to about 35 amino acid substitutions, from about 6 amino acid substitutions to about 30 amino acid substitutions, from about 6 amino acid substitutions to about 25 amino acid substitutions, from about 6 amino acid substitutions to about 20 amino acid substitutions, from about 6 amino acid substitutions to about 15 amino acid substitutions, from about 6 amino acid substitutions to about 10 amino acid substitutions, from about 6 amino acid substitutions to about 9 amino acid substitutions, from about 6 amino acid substitutions to about 8 amino acid substitutions,from about 7 amino acid substitutions to about 100 amino acid substitutions, from about 7 amino acid substitutions, Petition 870260061675, dated 06 / 23 / 2026, p. 46 / 935 39 / 362 of approximately 95 amino acid substitutions, from approximately 7 amino acid substitutions to approximately 90 amino acid substitutions, from approximately 7 amino acid substitutions to approximately 85 amino acid substitutions, from approximately 7 amino acid substitutions to approximately 80 amino acid substitutions, from approximately 7 amino acid substitutions to approximately 75 amino acid substitutions, from approximately 7 amino acid substitutions to approximately 70 amino acid substitutions, from approximately 7 amino acid substitutions to approximately 65 amino acid substitutions, from approximately 7 amino acid substitutions to approximately 60 amino acid substitutions, from approximately 7 amino acid substitutions to approximately 55 amino acid substitutions, from approximately 7 amino acid substitutions to approximately 50 amino acid substitutions, from approximately 7 amino acid substitutions to approximately 45 amino acid substitutions, from approximately 7 amino acid substitutions to approximately 40 amino acid substitutions of amino acids,from about 7 amino acid substitutions to about 35 amino acid substitutions, from about 7 amino acid substitutions to about 30 amino acid substitutions, from about 7 amino acid substitutions to about 25 amino acid substitutions, from about 7 amino acid substitutions to about 20 amino acid substitutions, from about 7 amino acid substitutions to about 15 amino acid substitutions, from about 7 amino acid substitutions to about 10 amino acid substitutions, from about 7 amino acid substitutions to about 9 amino acid substitutions, from about 8 amino acid substitutions to about 100 amino acid substitutions, from about 8 amino acid substitutions to about 95 amino acid substitutions, from about 8 amino acid substitutions to about 90 amino acid substitutions, from about 8 amino acid substitutions to about 85 amino acid substitutions,from about 8 amino acid substitutions to about 80 amino acid substitutions, from about 8 amino acid substitutions, Petition 870260061675, dated 06 / 23 / 2026, p. 47 / 935 40 / 362 of approximately 75 amino acid substitutions, from approximately 8 amino acid substitutions to approximately 70 amino acid substitutions, from approximately 8 amino acid substitutions to approximately 65 amino acid substitutions, from approximately 8 amino acid substitutions to approximately 60 amino acid substitutions, from approximately 8 amino acid substitutions to approximately 55 amino acid substitutions, from approximately 8 amino acid substitutions to approximately 50 amino acid substitutions, from approximately 8 amino acid substitutions to approximately 45 amino acid substitutions, from approximately 8 amino acid substitutions to approximately 40 amino acid substitutions, from approximately 8 amino acid substitutions to approximately 35 amino acid substitutions, from approximately 8 amino acid substitutions to approximately 30 amino acid substitutions, from approximately 8 amino acid substitutions to approximately 25 amino acid substitutions, from approximately 8 amino acid substitutions to approximately 20 amino acid substitutions,from about 8 amino acid substitutions to about 15 amino acid substitutions, from about 8 amino acid substitutions to about 10 amino acid substitutions, from about 10 amino acid substitutions to about 100 amino acid substitutions, from about 10 amino acid substitutions to about 95 amino acid substitutions, from about 10 amino acid substitutions to about 90 amino acid substitutions, from about 10 amino acid substitutions to about 85 amino acid substitutions, from about 10 amino acid substitutions to about 80 amino acid substitutions, from about 10 amino acid substitutions to about 75 amino acid substitutions, from about 10 amino acid substitutions to about 70 amino acid substitutions, from about 10 amino acid substitutions to about 65 amino acid substitutions, from about 10 amino acid substitutions to about 60 amino acid substitutions,from about 10 amino acid substitutions to about 55 amino acid substitutions, from about 10 substitutions, Petition 870260061675, dated 06 / 23 / 2026, p. 48 / 935 41 / 362 of amino acid to about 50 amino acid substitutions, from about 10 amino acid substitutions to about 45 amino acid substitutions, from about 10 amino acid substitutions to about 40 amino acid substitutions, from about 10 amino acid substitutions to about 35 amino acid substitutions, from about 10 amino acid substitutions to about 30 amino acid substitutions, from about 10 amino acid substitutions to about 25 amino acid substitutions, from about 10 amino acid substitutions to about 20 amino acid substitutions, from about 10 amino acid substitutions to about 15 amino acid substitutions, from about 15 amino acid substitutions to about 100 amino acid substitutions, from about 15 amino acid substitutions to about 95 amino acid substitutions, from about 15 amino acid substitutions to about 90 amino acid substitutions,from about 15 amino acid substitutions to about 85 amino acid substitutions, from about 15 amino acid substitutions to about 80 amino acid substitutions, from about 15 amino acid substitutions to about 75 amino acid substitutions, from about 15 amino acid substitutions to about 70 amino acid substitutions, from about 15 amino acid substitutions to about 65 amino acid substitutions, from about 15 amino acid substitutions to about 60 amino acid substitutions, from about 15 amino acid substitutions to about 55 amino acid substitutions, from about 15 amino acid substitutions to about 50 amino acid substitutions, from about 15 amino acid substitutions to about 45 amino acid substitutions, from about 15 amino acid substitutions to about 40 amino acid substitutions, from about 15 amino acid substitutions to about 35 amino acid substitutions,from about 15 amino acid substitutions to about 30 amino acid substitutions, from about 15 amino acid substitutions to about 25 amino acid substitutions, from about, Petition 870260061675, dated 06 / 23 / 2026, p. 49 / 935 42 / 362 amino acid substitutions to about 20 amino acid substitutions, from about 20 amino acid substitutions to about 100 amino acid substitutions, from about 20 amino acid substitutions to about 95 amino acid substitutions, from about 20 amino acid substitutions to about 90 amino acid substitutions, from about 20 amino acid substitutions to about 85 amino acid substitutions, from about 20 amino acid substitutions to about 80 amino acid substitutions, from about 20 amino acid substitutions to about 75 amino acid substitutions, from about 20 amino acid substitutions to about 70 amino acid substitutions, from about 20 amino acid substitutions to about 65 amino acid substitutions, from about 20 amino acid substitutions to about 60 amino acid substitutions, from about 20 amino acid substitutions to about 55 amino acid substitutions,from about 20 amino acid substitutions to about 50 amino acid substitutions, from about 20 amino acid substitutions to about 45 amino acid substitutions, from about 20 amino acid substitutions to about 40 amino acid substitutions, from about 20 amino acid substitutions to about 35 amino acid substitutions, from about 20 amino acid substitutions to about 30 amino acid substitutions, from about 20 amino acid substitutions to about 25 amino acid substitutions, from about 25 amino acid substitutions to about 100 amino acid substitutions, from about 25 amino acid substitutions to about 95 amino acid substitutions, from about 25 amino acid substitutions to about 90 amino acid substitutions, from about 25 amino acid substitutions to about 85 amino acid substitutions, from about 25 amino acid substitutions to about 80 amino acid substitutions,from about 25 amino acid substitutions to about 75 amino acid substitutions, from about 25 amino acid substitutions to about 70 substitutions, Petition 870260061675, dated 06 / 23 / 2026, p. 50 / 935 43 / 362 amino acid substitutions, from about 25 amino acid substitutions to about 65 amino acid substitutions, from about 25 amino acid substitutions to about 60 amino acid substitutions, from about 25 amino acid substitutions to about 55 amino acid substitutions, from about 25 amino acid substitutions to about 50 amino acid substitutions, from about 25 amino acid substitutions to about 45 amino acid substitutions, from about 25 amino acid substitutions to about 40 amino acid substitutions, from about 25 amino acid substitutions to about 35 amino acid substitutions, from about 25 amino acid substitutions to about 30 amino acid substitutions, from about 30 amino acid substitutions to about 100 amino acid substitutions, from about 30 amino acid substitutions to about 95 amino acid substitutions, from about 30 amino acid substitutions to approximately 90 amino acid substitutions,from about 30 amino acid substitutions to about 85 amino acid substitutions, from about 30 amino acid substitutions to about 80 amino acid substitutions, from about 30 amino acid substitutions to about 75 amino acid substitutions, from about 30 amino acid substitutions to about 70 amino acid substitutions, from about 30 amino acid substitutions to about 65 amino acid substitutions, from about 30 amino acid substitutions to about 60 amino acid substitutions, from about 30 amino acid substitutions to about 55 amino acid substitutions, from about 30 amino acid substitutions to about 50 amino acid substitutions, from about 30 amino acid substitutions to about 45 amino acid substitutions, from about 30 amino acid substitutions to about 40 amino acid substitutions, from about 30 amino acid substitutions to about 35 amino acid substitutions,from about 35 amino acid substitutions to about 100 amino acid substitutions, from about 35 amino acid substitutions, Petition 870260061675, dated 06 / 23 / 2026, p. 51 / 935 44 / 362 acid to about 95 amino acid substitutions, from about 35 amino acid substitutions to about 90 amino acid substitutions, from about 35 amino acid substitutions to about 85 amino acid substitutions, from about 35 amino acid substitutions to about 80 amino acid substitutions, from about 35 amino acid substitutions to about 75 amino acid substitutions, from about 35 amino acid substitutions to about 70 amino acid substitutions, from about 35 amino acid substitutions to about 65 amino acid substitutions, from about 35 amino acid substitutions to about 60 amino acid substitutions, from about 35 amino acid substitutions to about 55 amino acid substitutions, from about 35 amino acid substitutions to about 50 amino acid substitutions, from about 35 amino acid substitutions to about 45 amino acid substitutions amino acids, from about 35 amino acid substitutions to about 40 amino acid substitutions,from about 40 amino acid substitutions to about 100 amino acid substitutions, from about 40 amino acid substitutions to about 95 amino acid substitutions, from about 40 amino acid substitutions to about 90 amino acid substitutions, from about 40 amino acid substitutions to about 85 amino acid substitutions, from about 40 amino acid substitutions to about 80 amino acid substitutions, from about 40 amino acid substitutions to about 75 amino acid substitutions, from about 40 amino acid substitutions to about 70 amino acid substitutions, from about 40 amino acid substitutions to about 65 amino acid substitutions, from about 40 amino acid substitutions to about 60 amino acid substitutions, from about 40 amino acid substitutions to about 55 amino acid substitutions, from about 40 amino acid substitutions to about 50 amino acid substitutions,from about 40 amino acid substitutions to about 45 amino acid substitutions, from about, Petition 870260061675, dated 06 / 23 / 2026, p. 52 / 935 45 / 362 amino acid substitutions to about 100 amino acid substitutions, from about 45 amino acid substitutions to about 95 amino acid substitutions, from about 45 amino acid substitutions to about 90 amino acid substitutions, from about 45 amino acid substitutions to about 85 amino acid substitutions, from about 45 amino acid substitutions to about 80 amino acid substitutions, from about 45 amino acid substitutions to about 75 amino acid substitutions, from about 45 amino acid substitutions to about 70 amino acid substitutions, from about 45 amino acid substitutions to about 65 amino acid substitutions, from about 45 amino acid substitutions to about 60 amino acid substitutions, from about 45 amino acid substitutions to about 55 amino acid substitutions, from about 45 amino acid substitutions to about 50 amino acid substitutions,from about 50 amino acid substitutions to about 100 amino acid substitutions, from about 50 amino acid substitutions to about 95 amino acid substitutions, from about 50 amino acid substitutions to about 90 amino acid substitutions, from about 50 amino acid substitutions to about 85 amino acid substitutions, from about 50 amino acid substitutions to about 80 amino acid substitutions, from about 50 amino acid substitutions to about 75 amino acid substitutions, from about 50 amino acid substitutions to about 70 amino acid substitutions, from about 50 amino acid substitutions to about 65 amino acid substitutions, from about 50 amino acid substitutions to about 60 amino acid substitutions, from about 50 amino acid substitutions to about 55 amino acid substitutions, from about 60 amino acid substitutions to about out of 100 amino acid substitutions,from about 60 amino acid substitutions to about 95 amino acid substitutions, from about 60 amino acid substitutions to about 90, Petition 870260061675, dated 06 / 23 / 2026, p. 53 / 935 46 / 362 amino acid substitutions, from about 60 amino acid substitutions to about 85 amino acid substitutions, from about 60 amino acid substitutions to about 80 amino acid substitutions, from about 60 amino acid substitutions to about 75 amino acid substitutions, from about 60 amino acid substitutions to about 70 amino acid substitutions, from about 60 amino acid substitutions to about 65 amino acid substitutions, from about 70 amino acid substitutions to about 100 amino acid substitutions, from about 70 amino acid substitutions to about 95 amino acid substitutions, from about 70 amino acid substitutions to about 90 amino acid substitutions, from about 70 amino acid substitutions to about 85 amino acid substitutions, from about 70 amino acid substitutions to about 80 amino acid substitutions, from about 70 amino acid substitutions to about 75 amino acid substitutions,from about 80 amino acid substitutions to about 100 amino acid substitutions, from about 80 amino acid substitutions to about 95 amino acid substitutions, from about 80 amino acid substitutions to about 90 amino acid substitutions, from about 80 amino acid substitutions to about 85 amino acid substitutions, from about 90 amino acid substitutions to about 100 amino acid substitutions, from about 90 amino acid substitutions to about 95 amino acid substitutions, or from about 95 amino acids to about 100 amino acids.

[0052] A person skilled in the art would appreciate that amino acids that are not conserved between wild-type CLRN1 proteins of different species can be mutated without losing activity, whereas amino acids that are conserved between wild-type CLRN1 proteins of different species should not be mutated, as it is more likely (than amino acids that are not conserved between different species) that they are involved in the activity. Petition 870260061675, dated 06 / 23 / 2026, page 54 / 935 47 / 362

[0053] An active CLRN1 protein may include, for example, a sequence of a whole wild-type CLRN1 protein (e.g., a whole human wild-type CLRN1 protein) that has from about 1 amino acid to about 100 amino acids, from about 1 amino acid to about 95 amino acids, from about 1 amino acid to about 90 amino acids, from about 1 amino acid to about 85 amino acids, from about 1 amino acid to about 80 amino acids, from about 1 amino acid to about 75 amino acids, from about 1 amino acid to about 70 amino acids, from about 1 amino acid to about 65 amino acids, from about 1 amino acid to about 60 amino acids, from about 1 amino acid to about 55 amino acids, from about 1 amino acid to about 50 amino acids, from about 1 amino acid to about 45 amino acids, from about 1 amino acid to about 40 amino acids, from about 1 amino acid to about 35 amino acids, from about 1 amino acid to about 30 amino acids,from about 1 amino acid to about 25 amino acids, from about 1 amino acid to about 20 amino acids, from about 1 amino acid to about 15 amino acids, from about 1 amino acid to about 10 amino acids, from about 1 amino acid to about 9 amino acids, from about 1 amino acid to about 8 amino acids, from about 1 amino acid to about 7 amino acids, from about 1 amino acid to about 6 amino acids, from about 1 amino acid to about 5 amino acids, from about 1 amino acid to about 4 amino acids, from about 1 amino acid to about 3 amino acids, from about 2 amino acids to about 100 amino acids, from about 2 amino acids to about 95 amino acids, from about 2 amino acids to about 90 amino acids, from about 2 amino acids to about 85 amino acids, from about 2 amino acids to about 80 amino acids, from about 2 amino acids to about 75 amino acids, from about 2 amino acids to about 70 amino acids, from about 2 amino acids to about 65 amino acids,of approximately 2 amino acids, Petition 870260061675, dated 06 / 23 / 2026, page 55 / 935 48 / 362 two to about 60 amino acids, from about 2 amino acids to about 55 amino acids, from about 2 amino acids to about 50 amino acids, from about 2 amino acids to about 45 amino acids, from about 2 amino acids to about 40 amino acids, from about 2 amino acids to about 35 amino acids, from about 2 amino acids to about 30 amino acids, from about 2 amino acids to about 25 amino acids, from about 2 amino acids to about 20 amino acids, from about 2 amino acids to about 15 amino acids, from about 2 amino acids to about 10 amino acids, from about 2 amino acids to about 9 amino acids, from about 2 amino acids to about 8 amino acids, from about 2 amino acids to about 7 amino acids, from about 2 amino acids to about 6 amino acids, from about 2 amino acids to about 5 amino acids, from about 2 amino acids to about 4 amino acids, from about 3 amino acids to about 100 amino acids, from about 3 amino acids to about 95 amino acids,from about 3 amino acids to about 90 amino acids, from about 3 amino acids to about 85 amino acids, from about 3 amino acids to about 80 amino acids, from about 3 amino acids to about 75 amino acids, from about 3 amino acids to about 70 amino acids, from about 3 amino acids to about 65 amino acids, from about 3 amino acids to about 60 amino acids, from about 3 amino acids to about 55 amino acids, from about 3 amino acids to about 50 amino acids, from about 3 amino acids to about 45 amino acids, from about 3 amino acids to about 40 amino acids, from about 3 amino acids to about 35 amino acids, from about 3 amino acids to about 30 amino acids, from about 3 amino acids to about 25 amino acids, from about 3 amino acids to about 20 amino acids, from about 3 amino acids to about 15 amino acids, from about 3 amino acids to about 10 amino acids, from about 3 amino acids to about of 9 amino acids,from about 3 amino acids to about 8 amino acids, from, Petition 870260061675, dated 06 / 23 / 2026, p. 56 / 935 49 / 362 from about 3 amino acids to about 7 amino acids, from about 3 amino acids to about 6 amino acids, from about 3 amino acids to about 5 amino acids, from about 4 amino acids to about 100 amino acids, from about 4 amino acids to about 95 amino acids, from about 4 amino acids to about 90 amino acids, from about 4 amino acids to about 85 amino acids, from about 4 amino acids to about 80 amino acids, from about 4 amino acids to about 75 amino acids, from about 4 amino acids to about 70 amino acids, from about 4 amino acids to about 65 amino acids, from about 4 amino acids to about 60 amino acids, from about 4 amino acids to about 55 amino acids, from about 4 amino acids to about 50 amino acids, from about 4 amino acids to about 45 amino acids, from about 4 amino acids to about 40 amino acids, from about 4 amino acids to about 35 amino acids, from about 4 amino acids to about 30 amino acids,from about 4 amino acids to about 25 amino acids, from about 4 amino acids to about 20 amino acids, from about 4 amino acids to about 15 amino acids, from about 4 amino acids to about 10 amino acids, from about 4 amino acids to about 9 amino acids, from about 4 amino acids to about 8 amino acids, from about 4 amino acids to about 7 amino acids, from about 4 amino acids to about 6 amino acids, from about 5 amino acids to about 100 amino acids, from about 5 amino acids to about 95 amino acids, from about 5 amino acids to about 90 amino acids, from about 5 amino acids to about 85 amino acids, from about 5 amino acids to about 80 amino acids, from about 5 amino acids to about 75 amino acids, from about 5 amino acids to about 70 amino acids, from about 5 amino acids to about 65 amino acids, from about 5 amino acids to about 60 amino acids, from about 5 amino acids to about 55 amino acids,from about 5 amino acids to about 50 amino acids, from about 5 amino acids to, Petition 870260061675, dated 06 / 23 / 2026, p. 57 / 935 50 / 362 approximately 45 amino acids, from approximately 5 amino acids to approximately 40 amino acids, from approximately 5 amino acids to approximately 35 amino acids, from approximately 5 amino acids to approximately 30 amino acids, from approximately 5 amino acids to approximately 25 amino acids, from approximately 5 amino acids to approximately 20 amino acids, from approximately 5 amino acids to approximately 15 amino acids, from approximately 5 amino acids to approximately 10 amino acids, from approximately 5 amino acids to approximately 9 amino acids, from approximately 5 amino acids to approximately 8 amino acids, from approximately 5 amino acids to approximately 7 amino acids, from approximately 6 amino acids to approximately 100 amino acids, from approximately 6 amino acids to approximately 95 amino acids, from approximately 6 amino acids to approximately 90 amino acids, from approximately 6 amino acids to approximately 85 amino acids, from approximately 6 amino acids to approximately 80 amino acids, from approximately 6 amino acids to approximately 75 amino acids, from approximately 6 amino acids to approximately 70 amino acids, from about 6 amino acids to about 65 amino acids,from about 6 amino acids to about 60 amino acids, from about 6 amino acids to about 55 amino acids, from about 6 amino acids to about 50 amino acids, from about 6 amino acids to about 45 amino acids, from about 6 amino acids to about 40 amino acids, from about 6 amino acids to about 35 amino acids, from about 6 amino acids to about 30 amino acids, from about 6 amino acids to about 25 amino acids, from about 6 amino acids to about 20 amino acids, from about 6 amino acids to about 15 amino acids, from about 6 amino acids to about 10 amino acids, from about 6 amino acids to about 9 amino acids, from about 6 amino acids to about 8 amino acids, from about 7 amino acids to about 100 amino acids, from about 7 amino acids to about 95 amino acids, from about 7 amino acids to about 90 amino acids, from about 7 amino acids to about 85 amino acids, from about 7 amino acids to about 80 amino acids,from about 7 amino acids to about 75 amino acids, Petition 870260061675, dated 06 / 23 / 2026, p. 58 / 935 51 / 362 from approximately 7 amino acids to approximately 70 amino acids, from approximately 7 amino acids to approximately 65 amino acids, from approximately 7 amino acids to approximately 60 amino acids, from approximately 7 amino acids to approximately 55 amino acids, from approximately 7 amino acids to approximately 50 amino acids, from approximately 7 amino acids to approximately 45 amino acids, from approximately 7 amino acids to approximately 40 amino acids, from approximately 7 amino acids to approximately 35 amino acids, from approximately 7 amino acids to approximately 30 amino acids, from approximately 7 amino acids to approximately 25 amino acids, from approximately 7 amino acids to approximately 20 amino acids, from approximately 7 amino acids to approximately 15 amino acids, from approximately 7 amino acids to approximately 10 amino acids, from approximately 7 amino acids to approximately 9 amino acids, from approximately 8 amino acids to approximately 100 amino acids, from approximately 8 amino acids to approximately 95 amino acids, from approximately 8 amino acids to approximately 90 amino acids, of from approximately 8 amino acids to approximately 85 amino acids,from about 8 amino acids to about 80 amino acids, from about 8 amino acids to about 75 amino acids, from about 8 amino acids to about 70 amino acids, from about 8 amino acids to about 65 amino acids, from about 8 amino acids to about 60 amino acids, from about 8 amino acids to about 55 amino acids, from about 8 amino acids to about 50 amino acids, from about 8 amino acids to about 45 amino acids, from about 8 amino acids to about 40 amino acids, from about 8 amino acids to about 35 amino acids, from about 8 amino acids to about 30 amino acids, from about 8 amino acids to about 25 amino acids, from about 8 amino acids to about 20 amino acids, from about 8 amino acids to about 15 amino acids, from about 8 amino acids to about 10 amino acids, from about 10 amino acids to about 100 amino acids, from about 10 amino acids to about 95 amino acids, from about 10 amino acids to approximately 90 amino acids,from about 10 amino acids to about 85 amino acids, from about 10 amino acids, Petition 870260061675, dated 06 / 23 / 2026, p. 59 / 935 52 / 362 two to about 80 amino acids, from about 10 amino acids to about 75 amino acids, from about 10 amino acids to about 70 amino acids, from about 10 amino acids to about 65 amino acids, from about 10 amino acids to about 60 amino acids, from about 10 amino acids to about 55 amino acids, from about 10 amino acids to about 50 amino acids, from about 10 amino acids to about 45 amino acids, from about 10 amino acids to about 40 amino acids, from about 10 amino acids to about 35 amino acids, from about 10 amino acids to about 30 amino acids, from about 10 amino acids to about 25 amino acids, from about 10 amino acids to about 20 amino acids, from about 10 amino acids to about 15 amino acids, from about 15 amino acids to about 100 amino acids, from about 15 amino acids to about 95 amino acids, from about 15 amino acids to about 90 amino acids, from about 15 amino acids to about 85 amino acids,from about 15 amino acids to about 80 amino acids, from about 15 amino acids to about 75 amino acids, from about 15 amino acids to about 70 amino acids, from about 15 amino acids to about 65 amino acids, from about 15 amino acids to about 60 amino acids, from about 15 amino acids to about 55 amino acids, from about 15 amino acids to about 50 amino acids, from about 15 amino acids to about 45 amino acids, from about 15 amino acids to about 40 amino acids, from about 15 amino acids to about 35 amino acids, from about 15 amino acids to about 30 amino acids, from about 15 amino acids to about 25 amino acids, from about 15 amino acids to about 20 amino acids, from about 20 amino acids to about 100 amino acids, from about 20 amino acids to about 95 amino acids, from about 20 amino acids to about 90 amino acids, from about 20 amino acids to about 85 amino acids, from about 20 amino acids to about 80 amino acids,from about 20 amino acids to about 75 amino acids, from, Petition 870260061675, dated 06 / 23 / 2026, p. 60 / 935 53 / 362 from approximately 20 amino acids to approximately 70 amino acids, from approximately 20 amino acids to approximately 65 amino acids, from approximately 20 amino acids to approximately 60 amino acids, from approximately 20 amino acids to approximately 55 amino acids, from approximately 20 amino acids to approximately 50 amino acids, from approximately 20 amino acids to approximately 45 amino acids, from approximately 20 amino acids to approximately 40 amino acids, from approximately 20 amino acids to approximately 35 amino acids, from approximately 20 amino acids to approximately 30 amino acids, from approximately 20 amino acids to approximately 25 amino acids, from approximately 25 amino acids to approximately 100 amino acids, from approximately 25 amino acids to approximately 95 amino acids, from approximately 25 amino acids to approximately 90 amino acids, from approximately 25 amino acids to approximately 85 amino acids, from approximately 25 amino acids to approximately 80 amino acids, from approximately 25 amino acids to approximately 75 amino acids, from about 25 amino acids to about 70 amino acids, from about 25 amino acids to about 65 amino acids,from approximately 25 amino acids to approximately 60 amino acids, from approximately 25 amino acids to approximately 55 amino acids, from approximately 25 amino acids to approximately 50 amino acids, from approximately 25 amino acids to approximately 45 amino acids, from approximately 25 amino acids to approximately 40 amino acids, from approximately 25 amino acids to approximately 35 amino acids, from approximately 25 amino acids to approximately 30 amino acids, from approximately 30 amino acids to approximately 100 amino acids, from approximately 30 amino acids to approximately 95 amino acids, from approximately 30 amino acids to approximately 90 amino acids, from approximately 30 amino acids to approximately 85 amino acids, from approximately 30 amino acids to approximately 80 amino acids, from approximately 30 amino acids to approximately 75 amino acids, from approximately 30 amino acids to approximately 70 amino acids, from approximately 30 amino acids to approximately 65 amino acids, from approximately 30 amino acids to approximately 60 amino acids, from approximately 30 amino acids to about 55 amino acids, from about 30 amino acids to about 50 amino acids,from about 30 amino acids to about, Petition 870260061675, dated 06 / 23 / 2026, p. 61 / 935 54 / 362 of 45 amino acids, from approximately 30 amino acids to approximately 40 amino acids, from approximately 30 amino acids to approximately 35 amino acids, from approximately 35 amino acids to approximately 50 amino acids, from approximately 35 amino acids to approximately 45 amino acids, from approximately 35 amino acids to approximately 40 amino acids, from approximately 40 amino acids to approximately 100 amino acids, from approximately 40 amino acids to approximately 95 amino acids, from approximately 40 amino acids to approximately 90 amino acids, from approximately 40 amino acids to approximately 85 amino acids, from approximately 40 amino acids to approximately 80 amino acids, from approximately 40 amino acids to approximately 75 amino acids, from approximately 40 amino acids to approximately 70 amino acids, from approximately 40 amino acids to approximately 65 amino acids, from approximately 40 amino acids to approximately 60 amino acids, from approximately 40 amino acids to approximately 55 amino acids, from approximately 40 amino acids to about 50 amino acids, from about 40 amino acids to about 45 amino acids, from about 45 amino acids to about 50 amino acids,From about 50 to about 100 amino acids, from about 50 to about 95 amino acids, from about 50 to about 90 amino acids, from about 50 to about 85 amino acids, from about 50 to about 80 amino acids, from about 50 to about 75 amino acids, from about 50 to about 70 amino acids, from about 50 to about 65 amino acids, from about 50 to about 60 amino acids, or from about 50 to about 55 amino acids, deleted. In some embodiments where two or more amino acids are deleted from the sequence of a complete wild-type CLRN1 protein, at least two of the two or more deleted amino acids may be contiguous in the sequence of the complete wild-type protein. In other instances where two or more amino acids are deleted from the sequence of a complete wild-type CLRN1 protein, some or all of the two or more amino acids may be contiguous in the sequence of the complete wild-type protein. Petition 870260061675, dated 06 / 23 / 2026, page 62 / 935 55 / 362 of the deleted amino acids are not contiguous in the complete wild-type protein sequence. A person skilled in the art would appreciate that amino acids that are not conserved between complete wild-type CLRN1 proteins of different species can be deleted without loss of activity, while amino acids that are conserved between complete wild-type CLRN1 proteins of different species should not be deleted because they are more likely (than amino acids that are not conserved between different species) to be involved in activity.

[0054] In some examples, an active CLRN1 protein may, for instance, include a sequence of a complete wild-type CLRN1 protein that has 1 amino acid to about 100 amino acids, 1 amino acid to about 95 amino acids, 1 amino acid to about 90 amino acids, 1 amino acid to about 85 amino acids, 1 amino acid to about 80 amino acids, 1 amino acid to about 75 amino acids, 1 amino acid to about 70 amino acids, 1 amino acid to about 65 amino acids, 1 amino acid to about 60 amino acids, 1 amino acid to about 55 amino acids, 1 amino acid to about 50 amino acids, 1 amino acid to about 45 amino acids, 1 amino acid to about 40 amino acids, 1 amino acid to about 35 amino acids, 1 amino acid to about 30 amino acids, 1 amino acid to about 25 amino acids, 1 amino acid to about 20 amino acids, 1 amino acid to about 15 amino acids, 1 amino acid to about 10 amino acids, 1 amino acid to about 9 amino acids, 1 amino acid to about 8 amino acids,1 amino acid to about 7 amino acids, 1 amino acid to about 6 amino acids, 1 amino acid to about 5 amino acids, 1 amino acid to about 4 amino acids, 1 amino acid to about 3 amino acids, about 2 amino acids to about 100 amino acids, about 2 amino acids to about 95 amino acids, about 2 amino acids to about 90 amino acids, about 2 amino acids to about 85 amino acids, cer, Petition 870260061675, dated 06 / 23 / 2026, page 63 / 935 56 / 362 ca from 2 amino acids to about 80 amino acids, about 2 amino acids to about 75 amino acids, about 2 amino acids to about 70 amino acids, about 2 amino acids to about 65 amino acids, about 2 amino acids to about 60 amino acids, about 2 amino acids to about 55 amino acids, about 2 amino acids to about 50 amino acids, about 2 amino acids to about 45 amino acids, about 2 amino acids to about 40 amino acids, about 2 amino acids to about 35 amino acids, about 2 amino acids to about 30 amino acids, about 2 amino acids to about 25 amino acids, about 2 amino acids to about 20 amino acids, about 2 amino acids to about 15 amino acids, about 2 amino acids to about 10 amino acids, about 2 amino acids to about 9 amino acids, about 2 amino acids to about 8 amino acids, about 2 amino acids to about 7 amino acids, about 2 amino acids to about 6 amino acids, from about 2 amino acids to about 5 amino acids,from approximately 2 amino acids to approximately 4 amino acids, from approximately 3 amino acids to approximately 100 amino acids, from approximately 3 amino acids to approximately 95 amino acids, from approximately 3 amino acids to approximately 90 amino acids, from approximately 3 amino acids to approximately 85 amino acids, from approximately 3 amino acids to approximately 80 amino acids, from approximately 3 amino acids to approximately 75 amino acids, from approximately 3 amino acids to approximately 70 amino acids, from approximately 3 amino acids to approximately 65 amino acids, from approximately 3 amino acids to approximately 60 amino acids, from approximately 3 amino acids to approximately 55 amino acids, from approximately 3 amino acids to approximately 50 amino acids, from approximately 3 amino acids to approximately 45 amino acids, from approximately 3 amino acids to approximately 40 amino acids, from approximately 3 amino acids to approximately 35 amino acids, from approximately 3 amino acids to approximately 30 amino acids, from approximately 3 amino acids to approximately 25 amino acids, from approximately 3 amino acids to approximately 20 amino acids, from approximately 3 amino acids to approximately 15 amino acids, from about 3 amino acids to about 10 amino acids,cer, Petition 870260061675, dated 06 / 23 / 2026, p. 64 / 935 57 / 362 ca from 3 amino acids to about 9 amino acids, about 3 amino acids to about 8 amino acids, about 3 amino acids to about 7 amino acids, about 3 amino acids to about 6 amino acids, about 3 amino acids to about 5 amino acids, about 4 amino acids to about 100 amino acids, about 4 amino acids to about 95 amino acids, about 4 amino acids to about 90 amino acids, about 4 amino acids to about 85 amino acids, about 4 amino acids to about 80 amino acids, about 4 amino acids to about 75 amino acids, about 4 amino acids to about 70 amino acids, about 4 amino acids to about 65 amino acids, about 4 amino acids to about 60 amino acids, about 4 amino acids to about 55 amino acids, about 4 amino acids to about 50 amino acids, about 4 amino acids to about 45 amino acids, about 4 amino acids to about 40 amino acids, about 4 amino acids to about 35 amino acids, from approximately 4 amino acids to approximately 30 amino acids,from approximately 4 amino acids to approximately 25 amino acids, from approximately 4 amino acids to approximately 20 amino acids, from approximately 4 amino acids to approximately 15 amino acids, from approximately 4 amino acids to approximately 10 amino acids, from approximately 4 amino acids to approximately 9 amino acids, from approximately 4 amino acids to approximately 8 amino acids, from approximately 4 amino acids to approximately 7 amino acids, from approximately 4 amino acids to approximately 6 amino acids, from approximately 5 amino acids to approximately 100 amino acids, from approximately 5 amino acids to approximately 95 amino acids, from approximately 5 amino acids to approximately 90 amino acids, from approximately 5 amino acids to approximately 85 amino acids, from approximately 5 amino acids to approximately 80 amino acids, from approximately 5 amino acids to approximately 75 amino acids, from approximately 5 amino acids to approximately 70 amino acids, from approximately 5 amino acids to approximately 65 amino acids, from approximately 5 amino acids to approximately 60 amino acids, from approximately 5 amino acids to approximately 55 amino acids, from approximately 5 amino acids to approximately 50 amino acids, from approximately from 5 amino acids to about 45 amino acids, cer, Petition 870260061675, dated 06 / 23 / 2026, p. 65 / 935 58 / 362 ca from 5 amino acids to about 40 amino acids, about 5 amino acids to about 35 amino acids, about 5 amino acids to about 30 amino acids, about 5 amino acids to about 25 amino acids, about 5 amino acids to about 20 amino acids, about 5 amino acids to about 15 amino acids, about 5 amino acids to about 10 amino acids, about 5 amino acids to about 9 amino acids, about 5 amino acids to about 8 amino acids, about 5 amino acids to about 7 amino acids, about 6 amino acids to about 100 amino acids, about 6 amino acids to about 95 amino acids, about 6 amino acids to about 90 amino acids, about 6 amino acids to about 85 amino acids, about 6 amino acids to about 80 amino acids, about 6 amino acids to about 75 amino acids, about 6 amino acids to about 70 amino acids, about 6 amino acids to about 65 amino acids, about 6 amino acids to approximately 60 amino acids, approximately 6 amino acids to approximately 55 amino acids,from approximately 6 amino acids to approximately 50 amino acids, from approximately 6 amino acids to approximately 45 amino acids, from approximately 6 amino acids to approximately 40 amino acids, from approximately 6 amino acids to approximately 35 amino acids, from approximately 6 amino acids to approximately 30 amino acids, from approximately 6 amino acids to approximately 25 amino acids, from approximately 6 amino acids to approximately 20 amino acids, from approximately 6 amino acids to approximately 15 amino acids, from approximately 6 amino acids to approximately 10 amino acids, from approximately 6 amino acids to approximately 9 amino acids, from approximately 6 amino acids to approximately 8 amino acids, from approximately 7 amino acids to approximately 100 amino acids, from approximately 7 amino acids to approximately 95 amino acids, from approximately 7 amino acids to approximately 90 amino acids, from approximately 7 amino acids to approximately 85 amino acids, from approximately 7 amino acids to approximately 80 amino acids, from approximately 7 amino acids to approximately 75 amino acids, from approximately 7 amino acids to approximately 70 amino acids, from approximately 7 amino acids to approximately 65 amino acids, from about 7 amino acids to about 60 amino acids, Petition 870260061675, dated 06 / 23 / 2026, p. 66 / 935 59 / 362 from approximately 7 amino acids to approximately 55 amino acids, from approximately 7 amino acids to approximately 50 amino acids, from approximately 7 amino acids to approximately 45 amino acids, from approximately 7 amino acids to approximately 40 amino acids, from approximately 7 amino acids to approximately 35 amino acids, from approximately 7 amino acids to approximately 30 amino acids, from approximately 7 amino acids to approximately 25 amino acids, from approximately 7 amino acids to approximately 20 amino acids, from approximately 7 amino acids to approximately 15 amino acids, from approximately 7 amino acids to approximately 10 amino acids, from approximately 7 amino acids to approximately 9 amino acids, from approximately 8 amino acids to approximately 100 amino acids, from approximately 8 amino acids to approximately 95 amino acids, from approximately 8 amino acids to approximately 90 amino acids, from approximately 8 amino acids to approximately 85 amino acids, from approximately 8 amino acids to approximately 80 amino acids, from approximately 8 amino acids to approximately 75 amino acids, from approximately 8 amino acids to approximately 70 amino acids, from approximately 8 amino acids to about 65 amino acids,from approximately 8 amino acids to approximately 60 amino acids, from approximately 8 amino acids to approximately 55 amino acids, from approximately 8 amino acids to approximately 50 amino acids, from approximately 8 amino acids to approximately 45 amino acids, from approximately 8 amino acids to approximately 40 amino acids, from approximately 8 amino acids to approximately 35 amino acids, from approximately 8 amino acids to approximately 30 amino acids, from approximately 8 amino acids to approximately 25 amino acids, from approximately 8 amino acids to approximately 20 amino acids, from approximately 8 amino acids to approximately 15 amino acids, from approximately 8 amino acids to approximately 10 amino acids, from approximately 10 amino acids to approximately 100 amino acids, from approximately 10 amino acids to approximately 95 amino acids, from approximately 10 amino acids to approximately 90 amino acids, from approximately 10 amino acids to approximately 85 amino acids, from approximately 10 amino acids to approximately 80 amino acids, from approximately 10 amino acids to approximately 75 amino acids, from approximately 10 amino acids to approximately 70 amino acids, from approximately 10 amino acids to approximately 65 amino acids,about 10 amino acids to about 60 amino acids, about 10 amino acids to about, Petition 870260061675, dated 06 / 23 / 2026, p. 67 / 935 60 / 362 amino acids, approximately 10 amino acids to approximately 50 amino acids, approximately 10 amino acids to approximately 45 amino acids, approximately 10 amino acids to approximately 40 amino acids, approximately 10 amino acids to approximately 35 amino acids, approximately 10 amino acids to approximately 30 amino acids, approximately 10 amino acids to approximately 25 amino acids, approximately 10 amino acids to approximately 20 amino acids, approximately 10 amino acids to approximately 15 amino acids, approximately 20 amino acids to approximately 100 amino acids, approximately 20 amino acids to approximately 95 amino acids, approximately 20 amino acids to approximately 90 amino acids, approximately 20 amino acids to approximately 85 amino acids, approximately 20 amino acids to approximately 80 amino acids, approximately 20 amino acids to approximately 75 amino acids, approximately 20 amino acids to approximately 70 amino acids, approximately 20 amino acids to approximately 65 amino acids, approximately 20 amino acids to approximately 60 amino acids, approximately 20 amino acids to approximately 55 amino acids, approximately 20 amino acids to approximately 50 amino acids,from approximately 20 amino acids to approximately 45 amino acids, from approximately 20 amino acids to approximately 40 amino acids, from approximately 20 amino acids to approximately 35 amino acids, from approximately 20 amino acids to approximately 30 amino acids, from approximately 20 amino acids to approximately 25 amino acids, from approximately 30 amino acids to approximately 100 amino acids, from approximately 30 amino acids to approximately 95 amino acids, from approximately 30 amino acids to approximately 90 amino acids, from approximately 30 amino acids to approximately 85 amino acids, from approximately 30 amino acids to approximately 80 amino acids, from approximately 30 amino acids to approximately 75 amino acids, from approximately 30 amino acids to approximately 70 amino acids, from approximately 30 amino acids to approximately 65 amino acids, from approximately 30 amino acids to approximately 60 amino acids, from approximately 30 amino acids to approximately 55 amino acids, from approximately 30 amino acids to approximately 50 amino acids, from approximately 30 amino acids to approximately 45 amino acids, from approximately 30 amino acids to about 40 amino acids, about 30 amino acids to about 35 amino acids,about 40 amino acids to about, Petition 870260061675, dated 06 / 23 / 2026, p. 68 / 935 61 / 362 of 100 amino acids, approximately 40 amino acids to approximately 95 amino acids, approximately 40 amino acids to approximately 90 amino acids, approximately 40 amino acids to approximately 85 amino acids, approximately 40 amino acids to approximately 80 amino acids, approximately 40 amino acids to approximately 75 amino acids, approximately 40 amino acids to approximately 70 amino acids, approximately 40 amino acids to approximately 65 amino acids, approximately 40 amino acids to approximately 60 amino acids, approximately 40 amino acids to approximately 55 amino acids, approximately 40 amino acids to approximately 50 amino acids, approximately 40 amino acids to approximately 45 amino acids, approximately 50 amino acids to approximately 100 amino acids, approximately 50 amino acids to approximately 95 amino acids, approximately 50 amino acids to approximately 90 amino acids, approximately 50 amino acids to approximately 85 amino acids, approximately 50 amino acids to approximately 80 amino acids, approximately 50 amino acids to about 75 amino acids, about 50 amino acids to about 70 amino acids, about 50 amino acids to about 65 amino acids,from approximately 50 amino acids to approximately 60 amino acids, from approximately 50 amino acids to approximately 55 amino acids, from approximately 60 amino acids to approximately 100 amino acids, from approximately 60 amino acids to approximately 95 amino acids, from approximately 60 amino acids to approximately 90 amino acids, from approximately 60 amino acids to approximately 85 amino acids, from approximately 60 amino acids to approximately 80 amino acids, from approximately 60 amino acids to approximately 75 amino acids, from approximately 60 amino acids to approximately 70 amino acids, from approximately 60 amino acids to approximately 65 amino acids, from approximately 70 amino acids to approximately 100 amino acids, from approximately 70 amino acids to approximately 95 amino acids, from approximately 70 amino acids to approximately 90 amino acids, from approximately 70 amino acids to approximately 85 amino acids, from approximately 70 amino acids to approximately 80 amino acids, from approximately 70 amino acids to approximately 75 amino acids, from approximately 80 amino acids to approximately 100 amino acids, from approximately 80 amino acids to approximately 95 amino acids, approximately 80 amino acids to approximately 90 amino acids, approximately 80 amino acids to, Petition 870260061675, dated 06 / 23 / 2026, p. 69 / 935 62 / 362 approximately 85 amino acids, approximately 90 amino acids to approximately 100 amino acids, approximately 90 amino acids to approximately 95 amino acids, or approximately 95 amino acids to approximately 100 amino acids removed from its N-terminal and / or 1 amino acid to 100 amino acids (or any of the subranges of this range described in this document) removed from its C-terminal.

[0055] In some embodiments, an active CLRN1 protein may, for example, include the sequence of a complete wild-type CLRN1 protein, wherein 1 amino acid to 50 amino acids, 1 amino acid to 45 amino acids, 1 amino acid to 40 amino acids, 1 amino acid to 35 amino acids, 1 amino acid to 30 amino acids, 1 amino acid to 25 amino acids, 1 amino acid to 20 amino acids, 1 amino acid to 15 amino acids, 1 amino acid to 10 amino acids, 1 amino acid to 9 amino acids, 1 amino acid to 8 amino acids, 1 amino acid to 7 amino acids, 1 amino acid to 6 amino acids, 1 amino acid to 5 amino acids, 1 amino acid to 4 amino acids, 1 amino acid to 3 amino acids, approximately 2 amino acids to 50 amino acids, approximately 2 amino acids to 45 amino acids, approximately 2 amino acids to 40 amino acids, approximately 2 amino acids to 35 amino acids, approximately 2 amino acids to 30 amino acids, about 2 amino acids to 25 amino acids, about 2 amino acids to 20 amino acids, about 2 amino acids to 15 amino acids,about 2 amino acids to 10 amino acids, about 2 amino acids to 9 amino acids, about 2 amino acids to 8 amino acids, about 2 amino acids to 7 amino acids, about 2 amino acids to 6 amino acids, about 2 amino acids to 5 amino acids, about 2 amino acids to 4 amino acids, about 3 amino acids to 50 amino acids, about 3 amino acids to 45 amino acids, about 3 amino acids to 40 amino acids, about 3 amino acids to 35 amino acids, about 3 amino acids to 30 amino acids, about 3 amino acids to 25 amino acids, about 3 amino acids to 20 amino acids, about 3 amino acids to 15 amino acids, Petition 870260061675, dated 06 / 23 / 2026, page 70 / 935 63 / 362 acids, approximately 3 amino acids to 10 amino acids, approximately 3 amino acids to 9 amino acids, approximately 3 amino acids to 8 amino acids, approximately 3 amino acids to 7 amino acids, approximately 3 amino acids to 6 amino acids, approximately 3 amino acids to 5 amino acids, approximately 4 amino acids to 50 amino acids, approximately 4 amino acids to 45 amino acids, approximately 4 amino acids to 40 amino acids, approximately 4 amino acids to 35 amino acids, approximately 4 amino acids to 30 amino acids, approximately 4 amino acids to 25 amino acids, approximately 4 amino acids to 20 amino acids, approximately 4 amino acids to 15 amino acids, approximately 4 amino acids to 10 amino acids, approximately 4 amino acids to 9 amino acids, approximately 4 amino acids to 8 amino acids, approximately 4 amino acids to 7 amino acids, approximately 4 amino acids to 6 amino acids, approximately 5 amino acids to 50 amino acids, approximately 5 amino acids to 45 amino acids, approximately 5 amino acids to 40 amino acids, approximately 5 amino acids to 35 amino acids, approximately 5 amino acids to 30 amino acids,approximately 5 to 25 amino acids, approximately 5 to 20 amino acids, approximately 5 to 15 amino acids, approximately 5 to 10 amino acids, approximately 5 to 9 amino acids, approximately 5 to 8 amino acids, approximately 5 to 7 amino acids, approximately 6 to 50 amino acids, approximately 6 to 45 amino acids, approximately 6 to 40 amino acids, approximately 6 to 35 amino acids, approximately 6 to 30 amino acids, approximately 6 to 25 amino acids, approximately 6 to 20 amino acids, approximately 6 to 15 amino acids, approximately 6 to 10 amino acids, approximately 6 to 9 amino acids, approximately 6 to 8 amino acids, approximately 7 to 50 amino acids, approximately 7 to 45 amino acids, approximately 7 to 40 amino acids, approximately 7 to 35 amino acids, approximately 7 to 30 amino acids, approximately 7 amino acids to 25 amino acids, approximately 7, Petition 870260061675, dated 06 / 23 / 2026, p. 71 / 935 64 / 362 amino acids to 20 amino acids, approximately 7 amino acids to 15 amino acids, approximately 7 amino acids to 10 amino acids, approximately 7 amino acids to 9 amino acids, approximately 8 amino acids to 50 amino acids, approximately 8 amino acids to 45 amino acids, approximately 8 amino acids to 40 amino acids, approximately 8 amino acids to 35 amino acids, approximately 8 amino acids to 30 amino acids, approximately 8 amino acids to 25 amino acids, approximately 8 amino acids to 20 amino acids, approximately 8 amino acids to 15 amino acids, approximately 8 amino acids to 10 amino acids, approximately 10 amino acids to 50 amino acids, approximately 10 amino acids to 45 amino acids, approximately 10 amino acids to 40 amino acids, approximately 10 amino acids to 35 amino acids, approximately 10 amino acids to 30 amino acids, approximately 10 amino acids to 25 amino acids, approximately 10 amino acids to 20 amino acids, approximately 10 amino acids to 15 amino acids, approximately 15 amino acids to 50 amino acids, approximately 15 amino acids to 45 amino acids, approximately 15 amino acids to 40 amino acids,approximately 15 to 35 amino acids, approximately 15 to 30 amino acids, approximately 15 to 25 amino acids, approximately 15 to 20 amino acids, approximately 20 to 50 amino acids, approximately 20 to 45 amino acids, approximately 20 to 40 amino acids, approximately 20 to 35 amino acids, approximately 20 to 30 amino acids, approximately 20 to 25 amino acids, approximately 25 to 50 amino acids, approximately 25 to 45 amino acids, approximately 25 to 40 amino acids, approximately 25 to 35 amino acids, approximately 25 to 30 amino acids, approximately 30 to 50 amino acids, approximately 30 to 45 amino acids, approximately 30 to 40 amino acids, approximately 30 to 35 amino acids, approximately 35 to 50 amino acids, approximately 35 amino acids to 45 amino acids, about 35 amino acids to 40 amino acids, about 40 amino acids to 50 amino acids, about 40, Petition 870260061675, dated 06 / 23 / 2026, p. 72 / 935 65 / 362 amino acids to 45 amino acids, or about 45 amino acids to about 50 amino acids, are inserted. In some examples, the 1 amino acid to 50 amino acids (or any subrange thereof) may be inserted as a contiguous sequence in the sequence of a complete wild-type protein. In some examples, the 1 amino acid to 50 amino acids (or any subrange thereof) are inserted at various non-contiguous locations in the sequence of a complete wild-type protein. As can be appreciated in the technique, the 1 amino acid to 50 amino acids may be inserted into a portion of the sequence of a complete wild-type protein that is not well conserved across species.

[0056] Unless otherwise defined, all technical and scientific terms used in this document have the same meaning as commonly understood by a person skilled in the art to which this invention pertains. Methods and materials are described in this document for use in the present invention; other suitable methods and materials known in the art may also be used. The materials, methods, and examples are illustrative only and are not intended to be a limiting factor. All publications, patent applications, patents, sequences, database entries, and other references mentioned in this document are incorporated by reference in their entirety. In case of conflict, this descriptive report, including definitions, shall serve as the basis for control.

[0057] Other features and advantages of the invention will become apparent from the following detailed description and figures, as well as the claims. BRIEF DESCRIPTION OF THE FIGURES

[0058] FIG. 1 is an illustrative schematic representation of a genetic map of a CLRN-1 vector (SEQ ID NO: 40; 3397 base pairs (bp)) that can be used in any of the present Petition 870260061675, dated 06 / 23 / 2026, p. 73 / 935 66 / 362 methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a CLRN1 isoform 1 (SEQ ID NO: 1), a T2A sequence (SEQ ID NO: 31), a CLRN1 isoform 2 (SEQ ID NO: 6), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0059] FIG. 2 is an illustrative schematic representation of a genetic map of a CLRN-2GFP vector (SEQ ID NO: 41; 4177 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a CLRN1 isoform 1 (SEQ ID NO: 1), a T2A sequence (SEQ ID NO: 31), a CLRN1 isoform 2 (SEQ ID NO: 6), a T2A sequence (SEQ ID NO: 31), an eGFP (SEQ ID NO: 32), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0060] FIG. 3 is an illustrative schematic representation of a genetic map of a CLRN-3 vector (SEQ ID NO: 42; 4607 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), 5'UTR-291, a CLRN1 isoform 1 (SEQ ID NO: 1), 3'UTR-1357 (SEQ ID NO: 36), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0061] FIG. 4 is an illustrative schematic representation of a genetic map of a CLRN-4 vector (SEQ ID NO: 43; 4796 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), and a CLRN1 isoform 1. Petition 870260061675, dated 06 / 23 / 2026, p. 74 / 935 67 / 362 (SEQ ID NO: 1), a T2A sequence (SEQ ID NO: 31), an isoform 2 of CLRN1 (SEQ ID NO: 6), 3'UTR-1406 (SEQ ID NO: 37), a poly(A) signal from bGH (SEQ ID NO: 20), and an ITR from AAV2.

[0062] FIG. 5 is an illustrative schematic representation of a genetic map of a pITR-CBA-5'UTR-tGFP-3'UTR vector (5026 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), 5'UTR-291, tGFP (SEQ ID NO: 19), 3'UTR-1595, a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0063] FIG. 6 is an illustrative schematic representation of a genetic map of a CLRN-6eGFP vector (SEQ ID NO: 44; 4756 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), eGFP (SEQ ID NO: 32), 3'UTR-1406 (SEQ ID NO: 37), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0064] FIG. 7 is an illustrative schematic representation of a genetic map of a pITR-CBA-3'UTR-600A (3982 bp) vector that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a CLRN1 isoform 1 (SEQ ID NO: 4), a T2A sequence (SEQ ID NO: 31), a CLRN1 isoform 2 (SEQ ID NO: 6), 3'UTR-600 (SEQ ID NO: 27), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0065] FIG. 8 is an exemplary schematic representation of a genetic map of a CLRN-8 vector (SEQ ID NO: 46; 3982 Petition 870260061675, dated 06 / 23 / 2026, p. 75 / 935 68 / 362 bp) that can be used in any of the present methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a CLRN1 isoform 1 (SEQ ID NO: 1), a T2A sequence (SEQ ID NO: 31), a CLRN1 isoform 2 (SEQ ID NO: 6), 3'UTR-600B (SEQ ID NO: 28), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0066] FIG. 9 is an illustrative schematic representation of a genetic map of a CLRN-9 vector (SEQ ID NO: 47; 3982 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a CLRN1 isoform 1 (SEQ ID NO: 1), a T2A sequence (SEQ ID NO: 31), a CLRN1 isoform 2 (SEQ ID NO: 6), 3'UTR-600C (SEQ ID NO: 29), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0067] FIG. 10 is an illustrative schematic representation of a genetic map of a CLRN-0 vector (SEQ ID NO: 39; 4732 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a CLRN1 isoform 1 (SEQ ID NO: 1), 3'UTR 1773 (SEQ ID NO: 15), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0068] FIG. 11 is an illustrative schematic representation of a genetic map of a CLRN-7eGFP vector (SEQ ID NO: 45; 3580 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a sequence of Petition 870260061675, dated 06 / 23 / 2026, p. 76 / 935 69 / 362 eGFP (SEQ ID NO: 32), a poly(A) signal from bGH (SEQ ID NO: 20), and an ITR from AAV2.

[0069] FIG. 12 is an illustrative schematic representation of a genetic map of a CLRN-10 (SEQ ID NO: 48; 3511 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a CLRN1 isoform 1 (SEQ ID NO: 4), an HA sequence (SEQ ID NO: 34), an FP sequence (SEQ ID NO: 30), a T2A sequence (SEQ ID NO: 31), a CLRN1 isoform 2 sequence (SEQ ID NO: 5), a 3x FLAG tag sequence (SEQ ID NO: 35), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0070] FIG. 13 is an illustrative schematic representation of a genetic map of a CLRN-10myc vector (SEQ ID NO: 49; 3574 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a CLRN1 isoform 1 (SEQ ID NO: 1), a myc sequence (SEQ ID NO: 33), an FP sequence (SEQ ID NO: 30), a T2A sequence (SEQ ID NO: 31), a 3x FLAG tag sequence (SEQ ID NO: 35), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0071] FIG. 14 is an illustrative schematic representation of a genetic map of a CLRN-10NF vector (SEQ ID NO: 50; 3499 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a CLRN1 isoform 1 (SEQ ID NO: 1), a T2A sequence (SEQ ID NO: 31), a Petition 870260061675, dated 06 / 23 / 2026, p. 77 / 935 70 / 362 sequence of HA (SEQ ID NO: 34), an isoform 2 of CLRN-1 (SEQ ID NO: 5), a 3x FLAG tag sequence (SEQ ID NO: 35), a poly(A) signal of bGH (SEQ ID NO: 20), and an ITR of AAV2.

[0072] FIG. 15 is an illustrative schematic representation of a genetic map of a CLRN-11 vector (SEQ ID NO: 51; 4908 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a CLRN1 isoform 1 (SEQ ID NO: 1), an HA sequence (SEQ ID NO: 34), an FP sequence (SEQ ID NO: 30), a T2A sequence (SEQ ID NO: 31), a CLRN-1 isoform 2 sequence (SEQ ID NO: 5), a 3x FLAG tag sequence (SEQ ID NO: 35), 3'UTR-1406 (SEQ ID NO: 37), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0073] FIG. 16 is an illustrative schematic representation of a genetic map of a CLRN-11myc vector (SEQ ID NO: 52; 4971 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a CLRN1 isoform 1 (SEQ ID NO: 1), a myc sequence (SEQ ID NO: 33), an FP sequence (SEQ ID NO: 30), a T2A sequence (SEQ ID NO: 31), a CLRN1 isoform 2 (SEQ ID NO: 5), a 3x FLAG tag sequence (SEQ ID NO: 35), 3'UTR-1406 (SEQ ID NO: 37), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0074] FIG. 17 is an illustrative schematic representation of a genetic map of a CLRN-11NF vector (SEQ ID NO: 53; 4896 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a β-actin promoter of Petition 870260061675, dated 06 / 23 / 2026, p. 78 / 935 71 / 362 chicken, a chimeric intron (SEQ ID NO: 16), an isoform 1 of CLRN1 (SEQ ID NO: 1), a sequence of HA (SEQ ID NO: 34), a sequence of T2A (SEQ ID NO: 31), an isoform 2 of CLRN1 (SEQ ID NO: 5), a 3x FLAG sequence (SEQ ID NO: 33), 3'UTR-1406 (SEQ ID NO: 37), a poly(A) signal of bGH (SEQ ID NO: 20) and an ITR of AAV2.

[0075] FIG. 18 is an illustrative schematic representation of a genetic map of a CLRN-12 vector (SEQ ID NO: 54; 4640 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a 5'UTR-291 sequence (SEQ ID NO: 12), a CLRN1 isoform 1 (SEQ ID NO: 1), an HA sequence (SEQ ID NO: 34), 3'UTR-1357 (SEQ ID NO: 36), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0076] FIG. Figure 19 is an illustrative schematic representation of a genetic map of a CLRN-13 vector (SEQ ID NO: 55; 4291 bp) that can be used in any of the methods described in this document.The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a CLRN1 isoform 4 (SEQ ID NO: 7), a 3x FLAG tag sequence (SEQ ID NO: 35), a T2A sequence (SEQ ID NO: 31), a CLRN1 isoform 1 (SEQ ID NO: 1), an HA sequence (SEQ ID NO: 34), 3'UTR-600 (SEQ ID NO: 27), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0077] FIG. 20 is an illustrative schematic representation of a genetic map of a CLRN-14 vector (SEQ ID NO: 56; 4192 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a po Petition 870260061675, dated 06 / 23 / 2026, p. 79 / 935 72 / 362 CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a CLRN1 isoform 4 (SEQ ID NO: 7), a T2A sequence (SEQ ID NO: 31), a CLRN1 isoform 1 (SEQ ID NO: 1), 3'UTR-600 (SEQ ID NO: 27), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0078] FIG. 21 is an illustrative schematic representation of a genetic map of a CLRN-15 vector (SEQ ID NO: 57; 3505 bpbp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a CLRN1 isoform 4 (SEQ ID NO: 7), a 3x FLAG tag sequence (SEQ ID NO: 35), 3'UTR-600 (SEQ ID NO: 27), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0079] FIG. 22 is an illustrative schematic representation of a genetic map of a CLRN-16 vector (SEQ ID NO: 58; 3439 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric intron (SEQ ID NO: 16), a CLRN1 isoform 4 (SEQ ID NO: 7), a 3'UTR-600 sequence (SEQ ID NO: 27), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0080] FIG. Figure 23 is an illustrative schematic representation of a genetic map of a CLRN-17 vector (SEQ ID NO: 59; 130 bp) that can be used in any of the methods described in this document.The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric sh-intron (SEQ ID NO: 26), 5'UTR-291 (SEQ ID NO: 12), a CLRN1 isoform 1 (SEQ ID NO: 1), an HA sequence (SEQ IS NO: 34), 3'UTR-1773 (SEQ ID NO: 15), a Petition plate 870260061675, dated 06 / 23 / 2026, p. 80 / 935. 73 / 362 li(A) of bGH (SEQ ID NO: 20) and an ITR of AAV2.

[0081] FIG. 24 is an illustrative schematic representation of a genetic map of a CLRN-18 vector (SEQ ID NO: 60; 4277 bp) that can be used in any of the methods described in this document. The vector includes an AAV2 ITR, a CMV enhancer (SEQ ID NO: 17), a chicken β-actin promoter, a chimeric sh-intron (SEQ ID NO: 26), a CLRN1 isoform 1 (SEQ ID NO: 1), 3'UTR-1773 (SEQ ID NO: 15), a bGH poly(A) signal (SEQ ID NO: 20), and an AAV2 ITR.

[0082] FIG. 25 is an immunoblot image of CLRN1 protein levels in HEK293FT cells transfected 48 hours after transfection using anti-HA and anti-FLAG antibodies. Lane 1 - PageRuler Plus Pre-stained; Lane 2 - CLRN-10 (denaturation at 37°C); Lane 3 - CLRN-11 (denaturation at 37°C); Lane 4 - CLRN-12 (denaturation at 37°C); Lane 5 - negative control; Lane 6 - CLRN-10 (denaturation at 56°C); Lane 7 - CLRN-11 (denaturation at 56°C); Lane 8 - CLRN-12 (denaturation at 56°C); Lane 9 - negative control. The CLRN-1 isoform protein is a glycosylated protein that frequently migrates as staining bands.

[0083] FIG. 26 is an immunoblot image of CLRN1 protein levels from HEK293FT cells transfected 48 hours after transfection using an anti-FLAG antibody. Lane 1 - PageRuler Plus Pre-stained; Lane 2 - CLRN-10; Lane 3 - CLRN-11; Lane 4 - CLRN12; Lane 5 - CLRN-13; Lane 6 - CLRN-15; Lane 7 - negative control

[0084] FIG. 27 is an immunoblot image of CLRN1 protein levels from HEK293FT cells transfected 48 hours after transfection using an anti-FLAG antibody. Lane 1 - PageRuler Plus Pre-stained; Lane 2 - CLRN-10; Lane 3 - CLRN-10NF; Lane 4 - CLRN-10myc; Lane 5 - CLRN-11NF; Lane 6 - CLRN-11myc; Lane 7 Petition 870260061675, dated 06 / 23 / 2026, page 81 / 935 74 / 362 - negative control. All samples were kept at room temperature.

[0085] FIG. 28 is an immunoblot image of CLRN1 protein levels from HEK293FT cells transfected 48 hours after transfection using an anti-myc antibody. Lane 1 - PageRuler Plus Pre-stained; Lane 2 - CLRN-10; Lane 3 - CLRN-10NF; Lane 4 - CLRN-10myc; Lane 5 - CLRN-11NF; Lane 6 - CLRN-11myc; Lane 7 - negative control.

[0086] FIG. 29 is an immunoblot image of CLRN1 protein levels harvested from HEK293FT cells transfected 48 hours after transfection using anti-HA and anti-FLAG antibodies. Lane 1 PageRuler Plus Pre-stained; Lane 2 - CLRN-13; Lane 3 - CLRN-10; Lane 4 - CLRN-10NF; Lane 5 - CLRN-10myc; Lane 6 - CLRN-11NF; Lane 7 - CLRN-11myc; Lane 8 - negative control.

[0087] FIG. 30 is an image of an immunoblot using anti-CLRN protein levels (EKIANYKEGTYVYKTQSEKY; SEQ ID NO: 38) of rabbit polyclonal antibody of CLRN1 isoform 1 harvested from HEK239FT cells transfected with plasmids described in this document 48 hours after transfection. Lane 1 - PageRuler Plus Pre-stained; Lane 2 - CLRN-10; Lane 3 - CLRN-1; Lane 4 - CLRN-2; Lane 5 - CLRN-3; Lane 6 - CLRN-4; Lane 7 - CLRN-8; Lane 8 - CLRN-9; Lane 9 - CLRN-10; Lane 10 - CLRN-11; Lane 11 - CLRN-12; Lane 12 - CLRN-13; Lane 13 - CLRN-14; Lane 14 - CLRN-15; Band 15 - CLRN-16; Band 16 - negative control; Band 17 - negative control.

[0088] FIG. 31 is an immunoblot image of CLRN1 protein levels harvested from HEK293FT cells transfected 48 hours after transfection using a rabbit polyclonal antiCLRN antibody. Lane 1 - PageRuler Plus Pre-stained; Lane 2 - Anc80-CLRN0; Lane 3 - Anc80-CLRN-0 +PNGase F; Lane 4 - Anc80-CLRN-3; Petition 870260061675, dated 06 / 23 / 2026, page 82 / 935 75 / 362 Band 5 - Anc80-CLRN-3 +PNGase F; Band 6 - Anc80-CLRN-6eGFP; Band 7 - Anc80-CLRN-6eGFP +PNGase F; Band 8 - Anc80-CLRN13; Band 9 - Anc80-CLRN-13 +PNGase F; Band 10 - no vector; Band 11 - no vector +PNGase F. The CLRN-1 isoform protein is a glycosylated protein that frequently migrates as blotchy bands (bands 2, 4, and 8). After treatment with PNGase F, the blotchy bands disappeared and changed to distinct bands (bands 3, 5, and 8).

[0089] FIG. 32 is a set of immunofluorescent images of HEK293FT cells transduced by AAVanc80-CLRN6eGFP taken 24 hours and 48 hours after transfection in MOI 8,41E+04 and MOI 2,53E+05, respectively.

[0090] FIG. 33 is a bar graph showing the relative expression of CLRN1 and GFP in HEK293FT cells transduced with AAVanc80-CLRN-6eGFP (at MOI 1.05E+05 and MOI 3.15E+05), AAVanc80-CLRN-0 (at MOI 8.23E+04 and MOI 2.47E+05), AAVanc80CLRN-3 (at MOI 8.41E+04 and MOI 2.53E+04) and AAVanc80-CLRN-13 (at MOI 8.33E+04 and MOI 2.50E+05), respectively.

[0091] FIG. 34 is a bar graph showing the relative expression of CLRN1 and GFP in P2 cochlear explants from WT mice infected for 16 hours with AAVanc80-CLRN-6eGFP (at MOI 2.0E+05), AAVanc80-CLRN-0 (at MOI 2.5E+05 and MOI 7.6E+0.5), AAVanc80-CLRN-3 (at MOI 2.0E+05 and 6.03E+05) and AAVanc80CLRN-13 (at MOI 2.0E+05 and MOI 6.0E+05), respectively.

[0092] FIG. 35 is a set of fluorescent images of P2 cochlear explants from WT mice infected for 72 hours with 1,3E10 AAVanc80-CLRN-0 VG / cochlea, 9,9E9 AAVanc80-CLRN-3 VG / cochlea and 1,0E10 AAVanc80-CLRN-13 VG / cochlea showing Myo7a and DAPI staining.

[0093] FIG. 36 is a set of fluorescent images of ex Petition 870260061675, dated 06 / 23 / 2026, p. 83 / 935 76 / 362 P2 cochlear cells from WT mice infected for 72 hours with 1E09 VG / cochlear AAV Anc80.CAG.eGFP.3'UTR showing staining with eGFP, Myo7a and DAPI. DETAILED DESCRIPTION

[0094] Deficiency or mutations in “clarin 1”, the protein encoded by the CLRN1 gene, cause hearing loss and vision loss. For example, mutations in CLRN1 lead to Usher syndrome type III and retinitis pigmentosa.

[0095] Compositions comprising at least two different nucleic acid vectors are provided in this document, wherein: each of the at least two different vectors comprises a coding sequence that encodes a different portion of a CLRN1 protein, each of the coded portions being at least 30 amino acid residues in length, wherein the amino acid sequence of each of the coded portions may optionally partially overlap with the amino acid sequence of a different coded portion; no single vector of the at least two different vectors encodes a complete CLRN1 protein; at least one of the coding sequences comprises a nucleotide sequence spanning two consecutive exons of CLRN1 genomic DNA and does not have an intronic sequence between the two consecutive exons;When introduced into a mammalian cell, the at least two different vectors undergo homologous recombination with each other, thus forming a recombined nucleic acid that encodes a complete CLRN1 protein.

[0096] Compositions comprising a single nucleic acid vector are provided in this document, wherein the vector comprises one or both of (i) a first coding sequence encoding a first isoform of the CLRN1 protein and (ii) a second coding sequence encoding a second protein isoform. Petition 870260061675, dated 06 / 23 / 2026, page 84 / 935 77 / 362 CLRN1, wherein one or both of the first and second coding sequences comprise a nucleotide sequence spanning two consecutive exons of CLRN1 genomic DNA and without an intronic sequence between the two consecutive introns.

[0097] Compositions comprising two different nucleic acid vectors are provided in this document, wherein: a first nucleic acid vector of the two different nucleic acid vectors comprises a promoter, a first coding sequence encoding an N-terminal portion of a CLRN1 protein positioned 3' from the promoter and a splice donor sequence positioned at the 3' end of the first coding sequence; and a second nucleic acid vector of the two different nucleic acid vectors comprises a splice acceptor sequence, a second coding sequence encoding a C-terminal portion of a CLRN1 protein positioned at the 3' end of the splice acceptor sequence and a polyadenylation signal sequence at the 3' end of the second coding sequence;where each of the encoded portions is at least 30 amino acid residues in length; where the amino acid sequences of the two encoded portions do not overlap with each other; where no single vector of the two different vectors encodes a complete CLRN1 protein; and when introduced into a mammalian cell, splicing occurs between the splice donor sequence and the splice acceptor sequence, thus forming a recombined nucleic acid that encodes a complete CLRN1 protein.

[0098] Compositions comprising two different nucleic acid vectors are provided in this document, wherein: a first nucleic acid vector of the two different nucleic acid vectors comprises a promoter, a first coding sequence that encodes Petition 870260061675, dated 06 / 23 / 2026, page 85 / 935 78 / 362 each comprises an N-terminal portion of a CLRN1 protein positioned 3' from the promoter, a splice donor sequence positioned at the 3' end of the first coding sequence, and a first detectable marker gene positioned 3' from the splice donor sequence; and a second nucleic acid vector of the two different nucleic acid vectors comprises a second detectable marker gene, a splice acceptor sequence positioned 3' from the second detectable marker gene, a second coding sequence encoding a C-terminal portion of a CLRN1 protein positioned at the 3' end of the splice acceptor sequence, and a polyadenylation signal sequence positioned at the 3' end of the second coding sequence; wherein each of the coding portions is at least 30 amino acid residues in length, wherein the amino acid sequences of the coding portions do not overlap with each other;where no single vector of the two different vectors encodes a complete CLRN1 protein; and when introduced into a mammalian cell, splicing occurs between the splice donor sequence and the splice acceptor sequence, thus forming a recombined nucleic acid that encodes a complete CLRN1 protein.

[0099] Also provided in this document are compositions that include two different nucleic acid vectors, wherein: a first nucleic acid vector of the two different nucleic acid vectors comprises a promoter, a first coding sequence encoding an N-terminal portion of a CLRN1 protein positioned 3' from the promoter, a splice donor sequence positioned at the 3' end of the first coding sequence, and a recombinogenic region of phage F1 positioned 3' from the splice donor sequence; and a second nucleic acid vector of the two different nucleic acid vectors comprises a recombinogenic region of phage F1, a splice acceptor sequence positioned 3' from the recombinogenic region of phage F1, a splice acceptor sequence positioned 3' from the N-terminal region of CLRN1, a splice acceptor sequence positioned 3' from the N-terminal region of CLRN1, a splice donor ... and a splice acceptor sequence positioned 3' Petition 870260061675, dated 06 / 23 / 2026, page 86 / 935 79 / 362 combinogenic phage F1, a second coding sequence encoding a C-terminal portion of a CLRN1 protein positioned at the 3' end of the splice acceptor sequence and a polyadenylation signal sequence positioned at the 3' end of the second coding sequence; wherein each of the two coding portions is at least 30 amino acid residues in length, wherein the amino acid sequences of the two coding portions do not overlap with each other; wherein no single vector of the two different vectors encodes a complete CLRN1 protein; and when introduced into a mammalian cell, splicing occurs between the splice donor sequence and the splice acceptor sequence, thus forming a recombined nucleic acid encoding a complete CLRN1 protein.

[00100] Methods are provided in this document which involve introducing into the cochlea of ​​a mammal a therapeutically effective amount of any of the compositions described in this document.

[00101] Methods for increasing the expression of a complete CLRN1 protein in a mammalian cell are provided in this document, including the introduction of any of the compositions described in this document into the mammalian cell.

[00102] This document provides methods for increasing the expression of a CLRN1 protein in an inner hair cell, an outer hair cell, or both in a mammalian cochlea, including: introducing a therapeutically effective amount of any of the compositions described in this document into the mammalian cochlea.

[00103] This document provides methods for increasing the expression of a complete CLRN1 protein in a mammalian eye, including: intraocular administration of a quantity te Petition 870260061675, dated 06 / 23 / 2026, page 87 / 935 80 / 362 rapeutically effective of any of the compositions described in this document in the mammalian eye.

[00104] This document provides methods for treating hearing loss in an individual identified as possessing a defective CLRN1 gene, which include: administering a therapeutically effective amount of any of the compositions described in this document into the individual's cochlea.

[00105] This document also provides methods for treating vision loss in an individual identified as possessing a defective CLRN1 gene, including: administering a therapeutically effective amount of any of the compositions described in this document into the individual's eye.

[00106] Additional non-limiting aspects of the compositions, kits and methods are described in this document and may be used in any combination without limitation. CLRN1

[00107] The CLRN1 gene encodes “clarin 1” (CLRN1), a protein that is expressed in hair cells of the inner ear (e.g., inner ear hair cells, outer ear hair cells) and in the retina.

[00108] The human CLRN1 gene is located on chromosome 3q25.1. It contains 7 exons spanning ~47 kilobases (kb) (Vastinsalo et al. (2011) Eur J Hum Genet 19(1): 30-35; NCBI Accession No. NG_009168.1).

[00109] Several mutations in the CLRN1 genes have been associated with Usher syndrome type III (e.g., Usher syndrome type IIIA (MIM#606397) (see, for example, Fields et al. (2002) Am J Hum Genet 71: 607-617 and Joensuu et al. (2001) Am J Hum Genet 69: 673-684) and retinitis pigmentosa (see, for example, Khan et al. (2011) Ophthalmology 118: 1444-1448). Petition 870260061675, dated 06 / 23 / 2026, p. 88 / 935 81 / 362 type III mutations were found predominantly in exon 3 of CLRN1. The deafness of Usher syndrome type III can be modeled by generating CLRN1-deficient mice (see, for example, Geng et al. (2017) Sci Rep 7(1): 13480). Exemplary mutations associated with CLRN1 in Usher syndrome type III include: T528G, M120K, M44K, N48K and C40G.

[00110] Exemplary mutations associated with CLRN1 with retinitis pigmentosa include L154W and P31L (see, for example, Khan et al. (2011) Ophthalmology 118: 1444-1448).

[00111] Additional exemplary mutations in a CLRN1 gene that have been detected in individuals with hearing loss and methods for sequencing a nucleic acid encoding CLRN1 are described in, for example, Fields et al. (2002) Am J Hum Genet 71: 607-617, Joensuu et al. (2001) Am J Hum Genet 69: 673-684, Adato et al. (2002) Europ J Hum Genet 10: 339-350, Aller et al. (2004) Clin Genet 66: 525-529. Methods for detecting mutations in a gene are well known in the art. Non-limiting examples of such techniques include: real-time polymerase chain reaction (RT-PCR), PCR, sequencing, Southern blotting, and Northern blotting.

[00112] An example of a wild-type human CLRN1 protein is or includes the sequence SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, and SEQ ID NO: 7. Non-limiting examples of nucleotide sequences encoding a wild-type CLRN1 protein are or include SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, and SEQ ID NO: 8.

[00113] In some embodiments of any of the compositions described in this document, the CLRN1 protein comprises a sequence that is at least 75% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least less than 99%) identical to Petition 870260061675, dated 06 / 23 / 2026, p. 89 / 935 82 / 362 SEQ ID NO: 1.

[00114] In some embodiments of any of the compositions described in this document, the CLRN1 protein comprises a sequence that is at least 75% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least less than 99%) identical to SEQ ID NO: 3.

[00115] In some embodiments of any of the compositions described in this document, the CLRN1 protein comprises a sequence that is at least 75% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%) identical to SEQ ID NO: 5.

[00116] In some embodiments of any of the compositions described in this document, the CLRN1 protein comprises a sequence that is at least 75% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least less than 99%) identical to SEQ ID NO: 7. Complete Human Wild-Type CLRN1 Protein Isoform D (SEQ ID NO: 1) MPSQQKKIIFCMAGVFSFACALGVVTALGTPLWIKATVLCKTGALLVN ASGQELDKFMGEMQYGLFHGEGVRQCGLGARPFRFSFFPDLLKAIP VSIHVNVILFSAILIVLTMVGTAFFMYNAFGKPFETLHGPLGLYLLSFIS VALWLPATRHQAQGSCGCLVMILFASEVKIHHLSEKIANYKEGTYVYK TQSEKYTTSFWVIFFCFFVHFLNGLLIRLAGFQFPFAKSKDAETTNVA ADLMY Petition 870260061675, dated 06 / 23 / 2026, pp. 90 / 935 83 / 362 cDNA of isoform D of Human Wild Type CLRN1 (SEQ ID NO: 2) atgccaagc caacagaaga aaatcatttt ttgcatggcc ggagtgttca gttttgcatg tgccctcgga gttgtgacag ccttggggac accgttgtgg atcaacagcccacccagct cagcacggag gctctgctcg tcaatgcctc agggcaggag ctggacaagt ttatgggtga aatgcagtac gggctttttcc acggagaggg tgtgaggcag tgtgggttgg gagcaaggcc ctttcggttc tcattttttc cagatttgct caaagcaatc ccagtgagca tccacgtcagtcagtcttcttcgtcgtc gttaaccatg gtggggacag ccttcttcat gtacaatgct tttggaaaac cttttgaaac tctgcatggt cccctagggc tgtacctttt gagcttcatt tcagttgccc tttggctgcc agctaccagg caccaggctc aaggctcctg tgctgctgt gtcattgattgatt t atccatcacc tctcagaaaa aattgcaaat tataaagaag ggacttatgt ctacaaaacg caaagtgaaa aataccac ctcattctgg gtcattttct tttgcttttt tgttcatttt ctgaatgggc tcctaatacg acttgctgga tttcagttcc cttttgcagataga g tgcagatcta atgtactga Full-length Wild-Type Human CLRN1 Protein Isoform A (SEQ ID NO: 3) MPSQQKKIIFCMAGVFSFACALGVVTALGTPLWIKATVLCKTGALLVN ASGQELDKFMGEMQYGLFHGEGVRQCGLGARPFRFSFFPDLLKAIP VSIHVNVILFSAILIVLTTMVGTAFFMYNAFGKPPFETLHGPLGLYLLSFIS GSCGCLVMILFASEVKIHHLSEKIANYKEGTYKTQSEKYTTSFWVIF FCFFVHFLNGLLIRLAGFQFPFAKS KDAETTNVAADLMY cDNA from isoform A of CLRN1 Humana do Tipo Selvagem (SEQ ID NO: 4) atgccaagc caacagaat acatcatt ttgggatt ttgggca gttttgcatg tgccctcgga gttgtgacag ccttggggac accgttgtgg atcaaagcca ctgtcctctg caaaacggga gctctgctcg tcaatgcctc agggcaggag ctggacaagt tttgggtga aatgcagtac gggcttttcc acggagaggg tgtgaggcg tgtc ctttcggttc tcatttgtc cagatttgct caaagcaatc ccagtgagca tccacgtcaa tgtcattctc ttctctgcca tccttattgt gttaaccatg gtggggacag ccttcttcat gtacaatgct tttggaaaac cttttgaaac tctgcatggt cccttaggttc tgcttgt tcagcatt Petition 870260061675, of 23 / 06 / 2026, p. 91 / 935 84 / 362 ctcct gtggctgtct tgtcatgata ttgtttgcct ctgaagtgaa aatccatcac ctctcagaaa aaattgcaaa ttataaagaa gggacttatg tctacaaaac gcaaagtgaa aaatatacca cctcattctg ggtcattttc tttgcttct tctctgataggttc gacttgctgg atttcagttc ccttttgcaa aatctaaaga cgcagaaaca actaatgtag ctgcagatct aatgtactga C Isoform of Full Wild-Type Human CLRN1 Protein (SEQ ID NO: 5) MQALQQQPVFPDLLKAIPVSIHVNVILFSAILIVL™VGTAFFMYNAFG KPFETLHGPLGLYLLSFISGSCGCLVMILFASEVKIHHLSEKIANYKEG TYVY KTQSEKYTTSFWLTKGHS cDNA to isoform C to CLRN1 Human do Type SEQ: ID: ID: NO cctgcagcag caaccagttt ttccagattt gctcaaagca atcccagtga gcatccacgt caatgtcatt ctcttctctg ccatccttat tgtgttaacc atggtgggga cagccttctt catgtacaat gcttttggaa aaccttttga aactctgcat ggtcccctag ggctctct ttgaggtc cctgtggctg tcttgtcatg atattgtttg cctctgaagt gaaaatccat cacctctcag aaaaaattgc aaattataaa gaagggactt atgtctacaa aacgcaaagt gaaaaatata ccacctcatt ctggctgact aaaggccaca gctga Full-length Wild-Type Human CLRN1 Protein Isoform E (SEQ ID NO: 7) MPSQQKKIIFCMAGVFSFACALGVVTALGTPLWIKATVLCKTGALLVN ASGQELDKFMGEMQYGLFHGEGVRQCGLGARPFRFSCYFLDPFMG LPTGVPHLLSLPCSTSCRREHTSERVQEPAGCFSAVRSKLHAGPAAA TSFSRFAQSNPSPRSEHQQQ LLCHPYCVNHGGDSLLHVQCFWKTF cDNA of isoform E of Wild Type Human CLRN1 (SEQ ID NO: 8) atgccaagc caacagaaga aaatcattttt ttgcatggcc ggagtgttca gttttgcatg tgccctcgga gttgtgacag ccttgggga accgttcgtcgtcggt caaaacggga gctctgctcg tcaatgcctc agggcaggag ctggacaagt ttatgggtga aatgcagtac gggcttttcc acggagaggg tgtgaggcag tgtgggttgg gagcaaggcc Petition 870260061675, of 23 / 06 / 2026, p. 92 / 935 85 / 362 ctttcggttc tcatgctatt ttcttgaccc cttcatggga ctcccaacag gggtacccca tttactcagc ctgccctgct caacctcttg caggagggag cacacgagtg aacgagtgca ggaaccagct ggctgcttta gtgctgtgag gagtaaactc catgcaggcc ctgcagcagc aaccagtttt tccagatttg ctcaaagcaa tcccagtgag catccacgtc aatgtcattc tcttctctgc catccttatt gtgttaacca tggtggggac agccttcttc atgtacaatg cttttggaaa accttttga Genomic Sequence of CLRN1 Humana do Tipo Selvagem (SEQ ID NO: 9) aggagatact tgaaggcagt ttgaaagact tgttttacag attcttagtc caaagatttc 61 caattaggga gaagaagcag cagaaaagga gaaaagccaa gtatgagtga 121 gacatttacttac ctggcgagaa ccgtcgatgg tgaagttgcc tttcagctg 181 ggagctgtcc gttcagcttc cgtaataaat gcagtcaaag aggcagtccc ttcccattgc 241 tcacaaaggt cttgtttttg aacctcgccc tcacagaagc cgttcatc aaatcattt ttgcatggcc ggagtgttca gttttgcatg tgccctcgga 361 gttgtgacag ccttggggac accgttgtgg atcaaagcca ctgtcctctg caaaacggga 421 gctctgctcg tcaatgcctc agggcaggag ctggacaagt acggagaggg tgtgaggcag tgtgggttgg gagcaaggcc ctttcggttc 541 tcatgtaagt agcaattgca tttgagttat ttaatgcttt aggcagactc ttcccagtgt 601 tgcgaggaat tatatttgag aattttgccg tgtttactgc aggacttgc aggtatc616 aaaaacctat gactctgagc aatttcttct tcctagtttt tattatttta 721 tacttgcttt ttattataat atagagttaa ttcattgtta cataattaag gtttttggaa 781 atattggcaa ttaagatgcttaagtattaa tatttatgta aaaaaattatg gagtctttt 841 aaaaaagtaa acttggggaa ataggaaagc tgtaaagaat gatctttatg cttttgttc 901 tttataaaaa gaaccaaggt catgggctcc gtatttaacc aggttgccac ctttctcatg 961 attttgtttc ctgctcccca ctccctccca ttattcctgc taagaccttt cctgctgcta 1021 aatattcagt tttcatttt aactaatttg gaatcatttg gctatagaaaa tttaaaaatga 1081 tctgctgtgc taactgggaa agaaatggat gcctatttag tatagaacat tttaaactga 1141 ttgacctgca aatcatgtag agaatatgag agagattttc ttgttgtgat tttgtgaaa 1201 tggaagtgta atccacagta tttataacct gtttatctta agaagagaat ttttaaaaaat 1261 taccatgtga ataggcaact cattaaatga aaattaatag gaagtcattt Petition 870260061675, de 23 / 06 / 2026, pág. 93 / 935 86 / 362 gttatatctc 1321 ttacaacaca cattcagaag ttattattat ttcagaaggg ctggtttgga acaaccttat 1381 gaagacacag tcagtaaatt actgcataaa tcactcttca ggaaaggagg ttaccaactg 1441 aagcat gaatcgatt taggtt attattc tttctttcta gtataggtag 1501 aaggctaaat taattgaatt tattattaac atatgcagtg cctaattaaa tttcagtgct 1561 ggtctattta tatttctgca acattcctta tatcttctta gcagtcattg gacaccaacc 1621 ttcagctcac aaattccaa 1681 gaattggttg ttagcttttt aattgatgaa gtggatacca gttcttttca ctgaatggct 1741 tttattcatt aaggtaatgg ggctgttaga gttgcttagt tttcctgggg aaggggaagg 1801 aagaaaacaaat cagcacgactagtat aaaaggaaaa 1861 aagttgagag agatgattta accgtgagtc accggcagcc aaagcgtgag taaagcttct 1921 cacagatgaa tttagacaaa agcggagaag gtactggtga attttctgga gcctttacat 1981 tttctacagt gaaatttac caaaacaata 2041 ataagatgtt ttctgaacac ttactacata ctaagcactt tatatgcttt gtctcattta 2101 atccttacac agccacattc ttctggggtt tagcgaatga ttttgtggttgtgtcctat 2161 gcttgtcctg tctaaggatg aagttgttct aattgggtgc ccctcctttt gctttctgtg 2221 aggacttgca gaactggtgg ggtttaaaca gtaccctcac ttatctcaca gaatttcatt 2281 agctcccaga taccctcctctt aagaaaatct tccatttact 2341 tgttcattct gcagtgacag ctccatcaat atacaataga ctatacatat taagtgtact 2401 gtatatacta tacatgttaa aaatctcatt cattttggtg aggcccagct aagaatactt 2461 acagtagttagc ttttagttca ttcatatc ttcatatc ttcaatt cagcatgaga 2521 cagagttggg aaaaccaaaa taaatagatc caatggactc cccaaagagg ataatattca 2581 tttaaataaa cacccctc agtgttaaaa cttctaatc aacatgcctt tgggacacat 2641 tgcaccctca acccatttaca tcagcttc gtggttcacg ttttttccat 2701 tcagaatgtc attaccctgt caatgatgtt tcatcaacgt ttgcttggat gagaatcctc 2761 tgatattctt cctgatagaa atgtataagc cctgttcata taaatgaata aaagatctaa 2821 ccttagttc tcacc gggacctcca gagagctcag 2881 gtggatgact cttttctgtt tcttccagag ctcaacttac aattagtgca caattcattt 2941 cccagaatgt cttctttctt attgtgcctt tagaaagtta ttaagcaaacatttgaattc 3001 acagaatctt accagtgtaa gaggaatgga aaaggtaact tatcaaggta acaatcactt 3061 Petition 870260061675, of 23 / 06 / 2026, p. 94 / 935 87 / 362 cgtggccagt tttcggct cactgcaact acccctcctg ggttcaagcg attctcctgc 3121 ctcagcctcc caagtagctg ggaccagc taatttt 31tt8ctt1 tattgttagacc aggctggtct catggcaagt 3241 tttcttgtg ttgtcatgtt atttacaatt ataggaatt tatattcag ttctgttagg 3301 tggataaca ctatttgca tacctaatg ttcatttat gccagcactg gccataaaa 3361 acctaggctt agcagcactt tgcataaa aatcccaact tttgggaggc 3421 caacacttg ggaggacaca gggtcaggag atcgagacca tcctggctaa cctggtgaaa 3481 tcccgtct actaaaaata caaaaatta gccggcgtg gcgggggcgc aggtt5gggaggtcc gcacgaaccc gggaggtgga gcttgcagtg 3601 agccgagatc tcgccactgc actcagcct tggtgacaga gcagactct gtctcaaaaa 3661 aaaaaaaaa aaaaaaaaa aaaaatata tatata2tagtacca atatagcattaaccattac gtcctagtag ccatattaga aaacaaagt aaaaaggaat 3781 agatgaaatt aattttaatg atttttttaa acccaagata tccaaaatat tatcatttta 3841 acatataatt aaaaatttat tgagatgttt tacattgtt ttttttgtt1 tcgcgt 3781ttggaaatct agagtgtatt ttacatttac attacatcta attcagtcta gccacatttc 3961 acatgctcat ttttttgtgt gtggttttat ggagcagaga gtttaatagg caagaaagaa 4021 aagagaaggc agaagaaaat ggctcccctg tacagagacg cgggtc gccaaaagag gaggtcccta agtatggtag acaccagcca ggaatatatg cagtgtctgg 4141 aggaggggat gtctgatttg catagggtca catgctcatt tttatggcta ctgtattggt 4201 cagtacagat ttagatgggg atttgctctg aacaagttgg tgattgt 416 ttttcctggg ttctgctgta cacttgtatg tgtgttagtt tcatgtgcaa 4321 tgcttgtgtc acttttaaaa cccagatata tggcataaca tgagaatgaa aaatggacca 4381 gaaaaatagt ttggcaatgt agtcatgttt gttcctatta aatgttccct atctact4 aagaatctgc cctgccagca tgcccagtta cgctgggaaaa 4501 acttctgcct catttactct ggctgattct catccactta tgggtcagtg gttcattttc 4561 tagaggtcac cagcattcat acctagcata caatttcatt cattataattg aaggaattg2466tccacaa aga ctagtgggct taatttttct tgatatgtca cctgtaaaat 4681 tttaatgatg atgtttaaac tctaaatgta gccatcaaga caaaaactgc aaatttgag 4741cctcagtgtg tgtgggtggg tttctgtttc ggtaatttga aacattgcag aatatcatca 4801 aaatatgata Petition 870260061675, dated 06 / 23 / 2026, pages 95 / 935 88 / 362 cccaagaatc atatggtatc aatcattcct agatatactg atctattcat 4861 tgccaagata gttcaatgag ctggcaaaaa catatggaat tattttctta aaatgtgaaa 4921 aataaaattt aaccaatcat gtatcacagc ttgcacacttt agtcactt tgacat 4981 tttaatttgg acctcatgat tgaaaattta taaaaagctg aacagaaatt agttcacttc 5041 atattttaga aaagcagagt ttctttacta aatgaggcat ttgacccaaa ttggagagaa 5101 aatgttgaaa ctacttctgt gagcaagcag gtggcttc aggacacata 51616 tggttgggcc tcagggtctc agtgcctgtc actgagagtt ggcactctct atctccatgg 5221 tctcctccaa gtgtgactct tgtctcttgc tgacctgacc tgccccaagt gactcactgg 5281 tcatgaccct gcacaccttg cgtcctccct gtcac 5341 tctttgatgt agctctgtct gatatcctgt gtttccccct atggtctgtg tggaagcagg 5401 tatgggggtg tgtaaagggg aagcctatga agttcatctg caaagactac ctggttaggg 5461 gaggagagga agaagctata tgcaccattt caccagcagct cacggct t552 agcttagggg tcctgttgtc tagtctcact cacctattaa aacagtccag caatagagg 5581 ttttgtttac ctcccattaa aaaaaaagca attaatggaa tagaagataa taatgtatga 5641 gaagcactattgtgaaagaa aaaccttcaa cttctctcag ccaaataatt gcttcctcct 5701 ctgtccttcc cagaccttga tgtttgctct attatttcaa aacaactata ttataaatat 5761 ttgagaatgt gtatttccct gcaaggagat cttaatcccc aagaagggcagcgcgta 8585 cagtgctcct tcaaaccagg gcctcagaca gtgcatggcc caaagaggta 5881 cttaataaac gtttggtaaa ctgacactat tgaaatttaag caacctggat ttgaggtggg 5941 tctctgccac tcacaagaga ttacgctttg agaaaattcc atcattct tcattc tgtatatggg agacgatact aggtgatttc tgacatctct caccgtttaa 6061 atgctctgtg atctatacaa cgaggggctc gctgttctag acaagttcct tccagcttta 6121 cagttgcata acccttctaa tcttagtcac atgatgactc cactgactc ttgatcttgcatgcatgcatg1818 ttacgtgtgc ctttgctctg atcctcaaaa ctcatgattt 6241 ttaaagtttt ctgaaatatc taccatttat caggatccag atggatttca tgaccaaagt 6301 ggatgtttct tttctctccc attacaatct tttacttttt gtgtggggaaa ttgcatc tgggatgctt tggaattctg gcaagatgga ttagtgggtt 6421 ccagaaagta ggggcagcca caaataccga aataaatgag atcgtattat tgagaaagca 6481 caaatggaagaaggtcaaaa gcaagaagaa gctgacatcc tgcttcctcc aatttttgct 6541 ttctctgttt Petition 870260061675, dated 06 / 23 / 2026, pp. 96 / 935 89 / 362 ttccaagaaa ctcctcttcc aagccttgct gaaaaactcc actttcctaa 6601 atctaacttc ttaaactgat aatggcaaga agttaggaat gaccaatatg tttaacactc 6661 caagagtatt tgtttgttt tgtttgaga ctgggtctca ctctgtcgtc cagcctggag 6721 tgcagtggtg tgatcacagc tcactgcagc cttgacctct cctgcccaag gaatcctccc 6781 acctcagcct cctgagtaga agggaccaca ggcatgtgcc actacacctg gctaacttt 6841 aaaaaatttt tttgtagaga tggggttgcc caggcaggtc tcaaactgct gggctcaagc 6901 aatcctcctg cattggcctc ccaaagtgct ggaattatgg gcataagcca ctacgcctga 6961 cctctccaag ggcattcttt acccaagaga ggaacttggc agaacttatc ctccaattgg 7021 tgaggaatat ggagaaaatg actttaagca areaacttc tggttctgcc tacctaatcc 7081 agaaaagaa gttttatttc tcccttcccc tagtaactat cttcccatat tcacataaaa 7141 areagaa tcaacattgt tcaagaatta taattttact tgtaagcaca tgtgcacacg 7201 cacaccata taccttcctt ccctttaaat catcccacac cctaatagta gtaaaatcat 7261 tgacccgagc atacctggga gaggaagagg agtctgacag gggcaggttc taagtggcac 7321 tcctggaact taaccctggt gtatatgaac tttacctatt gaaggatgac tcctcaactg 7381 ttctcacaatttgctgctct gctttcttt ctaatttctg aaggtgactc atcttcccca 7441 aggactttca gacttctcag aagaaaaaaa tattgggtgg gtctctgcca ctggcaaaag 7501 attagacttt gagaatcata aaagtatatc agttatact cattata aataattaat 756 gaatttaat atgatattga tataatgata gaatgatatt gataaaagca atattcaata 7621 atgaatatta tttcagctgc ccacttattg ggtgcctcat aggtgccagg cattttgtat 7681 gtattatcta caacccttac atgggacata ttatgatgct gtttctcttg aagaaattg 7741 acagaagaaggatg caccacaatt ttccaaagtc acatagctaa taggtagcag 7801 acttgggatt caaattcata tgcatatggt aaatcatgct cttcctctgc tacattttgc 7861 ccccttagaa tatgaaaaag ggatacaaag agatgaagaa aatatgtaag attatccttcttc 7921 aattcttactactacta agtttttttt attatacttt aaattctgaa atacatgtgc 7981 agaacatgca ggtttgttac ataggtatac acgtgccatg atggtttgtt gcacccatca 8041 acctgtcatc tacattaggt atttttccta atgctatccc tcccctagtc ccccacccac 811agcccgcgttc cggtc cctgtgtcca tgtgttctca ttgttcaact 8161 cccacttatg agtgagaaca tgcggtgttt ggttttctgt tcctgcgtca gtttgctgag 8221 aatgatggtttccagcttca ttcatgttcc tgcaaaaggc atgaactcat tttatggctg 8281 Petition 870260061675, dated 06 / 23 / 2026, pp. 97 / 935 90 / 362 cataccattc tatggtatac atgtgccaca ttttcttaat ctagtctatc attgatgggc 8341 atttggctta gttccaagtc cttgctattg tgaacagtgc tgcaataaac atatgtgggc 8401 atatgtcttt atagtagaat gatttataat cctttgggta tagacccagt aatgggattg 8461 ctgggtcaaa tggcatttct ggttctaggt ccttcaggaa ttgccacact gtcttccaca 8521 atagctgaac tagtttacac tcccaccaac agtgtaaaag cgttcctatt tctccacatc 8581 ctctccaaca tctgttgctt cctgactttt taatgattgc cattctaatt ggagtgagat 8641 ggtatctcag tgtggttttg attagcattt ctttaatgac aagtgatgat gagctttttt 8701 tcatgtttgt tggccgtata aatgtcttct tttgagaagt gtccgttcat atcctttgcc 8761 cactttttaa cggggttttt tcttgtaaat ttgtttaact tccttgtaga ttctggatat 8821 tagtcctttg tcagatgggt agattgcaaa aattttcttc cattctgcag gttgcccgtt 8881 cactctgata atagtttctt ttgctgcgca gaagtttttt tagtttaatt agatcccatt 8941 tgtcaatttt ggcttttgtt gccattgctt ttggtgttta gtcatgaagt ctttgcccac 9001 gcctatgtcc tgaatggtaa tgcctaggtt ttcttctagg atttttatgg ttttaggtct 9061 tatgtttaaa tctttaatcc atcttgagtt aatttttgta taaggtataa ggaaggggtc 9121cagtttagtt ttctgcatat ggctagccag ttttcccaac accatttatt aaatagggaa 9181 tcctttcccc gttgcttgtt tttgtcaggt ttgtcaaaga gcagatggtt gtagatgtgt 9241 ggcattattt ctgaggcctc tgttctgttt cattggtctc tgtatctgtt ttgatacaag 9301 taccatgctg ttttggttac tgtagacttg tagtataatt tgaagtcagg tagcgtaata 9361 cctccagttt tgttcttttt gcttaggatt gtcttgacta ttcaggctct tttttggttc 9421 catatgaaat ttaaagtagt tttttctaat tctgtgaaga aagtcaatgg tagcttgatg 9481 ggaaaagcat tgaatctata agttactttg ggcagtatgg ccattttcat gatattaatt 9541 cttcctatcc gtgagcatgg aatgtttttc catttgtttg tgtcctttct tatttccttg 9601 agcagtagtt tgtagttctc cttgaagagg tccatcacat cccttgtaag ttgtattcct 9661 aggtattttg ttctctttgt agcaattgtg aatggaagtt cactcataag tttgctctct 9721 gtttgtctgt tattggtgta taggaatgct tgtgattttt gcacattgat tttgtatcct 9781 gagactttgc cgaagttgct tatcagctta aggagatttt gggctgagac gacagggttt 9841 tctaaatata caatcatctc atctgcaaac agagacaatt tgacttcctc tcttcctatt 9901 tgaatacgct ttatttcttt ctcttgcctg tttgccctgg ccagaacttc caatactgtg 9961ttgaatagga gtgttcacca cctattttaa gaatagtatt gaagcctcac aaaagctggt 10021 tctcatgtaa ccatctgaga atatttggcc ttatgacttg aattcattca ttgccttttt 10081 atttcacatt ttagtgatcc Petition 870260061675, dated 06 / 23 / 2026, pages 98 / 935 91 / 362 tgatgtctaa atcttaatct ttgatccttg caaggtaaaaaa 10141 tagccaagtc aagcctgttt aataatattg gttgaggaag tcacatgctt atgatcaatc 10201 tttgggttat gtaattatat taccttaatg ttggcagttt aggtggtac tgatcagattac1 tgtggttagc taatttaaga tcactgccaa ctaaaatctt catggtatga 10321 tcttcaaagt tagctacttt gaccacagca atgatttcac cacagcaatt aacaaaatgg 10381 cagactcttt cctgaggtgg catgaacagt tttaaaacaa agcaaaaaa 1044a gcaggcacat ggcatttgat tcatttcaaa aactagtatt gtattaagag ccaaggggat 10501 agaattgtag catcaattaa aatcttgttt gaaaaaaaat aaaaacaaac gtccattttt 10561 atctctcaaa tatattaggg tttcattaaaa gttacagttacaa tattacaaa 10621 tcatatacat tagactgaaa aatttgcctg tcatctcatc atgcagctaa atgcaattgt 10681 ctatggcgag atacactctt attagaggta tgatagcact aactaatagc aaactttgta 10741 cctggtagtc aggg taattttgc ttcactcctcgcctcgc ctgtaactgt 10801 ggcaaagcca ttctcaggag ttattacccc aacataatca tacccctgtg gattaggagc 10861 agttaaatgg gtcctgttat cagagacaca tatgtgccac agccgctgtc atccctaagc 10921caccgtgggt gattaagact cactgatggg actacctctg aataggcttg agtgaggtgg 10981 atacacttca gctgagagaa attcaggtaa ggggctgaga aaatcagatt ttgaatggtt 11041 ttatcatacc atcaggtctc cttttaagtg ctggggtcat ggatttcatt caacctgacc 11101 acatagcctt tggaagcttg gctcaatacc tgagtgtgag attatgggtg atattaaagg 11161 agatgaatgc attgagctga tgtcagagaa tgtcttttac tggattttca taatgactgg 11221 ctgcagatgg gctgagggga aagtcagatc aagagcattt ctgtaagaag aaagaaatct 11281 tccctcttat tctctttcaa gaaaatgaat agctgagcac caagaggcca aatactttt 11341 taaaaaacac atcctttat gtagagaagg acaggttgag acgaaaaaca ggacctctga 11401 aactgtcttt atagctttaa tctaggaaga aattgcggca ccattgctga catcattatc 11461 agaggctgcc ttagttctga gagcttcaca gatggccttt tctgcattt acatctggcc 11521 agatgaaggc aaaaaggttg atgaaaccaa aactattaga tcagtggtcc ataactctgg 11581 ctgcacttta gaatcatctg gggagtcctt aaaactactg atcctgaggc tccatcccag 11641 accaattgaa tcaggatctc tgggggtggg acctgagcat tggaatgctt taaaagttcc 11701 tcaggactc taatgtgcag ccaaggctga gaatgactga ggtggtggggccaagaca 11761 ggtgaggcca agagttagaa Petition 870260061675, dated 06 / 23 / 2026, pp. 99 / 935 92 / 362 gcccttactg ttagggaagg cagaagccac aaggaggagg 11821 ggagggggaa ggagcagtat ttagcatttc ttccacacag ttggggggtt ttctgatcaa 11881 aattaggctg ggatctttcg cttccattt catgaaggtc ttatgctttg tccacagcca 11941 cctggcctca gggcaatgag caatctgatt gatgaatttt cagataagaaa ctgagcacac 12001 ttggctctca gccccagtgg cttcccctgt ttccaaatct gcccaccagt tacaggagcc 12061 tgctcaccaa ctggttgggt taaagaagtc ggctctgtcc ttggcaggga ggccttcagc 12121 tgtctggccc tgtctgtgac tgcgtgggtg aagctgccta atttggggaa cttgatggaa 12181 gatctaagct atgttctcta acagttttat cagaataaa gttaactttt gacctccatc 12241 tgcctgtctc ctgtggaagg gctctgctcc ttccaaagag actctcaggg gttctcctta 12301 gaggtgtgtt atcagtccaa agatcatttt agaccagcca ttacagagga tgtccaagaa 12361 attgcacaag ggaataagaa gtaagaatga gagcaata tcagatagta aggaaagtt 12421 gtgactggtt tcaaataagt aattaaccat aaatccaaag ttcctgcatt agttatagca 12481 atagtcatcc acctggtcag gaaaaaaaaa gtaaaagact gagctgcaag atagaaagtt 12541 tgcctgaatt ccaagtactt caaggactac tatggaggat tccttggtcc caatgcagag 12601acatgtactc tgaccaccca tgggccaat ccctcttacc caccctcagt gattcctcct 12661 gggacctcac tacattgagt tcttacattc cccactt tcggggaaa tataacctt 12721 ctgctctct catcattat gatacatta aaattact 12781 cacataaatg tgtttcttgt gagctctgtg atttattctt atttacatct 12841 atgctgatg ttaggaaac tgagatatcg agaccacat gcatagtaaa tggcaaaacc 12901 agatgaattt agtaccaccacttacc gccatgctgc 12961 cgctcagtta atgcctggct gttgtctcc ccattgccc cttacccat tgtgctttga 13021 tgcacactg tattcact gcctgagact cctggttaat gccattacgt acggacttag gttgattagag 13081 atatgactgt tagactggaa 13141 tcagcatag aaaaggtt aaaaagtttt cagataaaa tataatagaa aacccagca 13201 gatagaagta aaatgaatgg taagacaaag ccatacattt agaataatca 13261 atacatacaataaggaattaacacac gtaaaaacac 13321 tttttacctt attcttatta ccctccagta accttttt tttttttt tgagacaaag 13381 tctcgctgtg tcgtccaggc tggaggtag tgatgtgatc tcggctcactgcaacttctg 13441 cctcttgggc tgaaga Petition 870260061675, dated 06 / 23 / 2026, p. 100 / 935 93 / 362 gatt ctcctgcccc agcctcctga gtagctggga ctataggggc 13501 ccatcactgc acctggctaa tttttgtatt tttagtag acggggttc accatgttgg 13561 ccaggctggt cttgaactcc tggcctcagg tgatccaccc gcctcagcct cccaaagtgc 13621 tgagattaca agcgtgagcc accaagcccg gctgtaacct attgaaata acattacttg 13681 acatgtgaga caaattttt gtaagttaaa gagtttatgt gccttcaatg ctcccaccct 13741 tccctcccct aaaaagatta ttgagtgccc atgatgtgcc taagccttct ggtagactct 13801 gagaatgtga agagagttag aggatacttg ttcaacaacc cagaatctag cagaagtgtt 13861 ttgaaatgac cagccacttg ggagagctat gctagcatat cattcaggat gggctgggtc 13921 atgttttaat aacaagtaag tttgaacttt ataggttga aacaaaaaag atgtgtttct 13981 tgctcacagt tcatattttt tggagattgg ctggagcttc attccaggat actgccacca 14041 tctggaatgt tgacagttac cgtaacagag aaagagttgt ggaggctgtc acactggcaa 14101 ttaaattcgc tgacctggaa ctgacacatg ccacctccac ttatatttta ttggccaagg 14161 cttgttacac agccacatct aacttcagag aggtcaagat gagcaaatcc taccacgagc 14221 tatagatgga tgagtagcac tcattattat cacaattatt ttatttgtta taaaaactccaagaaggaga ggtactctat gtgaggaata ggcataggaa aatcagaggg aagttcttaa 14341 agatgagcta gatttcacta gatggcattg aagaacatt ccaagtaaat gaacagcata 14401 agcaatgca tgagaactt attgtcatgaggac tagtcc 14461 aggaaaagg tagactgga gaggaaggca ggaaccagaa caggacagac tgtgttcact 14521 gtcaggcagt taagtcttac tgtaggagcct tttaggag gcaagcagagct 14581 atgtgacacagg tagactga acaggagaat 14641 aggctcctcc atattggg gatccaaacc aaagcactgg cagagaaata gaaaggaagg 14701 gaatatttc caaatattc aaaacagaaa ccagagaac ttgatgacag aagatgaacc 14761 caggttcta actgattacaggactgact aggtac 14821 agttgagagg ttattttaa tcatgtttaa tttgatcact tgtggaacat 14881 caaccagaga tgtccatcag ttacaccaat tgtaggtt tgagagaggc ctgaggtaga 14941 ggcagagaag tggcattagtcag gcagattagtcag tgaagatgag 15001 atttcccagg gagggagtt gacaggaag gtagacaaag gctgagtgca gtggctcata 15061 cctgtaatcc cagcacttg ggaggctgca gtggg Petition 870260061675, dated 06 / 23 / 2026, p. 101 / 935 94 / 362 tagat cacaacaag atcaggagtt 15121 caaccagc ctggccaaca tggtgaaacc ccgtcttac taaaaaaaca caaaattag 15181 ccggggcgtgg tggcacac ttgtaatccc aggat2ggcagga ggcagga ttgaacccgg gaggcagagg ttgcagtgag ccagatcgt gccattgcac tccagcctgg 15301 gcgacagagc gagactccgt ccccaccgac ccctaaaa agaaagtaga aagatgtg 15361 tcctagagagtaga gaggagtaa caggcactaat gatcgagggg 15421 agagtcagtg aggtgaaacc ttagaggata gaccttcacc aaggaagtaa cagtcacag 15481 gcctaaatgc cacagagatg tcaatgaga vakactggaa atggttctt gatattaca 15541 gccagaactt catcaggatgagac gggaagggag 15601 gtccctgaag gagctagga gggactggga gatcatgacc cagagataag tgttgcaggt 15661 ataaaggga aagactga tcaggaata gccacaggat ccctaggcc aggcttcggg 15721 tggggtgtgttgtgtgtg tgttgtg tgtgtgtgtg tataaaatgg gagaccttg 15781 agtataattc tgtaactaaga agatagagca gtagagagga aaaggctgaa agamgatggg 15841 agggtaata gtgaattaga aaggtctgtg caagatgag aaaggatgag tctgaccattg0agca16021 gggcattcca tgatagcctc acctttctct gtgaaatgag agagtttagt ttacaagata 16081 tttctgagca cttcataagc caggttcata gactgaaaga agtggaggtg gagtgtgata 16141 ggtccttaag aataggggaa gtttggaata tctgacaagg gacagagagg aaaaaactag 16201 aaaaggcttt gcagaatgtg ggcccacaga tcagaggcta aggggtcccc atttgtgcag 16261 gagagtaagg gcagggaggc aaggctcaca gcccaaaata tagagcccct caccaaatga 16321 ctgcaggagg gcagctttcc tatgagagca tccctatcac tgttttcact ccgagtcatt 16381 aacttacgac ttactcagct ctgtttcgta atagcagact cgagtaatga gggtatgaca gcctctctct gcatgccaag gtatgcagcg tggatttcct ttttcgcttt ctctctcctg 16501 tggcttaggt gccttctgtt ctgctaccag gatagagaac ccagtgacta gtttcttcta 16561 gctctctttt tctgactagg tatcttgtca gaaatttctg cttaccagac ttcatggaga 16621 gggaatcaag ctttgaatca gggttgaaaa agtagagctt aatatatata ttacaaaatg 16681 ccactcacgt tcttgaggtt accttgtatc Petition 870260061675, dated 06 / 23 / 2026, p. 102 / 935 95 / 362 tataccacaa ctagcattct tttagaaagc 16741 accattaccg aagtaatccc tttcctggga attcaccca aaggttatt cccacttatc 16801 cccatctcc aaaataaaa agaaaatgt gtgtca6cttgagt ggagattag aggagtag gctgtaatac tgaaccaata gagacgaac taacagattg caggcatcc gttggcaaa 16921 aaacttatgc agttatctaa atgatagtta tgagacaat atgtataaca cattatattc 16981 tgagtgaaaa gaacagaagg tcattagttcaagga4 act tagtgagatg aacaaagatt tcaaggaac aaaataaag aaaaatttg ctttttatat 17101 tggtaggcgt atgggtgaa ttccaatttt aattttaatt tcatagttat aaattgttc 17161 ataaaaaag gtcgagcaccata acttagtggagtt 17221 gagaaaatt catctcctt caatcccctt tctctctta aaaaaaaca aaaaagagct 17281 ttgtcatgtt caggtgtgca acgaattctt tttccaatc tggaacttta catctgctat 17341 tgacaatcatccag tg ccaagtgtgt tggaataatt 17401 tttttaatg aggagatttg aaattccatt tcaattgcca acctgcctct ttcaacttct 17461 aaaaacaag taaaacaaa CAAAaacaca ctggtccta tcaccccctc ttgctact1 tatttactac 17401ccattgccct gattctttc caaacttctt tccaccagc ttgatttgt 17581 ttcagtcgg gtttattgag gcataattta cgtacagtaa attcatcct tcttagatt 17641 agaggtctat gcatttgac taatg7atactaga tggcatactaga tggcataa tagacacac ccatcactcc cgggttctcc ctgtcccttt tttgtccat ctcctctcct 17761 accccaacc ccttggcaac cactgatctg tttctgtcc ttatcattt gcttttcca 17821 ggatgttgta taggatt catcagccagcagcat 17881 agcacagtta tttaagatct atccgagtta ttgtgagtag cagcatcttt tttattgctg 17941 actagtattt catcacatgg atggccaca acttgtttat ctgttcacct gtcaatgatttata 18001 actaagttgt taggcaa ttgcaatttaagttatta t 18061 tgtgtggaca catgttttca attctcttag gtaaatactg agcaatggga tgctgggtt 18121 atatgttaag tctatgttca gtttctaag ttctgaaca attggatatc tatatgcaaa 18181 atacaaaat tacaaccattcattgaac tacaaccattgaac 18241 cacaggtgta aatgtaacc tagactaaaaacttcagg agagaaacat agcagaaaat 18301 atttgtgacc tgcattagg caagacttc ttagatttga cattgaaac atgatacata 18361aaaaatcttg ataaattgga gttcataaaa ataagaacta ctcttcaaaa gacactgata Petition 870260061675, dated 06 / 23 / 2026, page 103 / 935 96 / 362 18421 agagaatgaa atacaagcc acagacagag aaaatatttg tgaatttctt atctgataaa 18481 gggttgtat ccagcatgca taagacttt tcaaactca ataataaca atccaatag 18541 aaatgcacaa aagatacaag aacacacacaat 18601 caaaaaatt ctcaacatca ttagacactt gggaaatgca aattaaaaca acactaccact 18661 aaactacata tctattaaat ggctaccact ttaaaaacct gtcaagtgcc agccagaatg 18721 gatcaactacact taggcagt agggagt gccactttgg 18781 aaaacactcc gcagctctt atagttacac ataggactg ggggtagagg atggattgac 18841 tgtaagggg caaaacttcc tggtaggtt tttagaaggg tgaaattgtt 18901 tggtattcagtctctt tttgtcaaaa ctcacagaac 18961 tgtacactaa aaagtatat ttttatgctc tgctatttt actttaatct taaaaatagg 19021 aaggaaaaaa taaaatcaat gccactgctgc gacttgggc aagttactc gctta9ggtct81 atacattaag gataaaataa taccttcctc atactgttag 19141 aattaaatgt gctaatttat gttttatata tataaagtac ttggccggt gtggtgactc 19201 acacctgtaa tcccagcact gtgggaggcc gaggtgggca gatcacttgaggacaggagt 19261 tcagactag cctggtcaac atggtgaaac cctgtctcta ctaaaaatac aaaaattagc 19321 tgggcttggt gtgcgtgct tgtaatccca gctacttgag tggctgaggt ggga38gttca cctaaaatac gctgcagtgg gctccaccca ctgcctgggtlogagagcta 19441 gactccatct cgaagaaaaa ataagtactt gaaacatagc aaatgtttta taattattgg 19501 cttttttc ttattgttat tacttgcatt1attgagtattgtt1 gagagtattgtt gagagaaaag ggcaattagg ggtctgggat ggtttaagta tgaggagacc gagacacatt 19621 gactcagagt gagaaatca aagataagag aatgaagaa agggagta attctgaacg 19681 cacagacaa gttagttac taacgctgctgattagtactacta 19741 ttcactgtc atagctaat caatactt ctggagacca gaagtgactt gctggatcaa 19801 tgacaactcc tccacagatc aaaatgttca aatcctttt ctgtgttgta atcctaaatc 19861 taaagaacaca gagacaccacaca 19921 gtatttatt gatggtctg ctctcagctt caaccaagga aaagtcaaat tagtgttggt 19981 cagaaaacag aagggtgtta cgagagttct ggctggtcat tacagacttg gggatttttg 20041 attaaagaa gagaagaag Petition 870260061675, dated 06 / 23 / 2026, p. 104 / 935 97 / 362 aagaaacctg ataaagtgta aatatagcaa gcagggatta 20101 gtgtcctgct gggtcatgtt ctcacaacag tgagaatttc agagatttca taagaattaa 20161 actgctccac atgacaattt atttacctt ctggcttc caggagca 20221a atcaggca cttctttctg cctttgtttc aatttggtaa caaccctcaa ttttaggaca ggctaaacct 20281 agccacccta tcagagatga tgaagtagcc atctttttaa caggtgggga gatgaatgga 20341 atcagggttt gtttggttgt ttgtttaata actgctagta aaatagcatcaa 20401 ctgagtgtaa gggaggctcc agaaggcagg ttattgtagt atagatgtga ctcgacttat 20461 gatgatgtta cttcccgata aacccgtcat aagttgaaat atcgttaaat tgaaaatgct 20521 tttaatacac cgaatctacc gaacatcata gcttaggca aatcctactta 20581gca ggacgcacat tgcctacagc tgagccaaat cacctggcaa cacaggacac tgtagagtat 20641 cggttgctgg cccttgtgat gctgtgactg actgggagct gcgcttagtg cctctaccca 20701 gcattgagag tttcttatcg cttattagcaatc 20761 aagtgcggtt tctaccgaat gcttataact ttcagaccat catgatgttg aaaaatcgaa 20821 ccatcgtagg ttgggatcca tcctataaga cgagctacac tgccggaagt gtaagactgc 20881tatgctgccg gaagatgggg catagtggac aactgcaagt cctgacaaca ggaggtcagc 20941 atctgcgacc tttaacatcc acattgacac taccacagtc ttccaaacag agctgatgat 21001 atagtttgga tgtcgtccct gcccaaatct catgtcgaat cgtaatcccc agtgttggag 21061 gtggggcctg gtggggaggtg attggggtcat gggggcagag ttcttatgaa tggtttagca 21121 cggtcccccc ttggtactgt atagtgagtg agttctcatg cgatctggtt gtttaaaagt 21181 gtgtggcacc tcccctctct ctctttctcc tactctggcc atgtgaagtg ttggctcccg 21241 ctttgccttc caccatgatt gttaaattcc cagaggtctc cctagaagct aatgctgcca 21301 cgtacagcct ggagaactgt gagccaatta aacctcatct ctttttaaat tacccagtct caggccgggc gcggtgactg acacctgtaa tctcagcact ttgggaggct caggcagga 21421 gatgatttga ggtcaggagt tcgagaccag cctggccaac atggtgaaac cccatctcta 21481 ctgaaaatat aaaaattagc caggcatggt ggcgggtgcc tgtaatccca gctacttggg 21541 aggctgaggc aggagaatcg cttgaacctg ggagtcagag gttgcagaga gccaaaatgg 21601 agccactgta ctccagcctg ggcaatggag tgagaccctg tctcaaaaaa tatatata 21661 ttacccagac tcaggtattt ctttacctga gactatgaga gaatggactaatatagctga 21721 Petition 870260061675, dated 06 / 23 / 2026, page 105 / 935 98 / 362 agaattttat tttattttta aaaaaactttt acgtttgggg gtacctgtaa aagtctgtta 21781 cataggtaaa ctcctgtcat gaggatttgt tgtacagatt ctttcctgct cctccccctc 21841 ctcccaccct ccatcctcaa gaagatccca gtgtctgttg tttccttctt tgtgttcgta 21901 agttctcatc atgtagctcc cacgtataag tgagaacatg foottttgg ttttctgtcc 21961 ctgtgttagt ttgctaagga tgatagcctc caactccatc tatcttcctg caaaagacat 22021 gatctcattc atttttattg ctgcatagta ttccatggtg tatatgtacc acatttctt 22081 tatccagtct gtcattgatg ggcatttagg ttgattctgt Get ready 22141 tgctgcaacg aacattcgtg tgcttgtgtc tttatagtag aatgatttct attcttctgg 22201 tagtaatggg attgctgggt caaatggtcg ttctgcttt agctctttgc agaatcacca 22261 tactgctttc cacagtggtt gaactaattt acactcccac taacagtgta taagtgttcc 22321 cttttctctg caaccttgcc agcctctgtt atctttgac tttttaataa aaaccattct 22381 aattagtgtg atggtatttc attgttgttt tgatttgcat ttctctaatg atcagtgatg 22441 ttgagcttt tttcatgttc gttggctgca ggtacatctt ctttgaaaa gtgtctgctc 22501 atgtcctttg cccactttt aatggggttg ttttctctt gtaaatttaagttcctcata 22561 gatgctgggt attagacctt tgtcagatgt atagcttgca aatattttct cccattctgt 22621 aggttgtctg cttactcttt tgattgtttc ttttaccatg cagaagctcc taagtttaat 22681 tagatcccat ttgcaatttgtct tgctttgttct ttgtcatgaa 22741 atctttgcca ggtcctatgt ccagaatgat attgcctagg ttgtcttcta gggtttttat 22801 agttttgggt tttacattta aatctttaat ccatcttgag ttgatttttg tgtttggtgt 22861 aaggaagggg tccagtttca ataccatcagcagcattat tatc 22921 attgagtaag gagtatctcc tccgttgctt gttttccca ggtttgttga agatcagatg 22981 gttgtaggtg tgtggcctta ttttggggct ctctatcctg ttcatttggt ctatgtgcct 23041 gttttttgtc cagtaccattctctcttagctactaggtc tttcaaagtt 23101 gggtaacatg atgcctccag cttattcttt tttgcttaga attaccttgg ccatttgggc 23161 tctttttggt accatatgaa gtttaaaata gttttttttc tagttatgtg aagaatgtcg 23221 ttggtaattctgta accagattc tgagcatggg 23281 atgtttttcc atttgtttgt gtcttctctg atttcttcaa gcagtgtttt gtaactcata 23341 ttgtagagat tattcacctc cttgcttagc tgtattcctaggtattgtat tctttctgta 23401 gtaattgtga atgggattgc ttttctgatt tggccctcag cttggtattg ttggtgtata 23461 ggaatgctag tgattttttg tatcctgaga ctttgctgaa gttatttatc agctgaagga Petition 870260061675, dated 06 / 23 / 2026, page 106 / 935 99 / 362 23521 gcttttgggc tgagactagg gggtttttta gatatagaat catgttctct gcaaacagat 23581 ttagtttgac ttcctctctt cctacttgga tgccctttat ttctttctct tgcctgattt 23641 ccctggccag gacttccagt accatgttga ataggcgtgg tgagagaggg cattcttgtc 23701 ttgtgccagt tttcagggag aatgcttcca ccttttgccc attcagtacg atgtttgtgg 23761 tggtttgtca tatatggcta ttattatttt gaggtgtgtt cctttaatac ctagtttatt 23821 gacagttttt aacatgaagc agtgtttaat tttattaaaa gtcttttctg cctctgttga 23881 gatagtcatg tggcttttgt ctttagttct gtttatgtga tgaatcacat ttgttgattt 23941 ccttatgttg gaccaacctt gcatcccagg gatgaagcct acttgattgt ggtggtttag 24001 ctttttgata tactactgga ttcagtttgc aagtattttg ttgaggattt ttgcattgat 24061 gttcatcacg gatatcggcc tgaagtttct ttttttgttg tgtctctgtc aggttttggt 24121 atcagaatga tgctggcctc ctagaatgag ttggggagga gttcctcctc ctcaattttt 24181 ttggaatagg ttctgtagga atggtaccag ctcttcttta tacatctggt agagtttggc 24241 tgtgaagcca tcaggtcctg ggatttttta gttggtaggg tatttattac tgattcccta 24301 aatagaccga taatgatttt agaagtggag tcggtttttt cctggtccagtcttgggaag 24361 gtgtatgtat ccaggaattt atttagctct tctaggttt ctagtttgtg tgcatatggg 24421 tgttcatagt agtttctgat ggttgttttt atttccgtgg gatcagtggt aacattctct 24481 tcatcatttc ttttttttt ttttttttt ttttttgaga cggagtctcg ctctgtcgcc 24541 caggctggag tgcagtggcg cgatctcggc tcactgcaag ctccgctcc cgggttcacg 24601 ccattctcct gcctcagcct cccgagtagc tgggactaca ggcgcccgct accacgtccg 24661 gctaattttt tgtattttta gtagagacgg ggtttcaccg tgttagccag gatggtctcg 24721 atctcctgac ctcgtgatcc gcccgctcg gcctcccaaa gtgctgggat tacaggcgtg 24781 agccaccgcg cccggcccat ttctaattgt gtttatttga atcctctctc ttctcttctt 24841 tattaggcta gctagtggcc tatctatctt attaatttt tcaaaaaacc agctcctgga 24901 tttcttgatc ttttgaatgg ttttcatgt atcaatcctt cagttcagct ctgattttgg 24961 ttatttcttg tcttgtgcta gctttgggt tgacttgttc ttgcttctct aattctttca 25021 gttctgatgt tagtttgtta gtttgagatc taactttttg atgtggacat ttagtgctat 25081 aaatttaact cttaacactg ccttagctgt gtcccagaga gtctggtatg ttgtatcttt 25141 gttctcatta gtttgaaaaa acttcttgat ttctgtcttaatttaattat ttatccaaag 25201 tcattcagga acatgttgtt taatttccat gtaattgcat ggttttgagc gattttctta 25261 gtcttgactt ctatttttat tgtaccgtgg tctgagggtg tttgatatga Petition 870260061675, dated 06 / 23 / 2026, page 107 / 935 100 / 362 ctttggttct 25321 tttgcatttg ctgaggattg ttttatgtcc aattatgtgg ttgattttag agtatgtgcc 25381 atgtggtgat gagaagaatg tatattctgt tggttttggg tacagagttc tgtagaggtc 25441 tattagattcc atc atatctttgc taatttcctg 25501 cctccatgat ctaatactgt cagtaaagca ctgaagtctc ctactactat tgtgtgggag 25561 tctatgtctc tttataggtc tctaagaact tgctttatga atctgggtgc ttctgtgttg 2562 gatcatatgattattat1 tcttgttgaa ttgaaccctt taccattatg 25681 taacgccctt cttgtcttt ttttttcttt gttggtttga agtcttcttt gtctgaaatt 25741 aggattgcaa cccctgcttt tttctgtttt ctgtttgctt ggtagattt cctccacct8 gtccttacat attttatctt tatctatcca tccagccatc 25861 cagccatcca ttcatccgta tcatttttaa ccaataagga cttttaaaag cgcaaccaca 25921 acaccattaa cataaccaat aaaatctata acaatgataa aattcatct aatactcagt 2598 ccatcctctatc atcgtcttct tagaaatggt ctgttcaaat 26041 gagatcacat ggacagagga aggcgaacct cacactgtgg ggactgttgt ggggtggggg 26101 gaggggggag ggatagcatt gggagatatacctaatgcta gatgacaagt tagtgggtgc 26161 agcgcaccag catggcacat gtatatgtat gtaactaacc tgcacaatgt gcacatgtac 26221 cctaaactt aaagtataat aataaaaaat aaaaaataaaa aaataaaaaag tgaaaaaaga 26281 aaaaaaaaa aaaaagaaat ggtctgttca aatcacaaac cagattcaga aacaatagcc 26341 atacattaca tttattaat atgtctctta aatttcttt aatctattac agtctttgga 26401 atttttatgt cttcgtttat ccttccaatt atttaaaaa aagtatttt gtattcattg 26461 aatagacaat gcttgcagaa aagtaaaa aaaaaattt agtacaaaaa ggtacatagt 26521 gagctgttcc ttagtctccc ttcccagaag caatgttacc acttttgtac aaaatagtctc 26581 tgcctagaca cacatgccag tccctaaggt ggctgtaaca aggtggttaa gagtgagaac 26641 atgaattcaa attcctatta tgccactcac taagtataaa tcttggtcat ggtacatgcc 26701 tctgtgcctc agtttttaat aatggtacct acctcatagg gctgttgaga gaattaaatc 26761 agataagtgc ttaataact attaatattt acattccctt ttggcttttt 26821 tcccaaatag cagagtggtg cacatatgtc ttcatttat tggcttgttt tttcacctca 26881 catcacattt tgatgaataa ttccatacat gttgttatag atttgcttca ttctttgtaa 26941 tcattgacta atattccattgtatgaatat gctactgcta aacatgtacg ttatttccaa 27001 cctcttatta tcaagaaatg ctgcaatgaa tatccttgta Petition 870260061675, dated 06 / 23 / 2026, page 108 / 935 101 / 362 atactttagt ggattcatgt 27061 gcaaaaaatat tcataggata aaatcctgaa agttaaattg ctgagctaaa gggtatgtgc 27121 attttaatgc tttatagatt gcccagctgc ctcaaaggag gttataacaa tttacactcc 27181 caagaaaaaat gcacaagggt cccacatttcc ccataacccta gctaacacag gatattgcta 27241 aatgctttca tctttgtaaa catgatgtat tgaaaatggt atctcaagt tttaatgtgc 27301 attttctga ttgtgagaag ataaaggaaa tgtagtacaa ctaaacatca gcagtcaaat 27361 gacctggcca tgactcctga gtgaggacac tggtaaacac catcaggatc caaacacctc 27421 tgtatttacg aagaggatgc tccctatgg atagcactaa gcttatttca tgtatgtaca 27481 tatgtagtta gttaattaca tccagcggtg gcaaagggct tgttctgacc caatgaaact 27541 ttctctcctg gcccccttcc agcatgtggt caggagtaga gtgttgtggc catgaggcat 27601 gcatttgtac agatgactac ttactctcc ttgaaacatt tttttccatt tgcttccctg 27661 ctgtctcact catgggtctg ctcctaattc acaaatcact cttttcccag tcttcttggt 27721 tgggttttct cctcttctgt gcttgtagac atggggagac cccagggctt ctctcttgaa 27781 ctacagcttc tccctgggtt catctccttg ggatgtctgt tccaatgggt ttaatacta 27841 gggctaggac tagggagaggtcattgaggc acttagcaca taaagtttaa ggaaacattc 27901 tttatcaggc ccatgcaagt gcaggactgg ccctggaggg tgactaccac cttacctttt 27961 ccaccctagg caccttgttt gccttaccct agccccagtc ctctttaaca ccccact 28021c ctccagaaac ataaatccta tttgacattt ctacttggag gttttaaggt 28081 aactcaaacg taaaatatct aagacagaac tcttgcatca cttcccatcc tggggcccaa 28141 gcctgtctct tctactagtc tatctcagtt aacagcatttca ccatttaattc 280202aaaaaa ttgaagtaat ccttgactct tcttttttt ttttgagac ggattctcac 28261 tctgttgccc aggctggagt gcagtggtgg gaccttggct cactgcaacc tctgcctcct 28321 gggttcaagc aattctcctg cctcagctct ctgaccctcctcctc 28381 ccaaagtgct gggattacag gcgtgagcca ccgcacccgg cctggattct tttttttttt 28441 tttaaacaag tcctatcttc catctccaaa atgtatccca aatctgacaa cctctcccac 28501 cgtaggccag cccccatct t ctggacattt 28561 gttcttcccc acccccttgt gatcactatt cagcattcag aatgatcttt tatattatg 28621 aaggagactg tgttcctctc ctacttaaaa ttctctagtg gcttcctaat aaatttagaa 28681 taaaaagccaactcctcgcc atggtcacca ggccaggatc cagtgggtac aacaatctgt 28741 tccca Petition 870260061675, dated 06 / 23 / 2026, page 109 / 935 102 / 362 gcaca ataatcccac ttctgcctcc ccaccattca ccaggctcca ctgcactggc 28801 tcattcctgc ctcagttgtg cttcttttcc ctggaaagtt ctttctgtag atctttaaag 28861 ggtgatttcc ttctcaacat tcaggtgtca gctcgtttca ctttcctgac catgcccatc 28921 cactcagaga tcactcaaaa tcccattacc ctattttatt tctccatcat atgtatcact 28981 atctgaaact atcttgttgt tgatgcaggc tattttcttg accccttcat gggactccca 29041 acaggggtac cccatttact cagcctgccc tgctcaacct cttgcaggag ggagcacacg 29101 agtgaacgag tgcaggaacc agctggctgc tttagtgctg tgaggagtaa actccatgca 29161 ggccctgcag cagcaaccag gtaggggtgc ctgcaacccc agggccccag agggtgtgtt 29221 acaatgctct cgtagctctg ccatctgtgg acagcagtgt gttgtcagct cagtgggccc 29281 tttgcttcat catgtagggt ggctgccctc tgcctgtgag ggcaaagggc cagggtgaca 29341 gtctttttgg gtacccacaa tttgtgcatc ctgaattctt gtttggtgcc caagaagaat 29401 ggggtcacac agatgaactg aaggatggtg aatgcagaga attagcaatg aaagtggctc 29461 tcagcagaga gagaagctga aaagggaatg ggaagggcag gtcactctcc cctgaagtca 29521 agtcacatct ctccaatgtc cagccaccat ctctgaagtc aagtttcctctctctgatgt 29581 ccagccactt ctcctctcta ctggctgagt ctggggtatt tataggcaga ggataggtgg 29641 tggggcaggc catacataat tttggaaaag gcaacattct attggtaaaa agacattatt 29701 cataaagaac caattcggaa agacactcggggg ctttgggctg 29761 caggtttcag gcttttcagc tcaaaagtga ggtttttcca gggacctgcc ccgtctgcct 29821 aaaatttcta cacttctgtc attgataccg ctggataaca gctctcctat aaagttcagg 298aatacttaac aggtaacttac ggacagttct tgatagggtc tctcctaact 29941 gttgcagtta catagcaact gggttggagt catctttctct gggcttgaca tccaggacag 30001 cttcttccct tgtgtgtctg gtgcctcagt gctcctccag gcagccttc tctccag3 aactcaagct tccaaaagaa aaaaaagcag agactgctgg 30121 ttctcttatc aaacaggcct ggaactggca caatgtactt ctgctgccat attcaggagg 30181 tcaaagcaat cgaaggccaa tccaagttca aaggcattggagaagaatga3404 agtgacacat gcgtaaaagg gggaaaagca ttgattgtgg ccatttttgg 30301 agataagcta tcacgtttat ttgtttgttt gctttctaat ggtctgtctt ctcccattag 30361 gttataagct ctgtgagaca acaggaatct tgtccatcttgttttatggc tctacttcca 30421 acacctagaa taatgcctgg Petition 870260061675, dated 06 / 23 / 2026, p. 110 / 935 103 / 362 cacatagtag gtgctcagtg aataacttaa gcacttgata 30481 catgtttggg gaactaaaat gaacagaatt aaacttcccc agattggtcc tgccagattt 30541 gctgatgcca agcatgctga tgcctcacca gatgaaagaa gccctaaaaat gtagggtttc 30601 gctttctctg caaacaagaa aaacttgccc tgaacacaaa atctagaaat agatttggcg 30661 tgttttctac attgaaatat ttcccgtagt accagaaatt attttcccac agctttgtgc 30721 tacattaaaa tattgaagtt gactgaaaaat atctccattc tttaatcttg gtgtagacta 30781 gaaacaattt ttttgtaaca aagtaaaatat gaaacttcc taatatttga actccccaga 30841 tatccccaga tatctccaaa cttaaaaatat cattgcaagt taagataaat ttttttaaat 30901 gactaccgag aaaggtcatt aaaggcttgg ttattaaaat gtacagattt gggttataaa 30961 gccagaactt atttgtttaa atcattacat atgaccaagc acagaaaata aattacctca 31021 aatctcctct ttgctaattt ttactggtaa actctataaa atgatcctat ctttaaaacct 31081 ttttgtaaac cccttataag ttagtaagtg agaatgtatt catcagaagg attttagtga 31141 tgtttgaaat taaaaaagag agatttgatt tttaaaatta tacttgcaga ctactgctaa 31201 tgaaacttct tctaacccta gttttgtctt atcttcagtt tttccaagatt tgctcaaagc 31261aatcccagtg agcatccacg tcaatgtcat tctctctct gccatcctta ttgtgttaac 31321 catgtgggg acagccttct tcatgtacaa tgcttgga aaaccttg aaactctgca 31381 tggtccta tt gttcaagctgtacc ttctacctct 31441 gagacacaat gtgctttca atatgtcaa aagaccgtct acctaaatat aaagttataa 31501 tcttacata tatacatgga tgcacactgt agtatatac ataatacaa aaagtgtgga 31561 ataccacac ttgtatatcaatcaaca caataagtgga tatacgac 31621 taactgtgat gctgacatta aattatattt ttgaagatgt atcaagagg aaacgctt 31681 gtctcaaaa gttacatggg aaaagcagta tgtaaaacatt gtgaacctaa 31741 tttgattata gctgacaat1tatata8atagggaata gggctatata tatatatata tgaaagagat agatagatag atagatagat agatagatag 31861 acagacagac agacaataca gactccaatc tgttggtcgt ggttgtctct gacccatgac 31921 gctggggg acttttatt ttgctcatac ttcatagtt8ttcaatt tcattagt tcttagatt atacatata ataaaaataa ataaatggca tcaaaaaga gtaaagggcc 32041 agtgttccgc ccacatatga gcagccatat tcaagcctgt agacactttgtgtagcctaa 32101 tgctaggtgt atctgggcaa ggataaactc taaagccaga aattagttca tcaataaaca Petition 870260061675, dated 06 / 23 / 2026, page 111 / 935 104 / 362 32161 tgtgctactc aatagctagg gctgatggaa aagaatataa aacccagtct gtgccaaatg 32221 gtgcttacta tctgcaagtg ggagaaggag aaagacgaga aaatgaaaaa tgtgtgtata 32281 atttatatgt agctgttctg taggagatct ctgacttcac cccattctaa ctttgcaaaa 32341 agatccaaca ctttgtcaga ttcctggag gcaagtaatt ttattgatgg tttcatggag 32401 ggatacagaa cgataacaac tcacacaaag caaacaatgt aatgaaaatc tctattcgac 32461 tgtttcttt tctcctgaag ttgccctttg gctgccagct accaggcacc aggctcaagg 32521 tactttcttg ctcttgacac tactcccttc tctcatacaa ttcaacccca accacaaacg 32581 tgtatagatc tctctctcta taaaacaaag gcctgtagtt aacaggaggt cacttgcagt 32641 gtagcctctg ttcattgtta cttgtgcaca ctgcttaggg tctcacccca tccacattct 32701 gctaatcaca ttatcacc atccaatgta gatctctcca gtggagattc tgctatatt 32761 ttctttagat ttgtcacaag tatataatac agttttaaat tgtacagatg attatcctat 32821 aacagaagag tctaagcctt ttacatcttt gtatctctaa cgaaagcatt cagcatgaag 32881 ctctgtacac agcagacaat tcaatatgaa tttgctgact tgaaacagca agcctagaaa 32941 ggagatgtta acttggtcac ttagacagaa caggtttcag caatcagaattcagatgaca 33001 tggaactggt agaacaggcg ctttgaagca ataggacatg agccagtgag gagagggatg 33061 gaatcata aacaaaggcc aagggctttg caatcagagc tgaagagcca agagcacagg 33121 ctcagggtgt gggcagactg aatgagaaag tgattcaatc acatgtgaaa gtccagatga 33181 gaagagagag ttgggattac ttctgctcac caaacatcca aaaccaaaca ggtggatccg 33241 ggtggtgtgc tgttttactg atgaccatta cacagaattt taacagaagg aatgtaagc 33301 agtggttctc aaactggagt tcccagatga gcagcgtctg catcatctgg aaacctgata 33361 aagcagcaaa ttctcaggcc ctaccccaga cccactgaat cagaaacttg ggggtctggg 33421 ggagatggc catctgtatt ttaacaatct cccttcagga gattctgagg ctggctcaag 33481 tttgaactac aggtagttgg ttcaacaggt gttggtggac tgacaaaca aaagagactc 33541 cgaggtaact ccaagatggt aatgtcagaa agcagctacc acccctaggg cttggggga 33601 ccaacaaaag agtttggcat tgccagaacc tagaatcttg aggagaggcc ccagagcatt 33661 gtgtctcaga ccttgaggac ttggcactgg gacaccatga ggggtttctg ggtgtgggaa 33721 agggctgga actccccagt tgctgccacc aggagaact acaagtgaag tggaaggtgt 33781 gggccttct cccttttctt ttctcgtctt ctctctcccc Petition 870260061675, dated 06 / 23 / 2026, p. 112 / 935 105 / 362 ctggtgctca tgtttgacag 33841 aaaacagctg aaaaggcaga actagttgg ggagtcttga cctggcatca taaagcagag 33901 aaaagcaag ctggagtgaa ggtgagacac ag3acc9gctcat cgctccagct tctgaatgaa attctgaaga acagcgcact tggagacaa attatttgac 34021 agttctgaca gacgaccaa ctaacagcat ttgaaagca agatgactca gagaatacag 34081 atttaatcc aaatcccaga tcctatct31caaggaccta4aggcctt ctgagcacac aaatatatgc aggaatgatc aggacctgtg cctgcattct attctgtctc 34201 acccaccttc aaatttgttg taaaaacatg ggctcataa aggttgtga atcagggact agggagtag 34261 gagagaagg ggaggaggaact atcaggtacca tgcagaggat 34321 aaggccagt gttttagat cacccagtgt tttctaagc cccaatact tatttgaa 34381 tatcaaatg ttcaatact aaaaaaaaa ccgttacaac aaaaacat gttgaggct41 cacgagt41 caccagtgt gataaacagg tcacttgga atcacagact 34501 tcctcattcc ccttaaatct catatgtac ccagaagccc tggaacttt ggaaggtgtt 34561 tattcacagt tgtaatgtcc atgcagaccc tggctctaag acccaatcaattgcct gtta6ccgcct gtta4ccgctacattctaag tgtgagccaa tgcgtcacac actcagaggc 34681 cagagactgt attgggtcc tttatttcac gtacgagtca cattccatta agacccca 34741 gaagtcagct ctcttccact gactggttct cttcccttgt ttctcttgcc aatgtgtgct 34801 gcccaggtgg cagtgctcac tgtcagcaga gaagaaaaat gctttcctcc ttggacctct 34861 tttctcttt tctcctccct actcacattc aggttcccta agcttccccg ctccttgtgc 34921 tgaagtcatt ctatggtcat ttcttcaact gtctacttcc ctgctggatg ggcacccaag 34981 acttggcatc ctggggcatg tagaagggg aaagggaagg gaagggaaaa gaagtcctcc 35041 caattgtcta tctggacctt tccacactgc ccagagtact gctatgggca tctccttatg 35101 tctcccgatg tggtgcatgc cagaccctgc aggtagaaaa ggaagaaag caacccattg 35161 gaccaggcca gcaaaggctt cagtcacaca gctggctcat acttatggct tcatattctg 35221 ttgcctcttg aaccagacat ttcttccact ctcataacct ccagtttagc tcgtattcct 35281 cagcattctc catgtaatat tgttgcatga aacccatgca agtcagccaa tttgctcttt 35341 ctcatcttgt catttaataa ttgatgctga gaagtctttt tcccaaggtt tttagtaata 35401 ccttcatcat ccccatagt tcatttggg cagtgattcg cttctttgac tgtacattag 35461 aatcatctgaagaactttct aaaactactg atctcaggtc tcaca Petition 870260061675, dated 06 / 23 / 2026, p. 113 / 935 106 / 362 caaca ctaattaaat 35521 tatagtctct ggtggggtag ggcttgggca ctgctatttt accttaagct ctctggagtc 35581 attctaattt gtagccagtg ctaagggttg caatataagt gaatatattt cacgtatttg 35641 tcaaacattg actgagtgcc cattatgtgc cagccattat aataggcact ggtgatccca 35701 cagtgaatca ggcacacaat gctgtcttca cggagcttgt tgtctagtgg gagagtcaaa 35761 caaaagtgta tatcaataat taagtgatta cagattgcaa taattacaat aagggtgata 35821 aacaggttgc tataatatac aatagtattg cctttcacca gacatttctt aaagaggtaa 35881 atcatctatc agacaccttt taaaaatctc atctaatttc aaaagtgtac ataaataatt 35941 aagtgattac agtttgcaat aattacaatg agggtgataa acaagttgct atgaaagaga 36001 aagatagcag agatctggct ttgagatggt ggtcagggaa gactgctcca atagctgagt 36061 tctaaagcta agaaggaact gagaaccttc acagaacgtc ccaagtagaa gagaaagcac 36121 actgaagact ctagggaaag aggtctgctt gttgtaggaa ccgaaagaag gccaatgtgg 36181 ctaggtgctg ggtagtgagg ggaaatggca caaggaaaaa atgaggttag agagatcagt 36241 tgataccagt taatgttgga ccctaaacat taaccatggt aagtctttta gaattgattc 36301 taattgcaat gaaaaccttt tgaaagattttaaaagata tctgatagct gatttacctc 36361 tctaagaat gtctggtgaa agacaatacc atcacattgg agatggaaa agatgaatgg 36421 attctaaaa cattctgaaa gtacattcaatca aatgttttc aggtagctt1 aattagt4 tgcacta gtaagacaag ggaggagcag gcttgcagtt taggcaga 36541 aagggtggg gagaagagct cagcactaaa atcatgtgtt ccattgggg cacatcgagt 36601 ctgagttgct atgagaccac caagtggaga tgccagctt3 acgga6gttgattaa gaagaggtct agagaaaga tgtatattg ggcattattc ggatatagat 36721 atttagtaaa gcataaaat tggatgagat cacctaggga gagaatgcac atagataaa 36781 actgacctag gaccacttca tgtctaaaac accaacaaatcaagca ag6atca4 atcagt gatctaatta aactaagag cttctgcaca gcaaaagaat cagagtgaac 36901 aggcaaccca caaaatggaa gaaatttc acaacctact catctgacaa agggctaata 36961 tccagaatct acagtgaact caacaaatt tacacaagaaaacc 37accacaaaacc aggacatgaa cagacacttc tcaaagaag acatttatgc agccaaaaa 37081 cacatgaaaa aatgctcacc atcactggcc atcagagaaa tgcaatcaa aaccacaatg 37141 agataccacatc Petition 870260061675, dated 06 / 23 / 2026, p. 114 / 935 107 / 362 tcacaccagt tcaaatggca atcattaaaa agtcaggaaa caacaggtgc 37201 tggagaggat ctggagaaat aggaacactt ttacactgtt ggtgggacta taaactagtt 37261 caaccattgg ggaagtcatt gtggcgatt ctcaatggc tagaccagatc attc 37321 gacccagcca tcccattact gggtatatac ccaaaggact ataaatcatg ctgctataaa 37381 gacacatgca catgtatgtt tattgcggca ctattcacaa tagcaaagac ttggaaccaa 37441 cctaaatgtc caacaatgat agacttt aagaaaa 37501 tactatgcag ccataaaaaa tgatgagttc atgtcctttg tagggacatg gatgaagctg 37561 gaaaccatca tcctcagcaa actatcgcaa ggacaaaaaa ccaaacaccg catgttctca 37621 cccatggtg ggatgac ggaaggggaa catcacacac 37681 tggggactgt tgtggggtgg gaagaggggg gagggatagc attaggagat atacctaatg 37741 ctaaatgacg agttattggg tgcagcacac cagcatggca catgtataca tatgtaccta 37801 acctgcacat tgacctactactactag aataataata aaataaaata 37861 aaataaaaaa acaaaaattg atgtaggacc aattcctgaa gaacactgac agttaattttt 37921 ttggtttagg aggaggagaa gccagcaaac gacactgagt agcaatatcc aaagaaaaag37981 aggaaaaagg aaaactggga gatttagagt gtcccagagg gatgtttca agattaccat 38041 cagcagtgag ctttgtgtaa aggtggcctc ctgtaataga ggtgcgggca ggagaaggca 38101 aaagcttggtgga atatacagt ggaagagaga 38161 gagagagaga gagaagaga aagagaga gagaacttaa ggaggtagag gagagagag 38221 aaccaaaaaa gagggagctg agtatagag cattagtt catagttttt agttgcggca 38281 ttta gttatagttgccattg gtgtttccca gttgatggga 38341 gagggtctta cctagatctg catgtaaag ggagtaggcc agctggcaga cttgacatgg 38401 atcagtgta gaacatccta gcagttgt gatactctc tgagaatgac atgaaggagttagtta 38341 ttgaaggattcc 38401 ccaccaaaat gtggacttat tgcaattgt 38521 atttgttacc atttgcaatg attataatta ttctcttata ataggctt cttacatata 38581 gctctctta cacatagcgt catgagtta gccttctt acatatagtg tctgcagccaatga1 gttagcagccaatga 38521 gccttcttt aaaaagagga cgctcctagt 38701 atgggcctaa ttaattatga taattacagc tatggcatgg aacataagca cattcatata 38761 cacaaagaca ataaaataa gaacagtt Petition 870260061675, dated 06 / 23 / 2026, p. 115 / 935 108 / 362 ca aaaacagaac agttacatta tatatcagtt 38821 tcagtatgaa tataccctg gactctgaaa tatgtctggg gcacattatt ctgtaattgg 38881 tggtgaaaaa aaatctgcat cttatctcta cgccaatcct ct tatgattg 388941ca ggagttcgag aaagagacac agggatgtcc agtcatcaaa gccgcagagc ctgaggaaga 39001 ataaaggatt tgtggcagga aaacccagta atgaatgtat tctgctagtt tctcagcata 39061 gaacttagaa aagaggccac agaagggaaaa 39121 aatgggcaaa gaatttcatt ctcatatgca gggcagtggc taaaggggca gtgttgtgag 39181 gaatcacatt ccaggtcatt catgtccagg gtgtggtagg aggactgtgt ttcatttatt 39241 ttgtacatgg cccagctatg accgattgtcacattgc 39301 tgcaaagaga ttcttatcct actcagaatg tacgtcttct cttctgtttc atttacagtc 39361 acaacccaag tccttgcttt gacctccaaa gcaccacttg atgtatccac ttcagaaaca 39421 cacacagaca gctcaccctctctccctcctcctc tcaaaccacc 39481 tacttccttt gcattcactc ttccttcagc ctgaaataat cttcctccaa atatctacct 39541 tctcactccc tcacttctct caagatacac ttaaatgtta tattccctat gaggcctccc 39601 ctggccatccctccccagcc ttcctaccc ccctctgc tttattt tctccttaat 39661 atatatcaca ctctgataa ccattgaatg tacttatcaa gttattgcct ctctctccct 39721 ttccattgtc tccatcactg agagctctgt gattagaga8accattagt gtgctgtacc cccagttccc acaacagcgc aacaggcact cataaatag ttgttgaata 39841 agtgataaa acagaagtag ctgcatattt tctgtaaca atgatattc ttctgaaaat 39901 gtcatatttt cagacatattatt aaa tccaa6atattac aa tccgaaatata gaccatttct tctttgcatt aatcatcctt ctcaataata taacatttgt aaaacttagg 40021 ttagatatgg gcttcac ttcattac agaagataa gtgaaaaggc tagaccat 40081 gtgttattc cttcatctac tgactaccatcct 40141 acaatctcaa aatctacct ttgttattaa ctcactcac ttgtccctct gtccctttt 40201 agatggtagc catcggtctc tggagtg tagagtcaga acaacttcta tttgggact agggag 40261 aattcattcattctctacttaa tgggattgc tacataattt 40321 tagagaaaat taacacctac acttgtaaag ttgtggcttt cccacaccta tttacatct 40381 ctcaatattc cttgaaaagg aaattatcaa ttatcattc tatattggca atgaatgcc 40441cctaatatct gtcacctata agacaattga agatgatgtg ttgaaagctt tctgaaaatg 40501 ctgatcat Petition 870260061675, dated 06 / 23 / 2026, page 116 / 935 109 / 362 ta ctttaaatgg aattgaaatt ccagtttatt atttccaaaa atatgatctt 40561 actgatcata ggatacatt tcatacatt tcagagattt cttcccttc gaggagccaa 40621 accatagga cctctggact cccacacaggcgattac 40681 agtgccctc aggatcattc agggatgaag aagcaccct cattggccat gtcctacgtt 40741 cccatatag taaggactgg aggaccag tgctcattc tgcagtctca ngagctg cagtcatc 40801 agattagagcagt aggagtg catgaat attgactgat 40861 cattcatggt gtgacagccc tataactcag ctatcctatt cagtcagaaa tttaactcagt 40921 aatcaaagtc attaaaagga agaaaaaaa aacctacagt accagacaga tggtgggaat tgggactgaat tgaga81 ggtcattgag taagacactg ggcagcaaaa 41041 cctggcctt gtgcctggtt atactccaca ttatacccc agcaaggttt ggcaggattt 41101 ccacagtctt ggcttattct aacctttctt gggagcagga gcagcat6gattgg t41041 ggaatctgtc caactggcac cgtgtgaatt tgggcttg gtgtacatgg 41221 ataactggga aaagaggag agagacatgt aggactgatc ctaccgttg tgaagtcttg 41281 ggcactagta tgaatgagaccacca tggcctggcacacagta 41341 aagagcctca agcataggtg tgtggacatt gcaccatgta tccaagctct gaccatgcct 41401 cttgaaacag ctattcctca gccaccctt gaccatggga gga ggaatgaccc aggagaatg 41cagagag61 cttagacct accaca agtcaatcc ggggtcccag 41521 gagtattcc ggggtggac taaatgtga gtcaggcatg ccagatgggt atgttctatt gacttcagg 41581 attcctcatg ctgtgggaag gaacctctc agagagaga cagagcagaa ggt1cggagcactaaat ccctcttgct ggattcaag ggtcatactg gaagagtgta 41701 ggttgagtct tattctcaca tcactcat cacttacaca cttcttat agccttagca 41761 gccatgccac aaagagaaac tcttcatgca tatctttgt1atttacttcg attactaggt ccatgtcttt tttagagcca tggacagaga gaagcaaaaa tataccaagt 41881 tcacactgag ttgtctccct tcatactct tagcagtcac tgaaggtta tgagactcag 41941 gctgggtttc tatcctctt accaccgactgattacga accaccgatagattacg 42001 tccagagcaa gatctcagac tgtcctctct actaccagac accacactt gttttgggg 42061 ctgtgtgctt gaatattag ctatggcaa aggcttgag tcttgaca cccaagtaa 42121 cttttactt aggataccattg tg tgctgtctcctt Petition 870260061675, dated 06 / 23 / 2026, page 117 / 935 110 / 362 aacaaagcag 42181 tacctttgaa atatttaaca acttgaaaag gaaaccgagc ttgaattttc ctttcaggtg 42241 ctcaggaaat aatgtttcac ttctgtctga aattcaccat ctcctcagac aaagaaggct 4030ctta2atggatcga attttctcca caattttcga ataaaagata aagagaaaac 42361 agcactgcag cctttttgtt agatctaac aataaagaaa tatacggtt ttgccagggg 42421 agagctctgg ttttaagctc agaatacaaa aataggctga caaaatttta caaaggaata 4248ctcactgacta ttcactgata gatggtagaa agtgaaattt caagaaaatt atattattg 42541 attatttgat gatgattaag ctgattggcc agtcctatgt gaaattctaa agtagaagaa 42601 atgtgatgtt gtcttttctg ctcacctc ccctcattcc tacccccaaa tctctctc24gc61 taccaaaa ccagcctgac ctttgggaaa ggaatggggg ctgtcacttg caccgtagct 42721 cctcctgcct gcagtactct ccccccacag tccagcctcc ctctgctcag ctaacttttc 42781 ctatagctcc ttctggctac tttaaggaa cctctctcctcgcgctac 42841 acagcccctc tactatccct tgattacatg cactgtaatt ggttagtaat tgattttatg 42901 tcctctgcca aattatactc catgagagca aaaatcatga gtattatctt taatgtttaa 42961 atctccacaa ctatcccca tataagtctagagaataaat gatgagtga attaatgaat 43021 agaaactcaa gccattatgt tgccactcct aggatatttg gattacttt aactgaagag 43081 taaaaagcat tacctgtcc taaaggagac aaattag tggagagta tt4tagacagaca4a tcttttgtgt tgcctaccct gatgtagtca ggtgtccctg 43201 atatggggtg ggctgaggat ttgaaataaa atacctatt tgacattgta agtggaggaa 43261 tcaggattg aaaccaactt ggtttgacct2aacaatcaat4atcaagct gaaaaaagga atccataaaa accatatgaa tagctaccaa ttagtaagca tttatagtg 43381 tcaattacaa agccaaatgc aaatcatgct ttatttat tagccacctt ttatagatga 43441 agaaattgag acctgaatat taaaatttacaggtagcc taaaattagtagcc ta gtttgaaccc aaattggttt cacctaggt agaaaaccat cccagcaagt ctcctattaa 43561 ctggaacct attgtggtgg cctgagatat aacagtagct gtggaagcgc tgtagagtcctcc 43621 tggccatccct atgcctgccactcct ctgcttgc tccctgtgcc 43681 atccaccat ctggaagtct cccagtgtcc atcttcgggg gagacactca ccagagttc 43741 cagcttccag ccagtagga gtgccgctgt cccacagcaa tctcaccgaa1agg38atcagcccaatgagtg atagatgagg gggaaaaata Petition 870260061675, dated 06 / 23 / 2026, p. 118 / 935 111 / 362 ataatagtgt 43861 actaaacaa acaaatgttt atttctca cacataaaaa tctgaggtt gaagtccagg 43921 gctggtccag aggctccaag gatctgggat ttagactccc tctttctgt tttccag ggcattctt438cttgct1 gtccaaaatg tatgctgggg ctccagccat 44041 tgcatccata tttcagccac aggaaggagg aagtggggaa gaaaggacag gccctaata 44101 cctgtatagt tcaagacag tatcccgccc atactccca accacataccta1tcgact4gttgaaccta tcacatgtct agccaaaaat ctgaattctg ttacaaacaa 44221 ggagaataga gatgtgcgcc acctcaatac ctcatccata gctacctttt ccttgtgca 44281 gctgtggcca agtgaagct gaaggaagct4 gaaggagctg4tggtaggacc4 ggctgcatga tgacattta tcctgcatgg cctgtgaagt acagagaaat 44401 attttctt gaagccacat catagcagtg gctgcttgt agcctgattc caccattatg 44461 ccttaagct gcctagcaat caggatg tcagcctt 44521 ttgtagatc agcttaattc taaccaccctc cttacctccc actgcactcc tacacgcaca 44581 cacaatctt cttcactcag agcagaacca taacccaagc cctaccacct agagactgaa 44641 gatcaggct catgatcaca aatgcacaaatttttgt gtggataatg tcaatgggga 44701 tgatggtaag agaattcctt ggtttacaca ttgaccctct tccctgtccc ttacaatcag 44761 gaaatatttg tcccaacacc ttgtttcttc tgttgcaggc tcctgtggct gtcttgtcat 44821 gatatgttt gcctctgaag tgaaaatcca tcacctca gaaaaaattg caaattataa 44881 agaagggact tatgtctaca aaacgcaaag tgaaaaatat accacctcat tctgggtcat 44941 tttcttttgc ttttttgttc attttctgaa tgggctccta atacgacttg ctggatttca 45001 gttccctttt gcaaaatcta aagacgcaga aacaactaat gtagctgcag atctaatgta 45061 ctgaaaggca aacctttcta taattttaca agggagtaga cttgctttgg tcacttttag 45121 atgtggttaa tttgcatat ccttttagtc tgcatatatt aaagcatcag gacccttcgt 45181 gacaatgttt acaaattacg tactaaggat acaggctgga aagtaaggga agcagaagga 45241 aggctttgaa aagttgttt atctggtggg aaattgcttg acccaggtag tcaaaggcag 45301 ttgactagaa tcgacaaatt gttactccat atatatatat gtgtgtgtgtgtgtgt 45361 gtgtgtgtaa gatgtcttcc tatcaaaaag atatcaaagg cacatggaat atattttaat 45421 aaaaaacaaat aatatctcta atatatccac acatttgtt ccagatttca gaaaactgag 45481 ctgcaatcgc tttcctaaaacagtagtgta ttaaa Petition 870260061675, dated 06 / 23 / 2026, page 119 / 935 112 / 362 tgaac atctataaaa tgtatcaaca 45541 cacattttaa aaaatttgtt taaagtatac tcttaggcca ggcgtggtga ctcacacctg 45601 taattccagc acttcaggag gccaaggtgg gagatcatt tgagttcagg agttcgagtt 45661 acagcctggg caataaagtg agaccctgtc actaacaaaa ttaaaaaata aataatat 45721 aaaatatagg ctttaaaaaa gcatagtctt attaaccatg tctgttggtc aaaatctgca 45781 aactctaaaa gaagaaaaga agaaaaaacc aagcttaggg tattttcct cccgtgcct 45841 agtcccaatt acattcacga cagattacttc aatgaacata attgttagga ccactgagga 45901 atcatgaaaa atgatctctg cttagtacat ttgatgcaaa atgacttatt aggggctgtt 45961 tttctagcta tagtgtctcg agtactaata tgcaattatg aaaattatat taaatctggg 46021 attatgacgg tatcactgta tcatcttggt cttgttctgg ctgtcaccaa gcatgaccca 46081 ggtcaacttt tttttcccc tgaattaccc atcaaattga tctgcagctg actaaagcc 46141 acagctgagc ctggaactga cccttccttc atcctcaacc tgctgtcctc cagaaagcac 46201 caaggaaaaa gcagagaatg acagcaaaca gatcactagg cctctgacca caggtgctga 46261 gtactcagca gccctcatat aataggtttg aaagtactcc taaaataaa acactgtttc 46321 cctttggaac tatttacaaggatgaaacaa ccgtatacct gagaaataac ttgctctggt 46381 gtcaattcgc tattcgccag cagacatcag aacacaccga gtttccagat gctggttttt 46441 ccccttaaat caggaaatac acctggacaa tttctagaag actacaattc agtctagcca 46501 caaaggggat tttttttttt tggtaacagg ctagagcccg gttctgtaag tctttagctg 46561 aaatggtcca gtacaaaagc actggaaatg agtgggctag gaggacaagg accgtctcct 46621 gcgtgaggag ttggttggag gtccccaagg ccaggtaccc cctgcactct tattggattc 46681 ctctctgtct tcttggagtt ttgaaaaact ccttcgaaca ccaggctttt ttctttagaa 46741 aacaagtctc caatcgttct ctgttccgta gaaagagaaa gaaaacctgg agcagctgct 46801 gaaaaatcta atgaggaact aagaggcaaa cccacca

[00117] A non-limiting example of a wild-type human CLRN1 genomic DNA sequence is SEQ ID NO: 9. The exons in SEQ ID NO: 9 are: nucleotide positions 1-544 (exon 1), nucleotide positions 28764-29180 (exon 2), nucleotide positions 31239-31418 (exon 3), nucleotide positions 32481-32519 (exon 4), nucleotide positions 44799-46433 (exon 5), positions of Petition 870260061675, dated 06 / 23 / 2026, page 120 / 935 113 / 362 nucleotide positions 44799-44935 (exon 6) and nucleotide positions 4612846837 (exon 7). The introns are located between each pair of these exons in SEQ ID NO: 9, namely, at nucleotide positions 54528763 (intron 1), nucleotide positions 29181-31238 (intron 2), nucleotide positions 31419-32480 (intron 3), nucleotide positions 32520-44798 (intron 4), and nucleotide positions 44936-46127 (intron 7). Mouse CLRN1 Protein Isoform 1 (SEQ ID NO: 10) MPSQQKKIIFCMAGVLSFLCALGVVTAVGTPLWVKATILCKTGALLVN ASGKELDKFMGEMQYGLFHGEGVRQCGLGARPFRFSSRSMKERYS LYEDKGETAVFPDLVQAIPVSIHINIILFSMILVVLTMVGTAFFMYNAFG KPFETLHGPLGLYLVSFISGSCGCLVMILFASEVKVHRLSEKIANFKEG TYAYRTQNENYTTSFWVVFICFFVHFLNGLLIRLAGFQFPFTKSKETE TTNVASDLMY Dog CLRN1 protein (SEQ ID NO: 11) MPNQQKKVVFCTAGVLSFVCALGVVTALGTPLWIKATFLCKTGALLV NASGQELDKFMGEMQYGLFHGEGIRQCGLGARPFRFSLFPDLLKVIP VSIHVNVILFSTILVVLTMVGTAFFMYNAFGKPFETLHGPLGLYLLSFIS GSCGCLVMILFASEVKIHHLSEKIANYKEGTYAYKTQSEKYTTSFWVV FICFLVHLLNGLLIRLAGFQFPFAKS KDTETTNVAADLMY Vectors

[00118] The compositions provided in this document include at least two (e.g., two, three, four, five, or six) nucleic acid vectors, wherein: each of the at least two different vectors includes a coding sequence that encodes a different portion of a CLRN1 protein, each of the encoded portions having at least 30 amino acids (e.g., from about 30 amino acids to about 202 amino acids, from about 30 amino acids to about 200 amino acids, from about 30 amino acids to about 180 amino acids, from about 30 amino acids to about 170 amino acids, Petition 870260061675, dated 06 / 23 / 2026, p. 121 / 935 114 / 362 from approximately 30 amino acids to approximately 160 amino acids, from approximately 30 amino acids to approximately 150 amino acids, from approximately 30 amino acids to approximately 140 amino acids, from approximately 30 amino acids to approximately 130 amino acids, from approximately 30 amino acids to approximately 120 amino acids, from approximately 30 amino acids to approximately 110 amino acids, from approximately 30 amino acids to approximately 100 amino acids, from approximately 30 amino acids to approximately 90 amino acids, from approximately 30 amino acids to approximately 80 amino acids, from approximately 30 amino acids to approximately 70 amino acids, from approximately 30 amino acids to approximately 60 amino acids, from approximately 30 amino acids to approximately 50 amino acids, from approximately 30 amino acids to approximately 40 amino acids, from approximately 60 amino acids to approximately 202 amino acids, from approximately 60 amino acids to approximately 200 amino acids, from approximately 60 amino acids to approximately 180 amino acids, from approximately 60 amino acids to approximately 170 amino acids, approximately 60 amino acids to approximately 160 amino acids, approximately 60 amino acids to approximately 150 amino acids,from approximately 60 amino acids to approximately 140 amino acids, from approximately 60 amino acids to approximately 130 amino acids, from approximately 60 amino acids to approximately 120 amino acids, from approximately 60 amino acids to approximately 110 amino acids, from approximately 60 amino acids to approximately 100 amino acids, from approximately 60 amino acids to approximately 90 amino acids, from approximately 60 amino acids to approximately 80 amino acids, from approximately 60 amino acids to approximately 70 amino acids, from approximately 90 amino acids to approximately 202 amino acids, from approximately 90 amino acids to approximately 200 amino acids, from approximately 90 amino acids to approximately 180 amino acids, from approximately 90 amino acids to approximately 170 amino acids, from approximately 90 amino acids to approximately 160 amino acids, from approximately 90 amino acids to approximately 150 amino acids, from approximately 90 amino acids to approximately 140 amino acids, from approximately 90 amino acids to approximately 130 amino acids, from approximately 90 amino acids to approximately 120 amino acids, approximately 90 amino acids to approximately 110 amino acids, approximately 90 amino acids to approximately 100 amino acids, Petition 870260061675, dated 06 / 23 / 2026, p. 122 / 935 115 / 362 from approximately 100 amino acids to approximately 202 amino acids, from approximately 100 amino acids to approximately 200 amino acids, from approximately 100 amino acids to approximately 180 amino acids, from approximately 100 amino acids to approximately 170 amino acids, from approximately 100 amino acids to approximately 160 amino acids, from approximately 100 amino acids to approximately 150 amino acids, from approximately 100 amino acids to approximately 140 amino acids, from approximately 100 amino acids to approximately 130 amino acids, from approximately 100 amino acids to approximately 120 amino acids, from approximately 90 amino acids to approximately 110 amino acids, from approximately 120 amino acids to approximately 202 amino acids, from approximately 120 amino acids to approximately 200 amino acids, from approximately 120 amino acids to approximately 180 amino acids, from approximately 120 amino acids to approximately 170 amino acids, from approximately 120 amino acids to approximately 160 amino acids, from about 120 amino acids to about 150 amino acids, from about 120 amino acids to about 140 amino acids, from about 120 amino acids to about 130 amino acids,about 150 amino acids to about 202 amino acids, about 150 amino acids to about 200 amino acids, about 150 amino acids to about 180 amino acids, about 150 amino acids to about 170 amino acids, about 150 amino acids to about 160 amino acids, about 170 amino acids to about 202 amino acids, about 170 amino acids to about 200 amino acids, about 170 amino acids to about 180 amino acids, about 190 amino acids to about 202 amino acids, or about 190 amino acids to about 200 amino acids) long.

[00119] In some embodiments of these compositions, at least one of the coding sequences includes a nucleotide sequence spanning two consecutive exons of CLRN1 genomic DNA (e.g., exons 1 and 2, or exons 5 and 6), and without the intronic sequence that naturally occurs between the two consecutive exons.

[00120] In some embodiments, the amino acid sequence of none of the encoded portions overlaps, not even in part, Petition 870260061675, dated 06 / 23 / 2026, p. 123 / 935 116 / 362 to the amino acid sequence of one of the different coded portions. In some embodiments, the amino acid sequence of one or more of the coded portions partially overlaps with the amino acid sequence of one of the different coded portions. In some embodiments, the amino acid sequence of each of the coded portions partially overlaps with the amino acid sequence of a different coded portion.

[00121] In some embodiments, the overlapping amino acid sequence is about 30 amino acid residues and about 202 amino acids (for example, or any of the subranges of this range described in this document) in length.

[00122] In some examples, the vectors include two different vectors, each comprising a different segment of an intron, wherein the intron includes the nucleotide sequence of an intron that is present in a CLRN1 genomic DNA (e.g., any of the exemplary introns in SEQ ID NO: 9 described in this document), and wherein the two different segments overlap in sequence by at least 100 nucleotides (e.g., approximately 100 nucleotides to approximately 10,000 nucleotides, approximately 100 nucleotides to approximately 5,000 nucleotides, approximately 100 nucleotides to approximately 4,500 nucleotides, approximately 100 nucleotides to approximately 4,000 nucleotides, approximately 100 nucleotides to approximately 3,500 nucleotides, approximately 100 nucleotides to approximately 3,000 nucleotides, approximately 100 nucleotides to approximately 2,500 nucleotides, approximately 100 nucleotides to approximately 2,000 nucleotides, approximately 100 nucleotides to approximately 1.500 nucleotides, approximately 100 nucleotides to approximately 1,000 nucleotides, approximately 100 nucleotides to approximately 800 nucleotides, approximately 100 nucleotides to approximately 600 nucleotides, approximately 100 nucleotides to approximately 400 nucleotides, approximately 100 nucleotides to approximately 200 nucleotides, approximately 200. Petition 870260061675, dated 06 / 23 / 2026, page 124 / 935 117 / 362 nucleotides to approximately 10,000 nucleotides, approximately 200 nucleotides to approximately 5,000 nucleotides, approximately 200 nucleotides to approximately 4,500 nucleotides, approximately 200 nucleotides to approximately 4,000 nucleotides, approximately 200 nucleotides to approximately 3,500 nucleotides, approximately 200 nucleotides to approximately 3,000 nucleotides, approximately 200 nucleotides to approximately 2,500 nucleotides, approximately 200 nucleotides to approximately 2,000 nucleotides, approximately 200 nucleotides to approximately 1,500 nucleotides, approximately 200 nucleotides to about 1,000 nucleotides, about 200 nucleotides to about 800 nucleotides, about 200 nucleotides to about 600 nucleotides, about 200 nucleotides to about 400 nucleotides, about 400 nucleotides to about 10,000 nucleotides, about 400 nucleotides to about 5,000 nucleotides, about 400 nucleotides to about 4,500 nucleotides, about 400 nucleotides to about 4,000 nucleotides, about 400 nucleotides to about 3.500 nucleotides, approximately 400 nucleotides to approximately 3,000 nucleotides, approximately 400 nucleotides to approximately 2,500 nucleotides, approximately 400 nucleotides to approximately 2,000 nucleotides, approximately 400 nucleotides to approximately 1,500 nucleotides, approximately 400 nucleotides to approximately 1,000 nucleotides, approximately 400 nucleotides to approximately 800 nucleotides, approximately 400 nucleotides to approximately 600 nucleotides, approximately 600 nucleotides to approximately 10,000 nucleotides, approximately 600 nucleotides to approximately 5,000 nucleotides, approximately 600 nucleotides to about 4,500 nucleotides, about 600 nucleotides to about 4,000 nucleotides, about 600 nucleotides to about 3,500 nucleotides, about 600 nucleotides to about 3,000 nucleotides, about 600 nucleotides to about 2,500 nucleotides, about 600 nucleotides to about 2,000 nucleotides, about 600 nucleotides to about 1,500 nucleotides, about 600 nucleotides to about 1.000 nucleotides, approximately 600 nucleotides, approximately. Petition 870260061675, dated 06 / 23 / 2026, page 125 / 935 118 / 362 800 nucleotides, approximately 800 nucleotides to approximately 10,000 nucleotides, approximately 800 nucleotides to approximately 5,000 nucleotides, approximately 800 nucleotides to approximately 4,500 nucleotides, approximately 800 nucleotides to approximately 4,000 nucleotides, approximately 800 nucleotides to approximately 3,500 nucleotides, approximately 800 nucleotides to approximately 3,000 nucleotides, approximately 800 nucleotides to approximately 2,500 nucleotides, approximately 800 nucleotides to approximately 2,000 nucleotides, approximately 800 nucleotides to approximately 1,500 nucleotides, approximately from 800 nucleotides to about 1,000 nucleotides, from about 1,000 nucleotides to about 10,000 nucleotides, from about 1,000 nucleotides to about 5,000 nucleotides, from about 1,000 nucleotides to about 4,500 nucleotides, from about 1,000 nucleotides to about 4,000 nucleotides, from about 1,000 nucleotides to about 3,500 nucleotides, from about 1,000 nucleotides to about 3,000 nucleotides, from about 1,000 nucleotides to about 2.500 nucleotides, approximately 1,000 nucleotides to approximately 2,000 nucleotides, approximately 1,000 nucleotides to approximately 1,500 nucleotides, approximately 1,500 nucleotides to approximately 10,000 nucleotides, approximately 1,500 nucleotides to approximately 5,000 nucleotides, approximately 1,500 nucleotides to approximately 4,500 nucleotides, approximately 1,500 nucleotides to approximately 4,000 nucleotides, approximately 1,500 nucleotides to approximately 3,500 nucleotides, approximately 1,500 nucleotides to approximately 3,000 nucleotides, approximately 1,500 nucleotides to about 2,500 nucleotides, about 1,500 nucleotides to about 2,000 nucleotides, about 2,000 nucleotides to about 10,000 nucleotides, about 2,000 nucleotides to about 5,000 nucleotides, about 2,000 nucleotides to about 4,500 nucleotides, about 2,000 nucleotides to about 4,000 nucleotides, about 2,000 nucleotides to about 3,500 nucleotides, about 2,000 nucleotides to about 3,000 nucleotides, about 2.000 nucleotides to approximately 2,500 nucleotides. Petition 870260061675, dated 06 / 23 / 2026, page 126 / 935 119 / 362 nucleotides, approximately 2,500 to approximately 10,000 nucleotides, approximately 2,500 to approximately 5,000 nucleotides, approximately 2,500 to approximately 4,500 nucleotides, approximately 2,500 to approximately 4,000 nucleotides, approximately 2,500 to approximately 3,500 nucleotides, approximately 2,500 to approximately 3,000 nucleotides, approximately 3,000 to approximately 10,000 nucleotides, approximately 3,000 to approximately 5,000 nucleotides, approximately 3,000 nucleotides to about 4,500 nucleotides, about 3,000 nucleotides to about 4,000 nucleotides, about 3,000 nucleotides to about 3,500 nucleotides, about 3,500 nucleotides to about 10,000 nucleotides, about 3,500 nucleotides to about 5,000 nucleotides, about 3,500 nucleotides to about 4,500 nucleotides, about 3,500 nucleotides to about 4,000 nucleotides, about 4,000 nucleotides to about 10,000 nucleotides, about 4.000 nucleotides to about 5,000 nucleotides, about 4,000 nucleotides to about 4,500 nucleotides, about 4,500 nucleotides to about 10,000 nucleotides, about 4,500 nucleotides to about 5,000 nucleotides, or about 5,000 nucleotides to about 10,000 nucleotides) in length.

[00123] The overlapping nucleotide sequence in any two of the different vectors may include part or all of one or more exons of a CLRN1 gene (for example, any one or more of the exemplary exons in SEQ ID NO: 9 described in this document).

[00124] In some embodiments, the number of different vectors in the composition is two, three, four, or five. In compositions where the number of different vectors in the composition is two, the first of the two different vectors may include a coding sequence that encodes an N-terminal portion of the CLRN1 protein. In some examples, the N-terminal portion of the CLRN1 gene is about 30 amino acids long. Petition 870260061675, dated 06 / 23 / 2026, p. 127 / 935 120 / 362 amino acids of approximately 202 amino acids (or any of the subranges of this range described above) in length. In some examples, the first vector further includes one or both of a promoter (e.g., any of the promoters described in this document or known in the art) and a Kozak sequence (e.g., any of the exemplary Kozak sequences described in this document or known in the art). In some examples, the first vector includes a promoter that is an inducible promoter, a constitutive promoter, or a tissue-specific promoter. In some examples, the second of the two different vectors includes a coding sequence that encodes a C-terminal portion of the CLRN1 protein. In some examples, the C-terminal portion of the CLRN1 protein is from 30 amino acids to approximately 202 amino acids (or any of the subranges of this range described above) in length.In some examples, the second vector also includes a polyadenylation signal sequence.

[00125] In some examples where the number of different vectors in the composition is two, the N-terminal portion encoded by one of the two vectors may include a portion comprising amino acid position 1 to any of the following: around amino acid position 202, around amino acid position 200, around amino acid position 190, around amino acid position 180, around amino acid position 170, around amino acid position 160, around amino acid position 150, around amino acid position 140, around amino acid position 130, around amino acid position 120, around amino acid position 110, around amino acid position 100, around amino acid position 90, around amino acid position 80, around amino acid position 70, around amino acid position 60, around from amino acid 50 or around the position of amino acid 40 Petition 870260061675, dated 06 / 23 / 2026, p. 128 / 935 121 / 362 of a wild-type CLRN1 protein (e.g., SEQ ID NO: 1, 3, 5, or 7).

[00126] In some examples where the number of different vectors in the composition is two, the N-terminal portion of the CLRN1 precursor protein may include a portion comprising from amino acid position 1 to amino acid position 202, from amino acid position 1 to approximately amino acid position 200, from amino acid position 1 to approximately amino acid position 190, from amino acid position 1 to approximately amino acid position 180, from amino acid position 1 to approximately amino acid position 170, from amino acid position 1 to approximately amino acid position 160, from amino acid position 1 to approximately amino acid position 150, from amino acid position 1 to approximately amino acid position 140, from amino acid position 1 to approximately amino acid position 130, from amino acid position 1 to approximately amino acid position 120, from amino acid position 1 up to approximately amino acid position 110,from amino acid position 1 to approximately amino acid position 100, from amino acid position 1 to approximately amino acid position 90, from amino acid position 1 to approximately amino acid position 80, from amino acid position 1 to approximately amino acid position 70, from amino acid position 1 to approximately amino acid position 60, from amino acid position 1 to approximately amino acid position 50, from amino acid position 1 to approximately amino acid position 40, from amino acid position 1 to approximately amino acid position 30 of a wild-type CLRN1 protein (e.g., SEQ ID NO: 1, 3, 5, or 7). As used in this document, the term vector means a composition that includes a polynucleotide capable of carrying at least one exogenous nucleic acid fragment, for example, a plasmid vector, a transposon, a cosmid, an artificial chromosome (e.g., a... Petition 870260061675, dated 06 / 23 / 2026, page 129 / 935 122 / 362 human artificial chromosome (HAC), a yeast artificial chromosome (YAC), a bacterial artificial chromosome (BAC), or a P1-derived artificial chromosome (PAC)), a viral vector (e.g., any adenoviral vectors (e.g., pSV or pCMV vectors) or any retroviral vectors as described in this document), and any Gateway® vectors. A vector may, for example, include sufficient cis-acting elements for expression; other elements for expression may be provided by the mammalian host cell or in an in vitro expression system. The term vector includes any genetic element (e.g., a plasmid, a transposon, a cosmid, an artificial chromosome, a viral vector, etc.) that is capable of replicating when associated with the appropriate control elements.Thus, the term includes cloning and expression vectors, as well as viral vectors (e.g., an adeno-associated virus (AAV) vector, an adenovirus vector, a lentivirus vector, or a retrovirus vector).

[00127] Vectors include all those known in the art, including cosmids, plasmids (e.g., naked or contained in liposomes), and viruses (e.g., lentiviruses, retroviruses, adenoviruses, and adeno-associated viruses) that incorporate recombinant polynucleotides. Qualified physicians will be able to select suitable mammalian vectors and cells for the production of any of the nucleic acids described in this document. In some embodiments, the vector is a plasmid (i.e., a circular DNA molecule that can replicate autonomously within a cell). In some embodiments, the vector may be a cosmid (e.g., the pWE and sCos series (Wahl et al. (1987), Evans et al. (1989))).

[00128] In some embodiments, the vector(s) is / are an artificial chromosome. An artificial chromosome is a genetically manipulated chromosome that can be used as a vector for trans Petition 870260061675, dated 06 / 23 / 2026, p. 130 / 935 123 / 362 carry large DNA insertions. In some embodiments, the artificial chromosome is a human artificial chromosome (HAC) (see, for example, Kouprina et al., Expert Opin. Drug Deliv 11(4): 517-535, 2014; Basu et al., Pediatr. Clin. North Am. 53: 843-853, 2006; Ren et al., Stem. Cell Rev. 2(1):43-50, 2006; Kazuki et al., Mol.

[00129] In some embodiments, the vector(s) is / are a yeast artificial chromosome (YAC) (see, for example, Murray et al., Nature 305: 189-193, 1983; Ikeno et al. (1998) Nat. Biotech. 16:431439, 1998). In some embodiments, the vector(s) is / are a bacterial artificial chromosome (BAC) (for example, pBeloBAC11, pECBAC1 and pBAC108L). In some embodiments, the vector(s) is / are a P1-derived artificial chromosome (PAC). Examples of artificial chromosomes are known in the art.

[00130] In some embodiments, the vector(s) is / are a viral vector (e.g., adeno-associated virus, adenovirus, lentivirus, and retrovirus). Non-limiting examples of viral vectors are described in this document. In some embodiments, the vector(s) is / are an adeno-associated viral vector (AAV) (see, for example, Asokan et al., Mol. Ther. 20: 699-7080, 2012). Recombinant AAV vectors, or rAAVs, are typically composed of at least one transgene, or a portion thereof, and a regulatory sequence and, optionally, 5' and 3' AAV inverted terminal repeats (ITRs). This recombinant AAV vector is packaged in a capsid and delivered to a selected target cell (e.g., a cochlear hair cell).

[00131] Vector AAV sequences typically comprise the 5' and 3' cis action ITR sequences (See, for example, BJ Carter, in Handbook of Parvoviruses, ed., P. Tijsser, CRC Press, pp. 155-168, 1990). Typical AAV ITR sequences are approximately Petition 870260061675, dated 06 / 23 / 2026, p. 131 / 935 124 / 362 145 nucleotides in length. In some embodiments, at least 75% of a typical ITR sequence (e.g., at least 80%, at least 85%, at least 90%, or at least 95%) is incorporated into the AAV vector. The ability to modify these ITR sequences is within the capability of the technique. (See, for example, texts such as Sambrook et al., Molecular Cloning. A Laboratory Manual, 2nd ed., Cold Spring Harbor Laboratory, New York, 1989; and K. Fisher et al., J Virol. 70:520-532, 1996). In some embodiments, any of the coding sequences described in this document is flanked by 5' and 3' AAV ITR sequences in the AAV vectors. AAV ITR sequences can be obtained from any known AAV, including currently identified AAV types.

[00132] The AAV vectors as described in this document may include any of the regulatory elements described in this document (e.g., one or more of a promoter, a polyadenylation signal sequence (poly(A)) and an IRES).

[00133] In some embodiments, the AAV vector is selected from the group consisting of: an AAV1 vector, an AAV2 vector, an AAV3 vector, an AAV4 vector, an AAV5 vector, an AAV6 vector, an AAV7 vector, an AAV8 vector, an AAV9 vector, an AAV2.7m8 vector, an AAV8BP2 vector, and an AAV293 vector. Additional exemplary AAV vectors that may be used in this document are known in the art. See, for example, Kanaan et al., Mol. Ther. Nucleic Acids 8:184-197, 2017; Li et al., Mol. Ther. 16(7): 1252-1260; Adachi et al., Nat. Commun. 5: 3075, 2014; Isgrig et al., Nat. Commun. 10(1): 427, 2019; and Gao et al., J. Virol. 78(12): 6381-6388.

[00134] In some embodiments, an AAV vector provided in this document includes or consists of a sequence that is at least 80% identical (e.g., at least 82%, at least 84%, by Petition 870260061675, dated 06 / 23 / 2026, p. 132 / 935 125 / 362 less 85%, at least 86%, at least 88%, at least 90%, at least 92%, at least 94%, at least 95%, at least 96%, at least 98%, at least 99% or 100% identical) to SEQ ID NO: 40, 41, 42, 43, 44, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 or 60. In some embodiments, the vector(s) is / are an adenovirus (see, for example, Dmitriev et al. (1998) J. Virol. 72: 9706-9713; and Poulin et al., J. Virol 8: 10074-10086, 2010). In some forms, the vector(s) is / are a retrovirus (see, for example, Maier et al. (2010) Future Microbiol 5: 1507-23).

[00135] In some embodiments, the vector(s) is / are a lentivirus (see, for example, Matrai et al. (2010) Mol Ther. 18: 477-490; Banasik et al. (2010) Gene Ther. 17:150-7; and Wanisch et al. (2009) Mol. Ther. 17: 1316-32). A lentiviral vector refers to a vector derived from at least a portion of a lentivirus genome, including, in particular, a self-inactivating lentiviral vector as described in Milone et al., Mol. Ther. 17(8): 1453-1464 (2009). Non-limiting lentivirus vectors that can be used clinically include Oxford BioMedica's LENTIVECTOR® gene delivery technology, Lentigen's LENTIMAX™ vector system, and similar devices. Other types of lentiviral vectors are also available and would be known to a person skilled in the art.

[00136] The vectors provided in this document may have different sizes. The choice of which vector is used in any of the compositions, kits, and methods described in this document may depend on the size of the vector.

[00137] In some embodiments, the vector(s) is / are a plasmid and may include a total length of up to about 1 kb, up to about 2 kb, up to about 3 kb, up to about 4 kb, up to about 5 kb, up to about 6 kb, up to about 7 kb, up to about 8 kb, up to about 9 kb, up to about 10 kb, up to about 11 kb, up to about 12 kb, up to Petition 870260061675, dated 06 / 23 / 2026, p. 133 / 935 126 / 362 approximately 13 kb, up to approximately 14 kb or up to approximately 15 kb. In some embodiments, the vector(s) is / are a plasmid and may have a total length in the range of about 1 kb to about 2 kb, about 1 kb to about 3 kb, about 1 kb to about 4 kb, about 1 kb to about 5 kb, about 1 kb to about 6 kb, about 1 kb to about 7 kb, about 1 kb to about 8 kb, about 1 kb to about 9 kb, about 1 kb to about 10 kb, about 1 kb to about 11 kb, about 1 kb to about 12 kb, about 1 kb to about 13 kb, about 1 kb to about 14 kb, or about 1 kb to about 15 kb.

[00138] In some embodiments, the vector(s) is / are a transposon (e.g., PiggyBac™ transposon) and may include more than 200 kb. In some examples, the vector(s) is / are a transposon with a total length in the range of about 1 kb to about 10 kb, about 1 kb to about 20 kb, about 1 kb to about 30 kb, about 1 kb to about 40 kb, about 1 kb to about 50 kb, about 1 kb to about 60 kb, about 1 kb to about 70 kb, about 1 kb to about 80 kb, about 1 kb to about 90 kb, about 10 kb to about 20 kb, about 10 kb to about 30 kb, about 10 kb to about 40 kb, about 10 kb to about 50 kb, about 10 kb to about 60 kb, about 10 kb to about 70 kb, about 10 kb to about 40 kb, about 10 kb to about 100 kb, about 20 kb to about 30 kb, about 20 kb to about 40 kb, about 20 kb to about 50 kb, about 20 kb to about 60 kb, about 20 kb to about 70 kb, about 20 kb to about 80 kb,approximately 20 kb to approximately 90 kb, approximately 20 kb to approximately 100 kb, approximately 30 kb to approximately 40 kb, approximately 30 kb to approximately 50 kb, approximately 30 kb to approximately 60 kb, approximately 30 kb to approximately 70 kb, approximately 30 kb to approximately 80 kb, approximately 30 kb to approximately 90 kb, approximately 30 kb to approximately 100 kb, approximately 40 kb to approximately 50 kb, approximately 40 kb to approximately 60 kb, approximately 40 kb to approximately 70 kb, approximately 40 kb to approximately 80 kb, approximately 40 kb to approximately Petition 870260061675, dated 06 / 23 / 2026, page. 134 / 935 127 / 362 from 90 kb, about 40 kb to about 100 kb, about 50 kb to about 60 kb, about 50 kb to about 70 kb, about 50 kb to about 80 kb, about 50 kb to about 90 kb, about 50 kb to about 100 kb, about 60 kb to about 70 kb, about 60 kb to about 80 kb, about 60 kb to about 90 kb, about 60 kb to about 100 kb, about 70 kb to about 80 kb, about 70 kb to about 90 kb, about 70 kb to about 100 kb, about 80 kb to about 90 kb, about 80 kb to about 100 kb, about 90 kb to about 100 kb, about 1 kb to about 100 kb, about 100 kb to about 200 kb, about 100 kb to about 300 kb, about 100 kb to about 400 kb or about 100 kb to about 500 kb.

[00139] In some forms, the vector is a cosmid and can have a total length of up to 55 kb. In some examples, the vector is a cosmid and has a total number of nucleotides of approximately 1 kb to approximately 10 kb, approximately 1 kb to approximately 20 kb, approximately 1 kb to approximately 30 kb, approximately 1 kb to approximately 40 kb, approximately 1 kb to approximately 50 kb, approximately 1 kb to approximately 55 kb, approximately 10 kb to approximately 20 kb, approximately 10 kb to approximately 30 kb, approximately 10 kb to approximately 40 kb, approximately 10 kb to approximately 50 kb, approximately 10 kb to approximately 55 kb, approximately 15 kb to approximately 55 kb, approximately 15 kb to approximately 50 kb, approximately 15 kb to approximately 40 kb, approximately 15 kb to about 30 kb, about 20 kb to about 20 kb, about 20 kb to about 55 kb, about 20 kb to about 50 kb, about 20 kb to about 40 kb, about 20 kb to about 30 kb, about 25 kb to about 55 kb, about 25 kb to about 50 kb kb, about 25 kb to about 40 kb, about 25 kb to about 30 kb, about 30 kb to about 55 kb,about 30 kb to about 40 kb, about 30 kb to about 40 kb, about 35 kb to about 55 kb, about 40 kb to about 55 kb, about 40 kb to about 50 kb or about 45 kb to about 55 kb.

[00140] In some modalities, the vector(s) is / are a croPetition 870260061675, dated 06 / 23 / 2026, p. 135 / 935 128 / 362 artificial monosome and may have a total number of nucleotides from about 100 kb to about 2,000 kb. In some embodiments, the artificial chromosome(s) is / are a human artificial chromosome (HAC) and may have a total number of nucleotides in the range of about 1 kb to about 10 kb, 1 kb to about 20 kb, about 1 kb to about 30 kb, about 1 kb to about 40 kb, about 1 kb to about 50 kb, about 1 kb to about 60 kb, about 10 kb to about 20 kb, about 10 kb to about 30 kb, about 10 kb to about 40 kb, about 10 kb to about 50 kb, about 10 kb to about 60 kb, about 20 kb to about 30 kb, about 20 kb to about 40 kb, about 20 kb to about 50 kb, about 20 kb to about 60 kb, about 40 kb to about 40 kb, about 30 kb to about 50 kb, about 30 kb to about 60 kb, about 40 kb to about 50 kb, about 40 kb to about 60 kb or about 50 kb to about 60 kb.

[00141] In some embodiments, the artificial chromosome(s) is / are a yeast artificial chromosome (YAC) and may have a total number of nucleotides of up to 1000 kb. In some embodiments, the artificial chromosome(s) is / are a YAC with a total number of nucleotides in the range of approximately 100 kb to approximately 1,000 kb, approximately 100 kb to approximately 900 kb, approximately 100 kb to approximately 800 kb, approximately 100 kb to approximately 700 kb, approximately 100 kb to approximately 600 kb, approximately 100 kb to approximately 500 kb, approximately 100 kb to approximately 400 kb, approximately 100 kb to approximately 300 kb, approximately 100 kb to approximately 200 kb, approximately 200 kb to approximately 1,000 kb, approximately 200 kb to approximately 900 kb, approximately 200 kb to about 800 kb, about 200 kb to about 700 kb, about 200 kb to about 600 kb, about 200 kb to about 500 kb, about 200 kb to about 400 kb, about 200 kb to about 300 kb, about 300 kb to about 1.000 kb, about 300 kb to about 900 kb, about 300 kb to about 800 kb, about 300 kb to about 700 kb, about 300 kb to about 600 kb, about 300 kb to about. Petition 870260061675, dated 06 / 23 / 2026, p. 136 / 935 129 / 362 500 kb, approximately 300 kb to approximately 400 kb, approximately 400 kb to approximately 1,000 kb, approximately 400 kb to approximately 900 kb, approximately 400 kb to approximately 800 kb, approximately 400 kb to approximately 700 kb, approximately 400 kb to approximately 600 kb, approximately 400 kb to approximately 500 kb, approximately 500 kb to approximately 1,000 kb, approximately 500 kb to approximately 900 kb, approximately 500 kb to approximately 800 kb, approximately 500 kb to approximately 700 kb, approximately 500 kb to approximately 600 kb, approximately 600 kb to approximately 1,000 kb, about 600 kb to about 900 kb, about 600 kb to about 800 kb, about 600 kb to about 700 kb, about 700 kb to about 1,000 kb, about 700 kb to about 900 kb, about 700 kb to about 800 kb, about 800 kb to about 1,000 kb, about 800 kb to about 900 kb or about 900 kb to about 1,000 kb.

[00142] In some embodiments, the artificial chromosome(s) is / are a bacterial artificial chromosome (BAC) and may have a total number of nucleotides of up to 750 kb. In some embodiments, the artificial chromosome(s) is / are a BAC and may have a total number of nucleotides in the range of approximately 100 kb to approximately 750 kb, approximately 100 kb to approximately 700 kb, approximately 100 kb to approximately 600 kb, approximately 100 kb to approximately 500 kb, approximately 100 kb to approximately 400 kb, approximately 100 kb to approximately 300 kb, approximately 100 kb to approximately 200 kb, approximately 150 kb to approximately 750 kb, approximately 150 kb to approximately 700 kb, approximately 150 kb to approximately 600 kb, approximately 150 kb to approximately 500 kb, approximately 150 kb to approximately 400 kb, about 150 kb to about 300 kb, about 150 kb to about 200 kb, about 200 kb to about 750 kb, about 200 kb to about 700 kb, about 200 kb to about 600 kb, about 200 kb to about 500 kb, about 200 kb to about 400 kb, about 200 kb to about 300 kb,approximately 250 kb to approximately 750 kb, approximately 250 kb to approximately 700 kb, approximately 250 kb to approximately 600 kb, approximately 250 kb to approximately 500 kb, approximately 250 kb to approximately 400 kb, approximately 250 kb to approximately 300 kb, approximately 300 kb to approximately 750 kb Petition 870260061675, dated 06 / 23 / 2026, page. 137 / 935 130 / 362 kb, approximately 300 kb to approximately 700 kb, approximately 300 kb to approximately 600 kb, approximately 300 kb to approximately 500 kb, approximately 300 kb to approximately 400 kb, approximately 350 kb to approximately 750 kb, approximately 350 kb to approximately 700 kb, approximately 350 kb to approximately 600 kb, approximately 350 kb to approximately 500 kb, approximately 350 kb to approximately 400 kb, approximately 400 kb to approximately 750 kb, approximately 400 kb to approximately 700 kb, approximately 450 kb to approximately 600 kb, approximately 450 kb to approximately 500 kb, approximately 500 kb to approximately 750 kb, approximately 500 kb to approximately 700 kb, approximately 500 kb to approximately 600 kb, about 550 kb to about 750 kb, about 550 kb to about 700 kb, about 550 kb to about 600 kb, about 600 kb to about 750 kb, about 600 kb to about 700 kb, or about 650 kb to about 750 kb.

[00143] In some embodiments, the artificial chromosome(s) is / are a P1-derived artificial chromosome (PAC) and may have a total number of nucleotides of up to 300 kb. In some embodiments, the P1-derived artificial chromosome(s) may have a total number of nucleotides in the range of about 100 kb to about 300 kb, about 100 kb to about 200 kb, or about 200 kb to about 300 kb.

[00144] In some embodiments, the vector(s) is / are a viral vector that may have a total number of nucleotides of up to 10 kb. In some embodiments, the viral vector(s) may have a total number of nucleotides in the range of approximately 1 kb to approximately 2 kb, 1 kb to approximately 3 kb, approximately 1 kb to approximately 4 kb, approximately 1 kb to approximately 5 kb, approximately 1 kb to approximately 6 kb, approximately 1 kb to approximately 7 kb, approximately 1 kb to approximately 8 kb, approximately 1 kb to approximately 9 kb, approximately 1 kb to approximately 10 kb, approximately 2 kb to approximately 3 kb, approximately 2 kb to approximately 4 kb, approximately 2 kb to approximately 5 kb, approximately 2 kb to approximately 6 kb, approximately 2 kb to approximately 7 kb, approximately 2 kb to approximately 8 kb, approximately 2 kb to about 9 kb, about 2 kb to about 10 kb, about Petition 870260061675, dated 06 / 23 / 2026, p. 138 / 935 131 / 362 from 3 kb to about 4 kb, about 3 kb to about 5 kb, about 3 kb to about 6 kb, about 3 kb to about 7 kb, about 3 kb to about 8 kb, about 3 kb to about 9 kb, about 3 kb to about 10 kb, about 4 kb to about 5 kb, about 4 kb to about 6 kb, about 4 kb to about 7 kb, about 4 kb to about 8 kb, about 4 kb to about 9 kb, about 4 kb to about 10 kb, about 5 kb to about 6 kb, about 5 kb to about 7 kb, about 5 kb to about 8 kb, about 5 kb to about 9 kb, about 5 kb to about 10 kb, about 6 kb to about 7 kb, about 6 kb to about 8 kb, about 6 kb to about 9 kb, about 6 kb to about 10 kb, about 7 kb to about 8 kb, about 7 kb to about 9 kb, about 7 kb to about 10 kb, about 8 kb to about 9 kb, about 8 kb to about 10 kb, or about 9 kb to about 10 kb.

[00145] In some embodiments, the vector(s) is / are a lentivirus and may have a total number of nucleotides of up to 8 kb.In some examples, the lentivírus could have a total number of nucleotides of approximately 1 kb to approximately 2 kb, approximately 1 kb to approximately 3 kb, approximately 1 kb to approximately 4 kb, approximately 1 kb to approximately 5 kb, approximately 1 kb to approximately 6 kb, approximately 1 kb to approximately 7 kb, approximately 1 kb to approximately 8 kb, approximately 2 kb to approximately 3 kb, approximately 2 kb to approximately 4 kb, approximately 2 kb to approximately 5 kb, approximately 2 kb to approximately 6 kb, approximately 2 kb to approximately 7 kb, approximately 2 kb to approximately 8 kb, approximately 3 kb to approximately 4 kb, approximately 3 kb to approximately 5 kb, approximately 3 kb to approximately from 6 kb, about 3 kb to about 7 kb, about 3 kb to about 8 kb, about 4 kb to about 5 kb, about 4 kb to about 6 kb, about 4 kb to about 7 kb, about 4 kb to about 8 kb, about 5 kb to about 6 kb, about 5 kb to about 7 kb, about 5 kb to about 8 kb, about 6 kb to about 8 kb, about 6 kb to about 7 kb, or about 7 kb to about 8 kb.

[00146] In some modalities, the vector(s) is / are an adeno Petition 870260061675, dated 06 / 23 / 2026, p. 139 / 935 132 / 362 viruses and may have a total number of nucleotides of up to 8 kb.In some forms, the adenovirus may have a total number of nucleotides in the range of approximately 1 kb to approximately 2 kb, approximately 1 kb to approximately 3 kb, approximately 1 kb to approximately 4 kb, approximately 1 kb to approximately 5 kb, approximately 1 kb to approximately 6 kb, approximately 1 kb to approximately 7 kb, approximately 1 kb to approximately 8 kb, approximately 2 kb to approximately 3 kb, approximately 2 kb to approximately 4 kb, approximately 2 kb to approximately 5 kb, approximately 2 kb to approximately 6 kb, approximately 2 kb to approximately 7 kb, approximately 2 kb to approximately 8 kb, approximately 3 kb to approximately 4 kb, approximately 3 kb to approximately 5 kb, approximately 3 kb to approximately 6 kb. about 3 kb to about 7 kb, about 3 kb to about 8 kb, about 4 kb to about 5 kb, about 4 kb to about 6 kb, about 4 kb to about 7 kb, about 4 kb to about 8 kb, about 5 kb to about 6 kb, about 5 kb to about 7 kb, about 5 kb to about 8 kb, about 6 kb to about 7 kb, about 6 kb to about 8 kb, or about 7 kb to about 8 kb.

[00147] In some embodiments, the vector(s) is / are an adeno-associated virus (AAV vector) and may include a total number of nucleotides of up to 5 kb. In some embodiments, the AAV vector(s) may include a total number of nucleotides in the range of about 1 kb to about 2 kb, about 1 kb to about 3 kb, about 1 kb to about 4 kb, about 1 kb to about 5 kb, about 2 kb to about 3 kb, about 2 kb to about 4 kb, about 2 kb to about 5 kb, about 3 kb to about 4 kb, about 3 kb to about 5 kb, or about 4 kb to about 5 kb.

[00148] In some embodiments, the vector(s) is / are a Gateway® vector and may include a total number of nucleotides of up to 5 kb. In some embodiments, each Gateway® vector includes a total number of nucleotides in the range of about 1 kb to about 2 kb, about 1 kb to about 3 kb, about 1 kb to about 4 kb, about 1 kb to about 5 kb, about 2 kb to about 3 kb, about 2 kb to Petition 870260061675, dated 06 / 23 / 2026, p. 140 / 935 133 / 362 about 4 kb, about 2 kb to about 5 kb, about 3 kb to about 4 kb, about 3 kb to about 5 kb or about 4 kb to about 5 kb.

[00149] In some embodiments of any of the compositions, kits, and methods provided in this document, the at least two different vectors may substantially be the same vector type and may differ in size. In some embodiments, the at least two different vectors may be different vector types and may have substantially the same size or different sizes.

[00150] In some embodiments, any one of at least two vectors may have a total number of nucleotides in the range of about 500 nucleotides to about 15,000 nucleotides, about 500 nucleotides to about 14,500 nucleotides, about 500 nucleotides to about 14,000 nucleotides, about 500 nucleotides to about 13,500 nucleotides, about 500 nucleotides to about 13,000 nucleotides, about 500 nucleotides to about 12,500 nucleotides, about 500 nucleotides to about 12,000 nucleotides, about 500 nucleotides to about 11,500 nucleotides, from about 500 nucleotides to about 11,000 nucleotides, from about 500 nucleotides to about 10,500 nucleotides, from about 500 nucleotides to about 10,000 nucleotides, from about 500 nucleotides to about 9,500 nucleotides, from about 500 nucleotides to about 9,000 nucleotides, from about 500 nucleotides to about 8.500 nucleotides, from about 500 nucleotides to about 8,000 nucleotides, from about 500 nucleotides to about 7,800 nucleotides, from about 500 nucleotides to about 7,600 nucleotides, from about 500 nucleotides to about 7,400 nucleotides, from about 500 nucleotides to about 7,200 nucleotides, from about 500 nucleotides to about 7,000 nucleotides, from about 500 nucleotides to about 6,800 nucleotides, from about 500 nu. Petition 870260061675, dated 06 / 23 / 2026, page 141 / 935 134 / 362 nucleotides to about 6,600 nucleotides, from about 500 nucleotides to about 6,400 nucleotides, from about 500 nucleotides to about 6,200 nucleotides, from about 500 nucleotides to about 6,000 nucleotides, from about 500 nucleotides to about 5,800 nucleotides, from about 500 nucleotides to about 5,600 nucleotides, from about 500 nucleotides to about 5,400 nucleotides, from about 500 nucleotides to about 5,200 nucleotides, from about 500 nucleotides to about 5,000 nucleotides, from about from 500 nucleotides to about 4,800 nucleotides, from about 4,600 nucleotides, from about 500 nucleotides to about 4,400 nucleotides, from about 500 nucleotides to about 4,200 nucleotides, from about 500 nucleotides to about 4,000 nucleotides, from about 500 nucleotides to about 3,800 nucleotides, from about 500 nucleotides to about 3,600 nucleotides, from about 500 nucleotides to about 3.400 nucleotides, from about 500 nucleotides to about 3,200 nucleotides, from about 500 nucleotides to about 3,000 nucleotides, from about 500 nucleotides to about 2,800 nucleotides, from about 500 nucleotides to about 2,600 nucleotides, from about 500 nucleotides to about 2,400 nucleotides, from about 500 nucleotides to about 2,200 nucleotides, from about 500 nucleotides to about 2,000 nucleotides, from about 500 nucleotides to about 1,800 nucleotides, from about 500 nucleotides to about 1,600 nucleotides, from about 500 nucleotides to about 1,400 nucleotides, from about 500 nucleotides to about 1,200 nucleotides, from about 500 nucleotides to about 1,000 nucleotides, from about 500 nucleotides to about 800 nucleotides, from about 800 nucleotides to about 15,000 nucleotides, from about 800 nucleotides to about 14,500 nucleotides, from about 800 nucleotides to about 14.000 nucleotides, from about 800 nucleotides to about 13,500 nucleotides, from about 800 nucleotides to. Petition 870260061675, dated 06 / 23 / 2026, page 142 / 935 135 / 362 approximately 13,000 nucleotides, from approximately 800 nucleotides to approximately 12,500 nucleotides, from approximately 800 nucleotides to approximately 12,000 nucleotides, from approximately 800 nucleotides to approximately 11,500 nucleotides, from approximately 800 nucleotides to approximately 11,000 nucleotides, from approximately 800 nucleotides to approximately 10,500 nucleotides, from approximately 800 nucleotides to approximately 10,000 nucleotides, from approximately 800 nucleotides to approximately 9,500 nucleotides, from approximately 800 nucleotides to approximately 9,000 nucleotides, of from about 800 nucleotides to about 8,500 nucleotides, from about 800 nucleotides to about 8,000 nucleotides, from about 800 nucleotides to about 7,800 nucleotides, from about 800 nucleotides to about 7,600 nucleotides, from about 800 nucleotides to about 7,400 nucleotides, from about 800 nucleotides to about 7,200 nucleotides, from about 800 nucleotides to about 7,000 nucleotides, from about 800 nucleotides to about 6.800 nucleotides, from about 800 nucleotides to about 6,600 nucleotides, from about 800 nucleotides to about 6,400 nucleotides, from about 800 nucleotides to about 6,200 nucleotides, from about 800 nucleotides to about 6,000 nucleotides, from about 800 nucleotides to about 5,800 nucleotides, from about 800 nucleotides to about 5,600 nucleotides, from about 800 nucleotides to about 5,400 nucleotides, from about 800 nucleotides to about 5,200 nucleotides, from about 800 nucleotides to about 5,000 nucleotides, from about 800 nucleotides to about 4,800 nucleotides, from about 800 nucleotides to about 4,600 nucleotides, from about 800 nucleotides to about 4,400 nucleotides, from about 800 nucleotides to about 4,200 nucleotides, from about 800 nucleotides to about 4,000 nucleotides, from about 800 nucleotides to about 3,800 nucleotides, from about 800 nucleotides to about 3.600 nucleotides, from about 800 nucleotides to about 3,400 nucleotides. Petition 870260061675, dated 06 / 23 / 2026, page 143 / 935 136 / 362 approximately 800 nucleotides to approximately 3,200 nucleotides, of approximately 800 nucleotides to about 3,000 nucleotides, from about 800 nucleotides to about 2,800 nucleotides, from about 800 nucleotides to about 2,600 nucleotides, from about 800 nucleotides to about 2,400 nucleotides, from about 800 nucleotides to about 2,200 nucleotides, from about 800 nucleotides to about 2,000 nucleotides, from about 800 nucleotides to about 1,800 nucleotides, from about 800 nucleotides to about 1,600 nucleotides, from about 800 nucleotides to about 1,400 nucleotides, from about 800 nucleotides to about 1,200 nucleotides, from about 800 nucleotides to about 1,000 nucleotides, from about 1,000 nucleotides to about 15,000 nucleotides, from about 1,000 nucleotides to about 14,500 nucleotides, from about 1,000 nucleotides to about 14,000 nucleotides, from about 1,000 nucleotides to about 13,500 nucleotides, of approximately 1,000 nucleotides approximately 13,000 nucleotides, of approximately 1,000 nucleotides approximately 12,500 nucleotides, of approximately 1,000 nucleotides approximately 12,000 nucleotides, approximately 11,500 nucleotides, approximately 11,000 nucleotides, from approximately 1,000 nucleotides to approximately 1,000 nucleotides to approximately 1,000 nucleotides to approximately 10,500 nucleotides, from about 1,000 nucleotides to about 10,000 nucleotides, from about 1,000 nucleotides to about 9,000 nucleotides, from about 1,000 nucleotides to about 8,500 nucleotides, from about 1,000 nucleotides to about 8,000 nucleotides, from about 1,000 nucleotides to about 7,800 nucleotides, from about 1,000 nucleotides to about 7,600 nucleotides, from about 1,000 nucleotides to about 7,400 nucleotides, from about 1,000 nucleotides to about 7,200 nucleotides, from about 1,000 nucleotides to about 7,000 nucleotides, of from about 1,000 nucleotides to about 6,800 nucleotides, from about 1,000 nucleotides to about Petition 870260061675, dated 06 / 23 / 2026, page 144 / 935 137 / 362 of 6,600 nucleotides, from about 1,000 nucleotides to about 6,400 nucleotides, from about 1,000 nucleotides to about 6,200 nucleotides, from about 1,000 nucleotides to about 6,000 nucleotides, from about 1,000 nucleotides to about 5,800 nucleotides, from about 1,000 nucleotides to about 5,600 nucleotides, from about 1,000 nucleotides to about 5,400 nucleotides, from about 1,000 nucleotides to about 5,200 nucleotides, from about 1,000 nucleotides to about 5,000 nucleotides, from about 1,000 nucleotides to about 4,800 nucleotides, from about 1,000 nucleotides to about 4,600 nucleotides, from about 1,000 nucleotides to about 4,400 nucleotides, from about 1,000 nucleotides to about 4,200 nucleotides, from about 1,000 nucleotides to about 4,000 nucleotides, from about 1,000 nucleotides to about 3,800 nucleotides, from about 1,000 nucleotides to about 3,600 nucleotides, from about 1.from about 1,000 nucleotides to about 3,400 nucleotides, from about 1,000 nucleotides to about 3,200 nucleotides, from about 1,000 nucleotides to about 3,000 nucleotides, from about 1,000 nucleotides to about 2,600 nucleotides, from about 1,000 nucleotides to about 2,400 nucleotides, from about 1,000 nucleotides to about 2,200 nucleotides, from about 1,000 nucleotides to about 2,000 nucleotides, from about 1,000 nucleotides to about 1,800 nucleotides, from about 1,000 nucleotides to about 1,600 nucleotides, from about 1,000 nucleotides to about 1,400 nucleotides, from about 1,000 nucleotides to about 1,200 nucleotides, from about 1,200 nucleotides to about 15,000 nucleotides, from about 1,200 nucleotides to about 14,500 nucleotides, from about 1,200 nucleotides to about 14,000 nucleotides, from about 1,200 nucleotides to about 13,500 nucleotides, from about 1,200 nucleotides to about 13,000 nucleotides, from about 1.200 nucleotides to approximately 12,500 nucleotides, from approximately 1,200 nuclei. Petition 870260061675, dated 06 / 23 / 2026, p. 145 / 935 138 / 362 nucleotides to approximately 12,000 nucleotides, from approximately 1,200 nucleotides to approximately 11,500 nucleotides, from approximately 1,200 nucleotides to approximately 11,000 nucleotides, from approximately 1,200 nucleotides to approximately 10,500 nucleotides, from approximately 1,200 nucleotides to approximately 10,000 nucleotides, from approximately 1,200 nucleotides to approximately 9,500 nucleotides, from approximately 1,200 nucleotides to approximately 9,000 nucleotides, from approximately 1,200 nucleotides to approximately 8,500 nucleotides, from approximately 1,200 nucleotides to about 8,000 nucleotides, from about 1,200 nucleotides to about 7,800 nucleotides, from about 1,200 nucleotides to about 7,600 nucleotides, from about 1,200 nucleotides to about 7,400 nucleotides, from about 1,200 nucleotides to about 7,200 nucleotides, from about 1,200 nucleotides to about 7,000 nucleotides, from about 1,200 nucleotides to about 6,800 nucleotides, from about 1,200 nucleotides to about 6,600 nucleotides, from about 1.200 nucleotides to about 6,400 nucleotides, from about 1,200 nucleotides to about 6,200 nucleotides, from about 1,200 nucleotides to about 6,000 nucleotides, from about 1,200 nucleotides to about 5,800 nucleotides, from about 1,200 nucleotides to about 5,600 nucleotides, from about 1,200 nucleotides to about 5,400 nucleotides, from about 1,200 nucleotides to about 5,000 nucleotides, from about 1,200 nucleotides to about 4,800 nucleotides, from about 1,200 nucleotides to about 4,600 nucleotides, from about 1,200 nucleotides to about 4,400 nucleotides, from about 1,200 nucleotides to about 4,200 nucleotides, from about 1,200 nucleotides to about 4,000 nucleotides, from about 1,200 nucleotides to about 3,800 nucleotides, from about 1,200 nucleotides to about 3,600 nucleotides, from about 1,200 nucleotides to about 3,400 nucleotides, from about 1,200 nucleotides to about 3,200 nucleotides, from about 1.200 nucleotides to about 3,000 nucleotides, from about 1,200. Petition 870260061675, dated 06 / 23 / 2026, page 146 / 935 139 / 362 nucleotides to about 2,800 nucleotides, from about 1,200 nucleotides to about 2,600 nucleotides, from about 1,200 nucleotides to about 2,400 nucleotides, from about 1,200 nucleotides to about 2,200 nucleotides, from about 1,200 nucleotides to about 2,000 nucleotides, from about 1,200 nucleotides to about 1,800 nucleotides, from about 1,200 nucleotides to about 1,600 nucleotides, from about 1,200 nucleotides to about 1,400 nucleotides, from about 1,400 nucleotides to approximately 15,000 nucleotides, from approximately 1,400 nucleotides to approximately 14,500 nucleotides, from approximately 1,400 nucleotides to approximately 14,000 nucleotides, from approximately 1,400 nucleotides to approximately 13,500 nucleotides, from approximately 1,400 nucleotides to approximately 13,000 nucleotides, from approximately 1,400 nucleotides to approximately 12,500 nucleotides, from approximately 1,400 nucleotides to approximately 12,000 nucleotides, from approximately 1,400 nucleotides to approximately 11.500 nucleotides, from about 1,400 nucleotides to about 11,000 nucleotides, from about 1,400 nucleotides to about 10,500 nucleotides, from about 1,400 nucleotides to about 10,000 nucleotides, from about 1,400 nucleotides to about 9,500 nucleotides, from about 1,400 nucleotides to about 9,000 nucleotides, from about 1,400 nucleotides to about 8,500 nucleotides, from about 1,400 nucleotides to about 8,000 nucleotides, from about 1,400 nucleotides to about 7,800 nucleotides, of from approximately 1,400 nucleotides to approximately 7,600 nucleotides, from approximately 1,400 nucleotides to approximately 7,400 nucleotides, from approximately 1,400 nucleotides to approximately 7,200 nucleotides, from approximately 1,400 nucleotides to approximately 7,000 nucleotides, from approximately 1,400 nucleotides to approximately 6,800 nucleotides, from approximately 1,400 nucleotides to approximately 6,600 nucleotides, from approximately 1,400 nucleotides to approximately 6,400 nucleotides, from approximately 1,400 nucleotides to approximately 6.200 nucleotides, from about 1,400 nucleotides to about 6,000 nucleotides. Petition 870260061675, dated 06 / 23 / 2026, page 147 / 935 140 / 362 from about 1,400 nucleotides to about 5,800 nucleotides, from about 1,400 nucleotides to about 5,600 nucleotides, from about 1,400 nucleotides to about 5,400 nucleotides, from about 1,400 nucleotides to about 5,200 nucleotides, from about 1,400 nucleotides to about 5,000 nucleotides, from about 1,400 nucleotides to about 4,800 nucleotides, from about 1,400 nucleotides to about 4,600 nucleotides, from about 1,400 nucleotides to about 4,400 nucleotides, from about 1,400 nucleotides to about 4,200 nucleotides, from about 1,400 nucleotides to about 4,000 nucleotides, from about 1,400 nucleotides to about 3,800 nucleotides, from about 1,400 nucleotides to about 3,600 nucleotides, from about 1,400 nucleotides to about 3,400 nucleotides, from about 1,400 nucleotides to about 3,200 nucleotides, from about 1,400 nucleotides to about 3,000 nucleotides, from about 1,400 nucleotides to about 2.600 nucleotides, from about 1,400 nucleotides to about 2,400 nucleotides, from about 1,400 nucleotides to about 2,200 nucleotides, from about 1,400 nucleotides to about 2,000 nucleotides, from about 1,400 nucleotides to about 1,800 nucleotides, from about 1,400 nucleotides to about 1,600 nucleotides, from about 1,600 nucleotides to about 15,000 nucleotides, from about 1,600 nucleotides to about 14,500 nucleotides, from about 1,600 nucleotides to about 14,000 nucleotides, of from approximately 1,600 nucleotides to approximately 13,500 nucleotides, from approximately 1,600 nucleotides to approximately 13,000 nucleotides, from approximately 1,600 nucleotides to approximately 12,500 nucleotides, from approximately 1,600 nucleotides to approximately 12,000 nucleotides, from approximately 1,600 nucleotides to approximately 11,500 nucleotides, from approximately 1,600 nucleotides to approximately 11,000 nucleotides, from approximately 1,600 nucleotides to approximately 10,500 nucleotides, from approximately 1.600 nucleotides to about 10,000 nucleotides, from about 1,600 nucleotides to about. Petition 870260061675, dated 06 / 23 / 2026, page 148 / 935 141 / 362 9,500 nucleotides, from about 1,600 nucleotides to about 9,000 nucleotides, from about 1,600 nucleotides to about 8,500 nucleotides, from about 1,600 nucleotides to about 8,000 nucleotides, from about 1,600 nucleotides to about 7,800 nucleotides, from about 1,600 nucleotides to about 7,600 nucleotides, from about 1,600 nucleotides to about 7,400 nucleotides, from about 1,600 nucleotides to about 7,200 nucleotides, from about 1,600 nucleotides to about 7,000 nucleotides, from about from 1,600 nucleotides to about 6,800 nucleotides, from about 1,600 nucleotides to about 6,400 nucleotides, from about 1,600 nucleotides to about 6,200 nucleotides, from about 1,600 nucleotides to about 6,000 nucleotides, from about 1,600 nucleotides to about 5,800 nucleotides, from about 1,600 nucleotides to about 5,600 nucleotides, from about 1,600 nucleotides to about 5,400 nucleotides, from about 1,600 nucleotides to about 5.200 nucleotides, from about 1,600 nucleotides to about 5,000 nucleotides, from about 1,600 nucleotides to about 4,800 nucleotides, from about 1,600 nucleotides to about 4,600 nucleotides, from about 1,600 nucleotides to about 4,400 nucleotides, from about 1,600 nucleotides to about 4,200 nucleotides, from about 1,600 nucleotides to about 4,000 nucleotides, from about 1,600 nucleotides to about 3,800 nucleotides, from about 1,600 nucleotides to about 3,600 nucleotides, from about 1,600 nucleotides to about 3,400 nucleotides, from about 1,600 nucleotides to about 3,200 nucleotides, from about 1,600 nucleotides to about 3,000 nucleotides, from about 1,600 nucleotides to about 2,800 nucleotides, from about 1,600 nucleotides to about 2,600 nucleotides, from about 1,600 nucleotides to about 2,400 nucleotides, from about 1,600 nucleotides to about 2,200 nucleotides, from about 1,600 nucleotides to about 2.000 nucleotides, from about 1,600 nucleotides to about. Petition 870260061675, dated 06 / 23 / 2026, page 149 / 935 142 / 362 1,800 nucleotides, from about 1,800 nucleotides to about 15,000 nucleotides, from about 1,800 nucleotides to about 14,500 nucleotides, from about 1,800 nucleotides to about 14,000 nucleotides, from about 1,800 nucleotides to about 13,500 nucleotides, from about 1,800 nucleotides to about 13,000 nucleotides, from about 1,800 nucleotides to about 12,500 nucleotides, from about 1,800 nucleotides to about 12,000 nucleotides, from about 1,800 nucleotides to about 11,500 nucleotides, from about 1,800 nucleotides to about 11,000 nucleotides, from about 1,800 nucleotides to about 10,500 nucleotides, from about 1,800 nucleotides to about 10,000 nucleotides, from about 1,800 nucleotides to about 9,500 nucleotides, from about 1,800 nucleotides to about 9,000 nucleotides, from about 1,800 nucleotides to about 8,500 nucleotides, from about 1,800 nucleotides to about 8,000 nucleotides, from about 1.800 nucleotides to about 7,800 nucleotides, from about 1,800 nucleotides to about 7,600 nucleotides, from about 1,800 nucleotides to about 7,400 nucleotides, from about 1,800 nucleotides to about 7,200 nucleotides, from about 1,800 nucleotides to about 7,000 nucleotides, from about 1,800 nucleotides to about 6,800 nucleotides, from about 1,800 nucleotides to about 6,600 nucleotides, from about 1,800 nucleotides to about 6,400 nucleotides, from about 1,800 nucleotides to about 6,200 nucleotides, from about 1,800 nucleotides to about 6,000 nucleotides, from about 1,800 nucleotides to about 5,800 nucleotides, from about 1,800 nucleotides to about 5,600 nucleotides, from about 1,800 nucleotides to about 5,400 nucleotides, from about 1,800 nucleotides to about 5,200 nucleotides, from about 1,800 nucleotides to about 5,000 nucleotides, from about 1,800 nucleotides to about 4,800 nucleotides, from about 1.800 nucleotides to about 4,600 nucleotides, from about 1,800. Petition 870260061675, dated 06 / 23 / 2026, page 150 / 935 143 / 362 nucleotides to approximately 4,400 nucleotides, from approximately 1,800 nucleotides to approximately 4,200 nucleotides, from approximately 1,800 nucleotides to approximately 4,000 nucleotides, from approximately 1,800 nucleotides to approximately 3,800 nucleotides, from approximately 1,800 nucleotides to approximately 3,600 nucleotides, from approximately 1,800 nucleotides to approximately 3,400 nucleotides, from approximately 1,800 nucleotides to approximately 3,200 nucleotides, from approximately 1,800 nucleotides to approximately 3,000 nucleotides, from approximately 1,800 nucleotides from about 2,800 nucleotides, from about 1,800 nucleotides to about 2,600 nucleotides, from about 1,800 nucleotides to about 2,400 nucleotides, from about 1,800 nucleotides to about 2,200 nucleotides, from about 1,800 nucleotides to about 2,000 nucleotides, from about 2,000 nucleotides to about 15,000 nucleotides, from about 2,000 nucleotides to about 14,500 nucleotides, from about 2,000 nucleotides to about 14,000 nucleotides, 13,500 nucleotides, 13,000 nucleotides, 12,500 nucleotides, 12,000 nucleotides, 11,500 nucleotides, 11,000 nucleotides, from about 2,000 nucleotides to about from about 2,000 nucleotides to about from about 2,000 nucleotides to about from about 2,000 nucleotides to about from about 2,000 nucleotides to about from about 2,000 nucleotides to about from about 2,000 nucleotides to about from about 2,000 nucleotides to about 10,500 nucleotides, from about 2,000 nucleotides to about 10,000 nucleotides, from about 2,000 nucleotides to about 9,500 nucleotides, from about 2,000 nucleotides to about 9,000 nucleotides, from about 2,000 nucleotides to about 8,500 nucleotides, from about 2,000 nucleotides to about 8,000 nucleotides, from about 2,000 nucleotides to about 7,800 nucleotides, from about 2,000 nucleotides to about 7,600 nucleotides, from about 2,000 nucleotides to about 7,400 nucleotides, from about 2,000 nucleotides to about 7,200 nucleotides, of approximately 2,000 nucleotides Petition 870260061675, dated 06 / 23 / 2026, page 151 / 935 144 / 362 to about 7,000 nucleotides, from about 2,000 nucleotides to about 6,800 nucleotides, from about 2,000 nucleotides to about 6,600 nucleotides, from about 2,000 nucleotides to about 6,400 nucleotides, from about 2,000 nucleotides to about 6,200 nucleotides, from about 2,000 nucleotides to about 6,000 nucleotides, from about 2,000 nucleotides to about 5,800 nucleotides, from about 2,000 nucleotides to about 5,600 nucleotides, from about 2,000 nucleotides to about 5,400 nucleotides, from about 2,000 nucleotides to about 5,200 nucleotides, from about 2,000 nucleotides to about 5,000 nucleotides, from about 2,000 nucleotides to about 4,800 nucleotides, from about 2,000 nucleotides to about 4,600 nucleotides, from about 2,000 nucleotides to about 4,400 nucleotides, from about 2,000 nucleotides to about 4,200 nucleotides, from about 2,000 nucleotides to about 4,000 nucleotides, from about 2.from about 2,000 nucleotides to about 3,800 nucleotides, from about 2,000 nucleotides to about 3,600 nucleotides, from about 2,000 nucleotides to about 3,400 nucleotides, from about 2,000 nucleotides to about 3,200 nucleotides, from about 2,000 nucleotides to about 3,000 nucleotides, from about 2,000 nucleotides to about 2,800 nucleotides, from about 2,000 nucleotides to about 2,600 nucleotides, from about 2,000 nucleotides to about 2,400 nucleotides, from about 2,000 nucleotides to about 2,200 nucleotides, from about 2,200 nucleotides to about 15,000 nucleotides, from about 2,200 nucleotides to about 14,500 nucleotides, from about 2,200 nucleotides to about 14,000 nucleotides, from about 2,200 nucleotides to about 13,500 nucleotides, from about 2,200 nucleotides to about 13,000 nucleotides, from about 2,200 nucleotides to about 12,500 nucleotides, from about 2,200 nucleotides to about 12,000 nucleotides, from about 2.200 nucleotides to approximately 11,500 nucleotides, of approximately... Petition 870260061675, dated 06 / 23 / 2026, page 152 / 935 145 / 362 2,200 nucleotides to approximately 11,000 nucleotides, from approximately 2,200 nucleotides to approximately 10,500 nucleotides, from approximately 2,200 nucleotides to approximately 10,000 nucleotides, from approximately 9,500 nucleotides, from approximately 9,000 nucleotides, from approximately 8,500 nucleotides, from approximately 8,000 nucleotides, from approximately 7,800 nucleotides, from approximately 7,600 nucleotides, from approximately 7,400 nucleotides, from approximately 7,200 nucleotides, from approximately 7,000 nucleotides, from approximately 6,800 nucleotides, from approximately 6,600 nucleotides, of about 6,400 nucleotides, of about 6,200 nucleotides, of about 6,000 nucleotides, of about 5,800 nucleotides, of about 5,600 nucleotides, of about 5,400 nucleotides, of about 5,200 nucleotides, of about 5,000 nucleotides, of about 4,800 nucleotides, of about 4,600 nucleotides, of about 4,400 nucleotides, of about 4,200 nucleotides, of about 4,000 nucleotides, of about 3,800 nucleotides, of about 3.600 nucleotides, of approximately 3,400 nucleotides, of approximately 3,200 nucleotides, of approximately. 3,000 nucleotides, from about 2,800 nucleotides, from about 2,600 nucleotides, from about 2,400 nucleotides, from about 2,400 nucleotides to about 15,000 nucleotides, from about 2,400 nucleotides to about 14,500 nucleotides, from about 2,400 nucleotides to about 14,000 nucleotides, from about 2,400 nucleotides to about 13,500 nucleotides, from about 2,400 nucleotides to about 13,000 nucleotides, of approximately 2,400 nucleotides approximately 12,500 nucleotides, of approximately 2,400 nucleotides approximately 12,000 nucleotides, of approximately 2,400 nucleotides approximately 11,500 nucleotides, of approximately 2,400 nucleotides approximately 11,000 nucleotides, of approximately 2,400 nucleotides approximately 10,500 nucleotides, of approximately 2,400 nucleotides approximately 10,000 nucleotides, from about 2,400 nucleotides to about 9,500 nucleotides, from about 2,400 nucleotides to about 9,000 nucleotides Petition 870260061675, dated 06 / 23 / 2026, page 153 / 935 146 / 362 nucleotides, from about 2,400 nucleotides to about 8,500 nucleotides, from about 2,400 nucleotides to about 8,000 nucleotides, from about 2,400 nucleotides to about 7,800 nucleotides, from about 2,400 nucleotides to about 7,600 nucleotides, from about 2,400 nucleotides to about 7,400 nucleotides, from about 2,400 nucleotides to about 7,200 nucleotides, from about 2,400 nucleotides to about 7,000 nucleotides, from about 2,400 nucleotides to about 6,800 nucleotides, from about from 2,400 nucleotides to about 6,600 nucleotides, from about 2,400 nucleotides to about 6,400 nucleotides, from about 2,400 nucleotides to about 6,200 nucleotides, from about 2,400 nucleotides to about 6,000 nucleotides, from about 2,400 nucleotides to about 5,800 nucleotides, from about 2,400 nucleotides to about 5,600 nucleotides, from about 2,400 nucleotides to about 5,400 nucleotides, from about 2,400 nucleotides to about 5.200 nucleotides, from about 2,400 nucleotides to about 5,000 nucleotides, from about 2,400 nucleotides to about 4,800 nucleotides, from about 2,400 nucleotides to about 4,600 nucleotides, from about 2,400 nucleotides to about 4,400 nucleotides, from about 2,400 nucleotides to about 4,200 nucleotides, from about 2,400 nucleotides to about 4,000 nucleotides, from about 2,400 nucleotides to about 3,800 nucleotides, from about 2,400 nucleotides to about 3,600 nucleotides, from about 2,400 nucleotides to about 3,400 nucleotides, from about 2,400 nucleotides to about 3,200 nucleotides, from about 2,400 nucleotides to about 3,000 nucleotides, from about 2,400 nucleotides to about 2,800 nucleotides, from about 2,400 nucleotides to about 2,600 nucleotides, from about 2,600 nucleotides to about 15,000 nucleotides, from about 2,600 nucleotides to about 14,500 nucleotides, from about 2,600 nucleotides to about. 14,000 nucleotides, from about 2,600 nucleotides to about Petition 870260061675, dated 06 / 23 / 2026, page 154 / 935 147 / 362 13,500 nucleotides, of approximately 2,600 nucleotides approximately 13,000 nucleotides, of approximately 2,600 nucleotides approximately 12,500 nucleotides, of approximately 2,600 nucleotides approximately 12,000 nucleotides, of approximately 2,600 nucleotides approximately 11,500 nucleotides, of approximately 2,600 nucleotides approximately 11,000 nucleotides, of approximately 2,600 nucleotides approximately 10,500 nucleotides, of approximately 2,600 nucleotides approximately 10,000 nucleotides, from about 2,600 nucleotides to about 9,500 nucleotides, from about 2,600 nucleotides to about 9,000 nucleotides, from about 2,600 nucleotides to about 8,500 nucleotides, from about 2,600 nucleotides to about 8,000 nucleotides, from about 2,600 nucleotides to about 7,800 nucleotides, from about 2,600 nucleotides to about 7,600 nucleotides, from about 2,600 nucleotides to about 7,400 nucleotides, from about 2,600 nucleotides to about 7,200 nucleotides, from about 2,600 nucleotides to about 7,000 nucleotides, from about 2,600 nucleotides to about 6,800 nucleotides, from about 2,600 nucleotides to about 6,600 nucleotides, from about 2,600 nucleotides to about 6,400 nucleotides, from about 2,600 nucleotides to about 6,200 nucleotides, from about 2,600 nucleotides to about 6,000 nucleotides, from about 2,600 nucleotides to about 5,800 nucleotides, from about 2,600 nucleotides to about 5.600 nucleotides, from about 2,600 nucleotides to about 5,400 nucleotides, from about 2,600 nucleotides to about 5,200 nucleotides, from about 2,600 nucleotides to about 5,000 nucleotides, from about 2,600 nucleotides to about 4,800 nucleotides, from about 2,600 nucleotides to about 4,600 nucleotides, from about 2,600 nucleotides to about 4,400 nucleotides, from about 2,600 nucleotides to about 4,200 nucleotides, from about 2,600 nucleotides to about 4,000 nucleotides, from about 2,600 nucleotides to approximately 3,800 nucleotides. Petition 870260061675, dated 06 / 23 / 2026, page 155 / 935 148 / 362 from about 2,600 nucleotides to about 3,600 nucleotides, from about 2,600 nucleotides to about 3,400 nucleotides, from about 2,600 nucleotides to about 3,200 nucleotides, from about 2,600 nucleotides to about 3,000 nucleotides, from about 2,600 nucleotides to about 2,800 nucleotides, from about 2,800 nucleotides to about 15,000 nucleotides, from about 2,800 nucleotides to about 14,500 nucleotides, from about 2,800 nucleotides to about 14,000 13,500 13,000 12,500 12,000 11,500 11,000 10,500 nucleotides, from about 2,800 nucleotides to about nucleotides, from about 2,800 nucleotides to about nucleotides, from about 2,800 nucleotides to about nucleotides, from about 2,800 nucleotides to about nucleotides, from about 2,800 nucleotides to about nucleotides, from about 2,800 nucleotides to about nucleotides, from about 2,800 nucleotides to about nucleotides, from about 2,800 nucleotides to about nucleotides, from about 2,800 nucleotides to about nucleotides 10,000 nucleotides, from about 2,800 nucleotides to about 9,500 nucleotides, from about 2,800 nucleotides to about 9,000 nucleotides, from about 2,800 nucleotides to about 8,500 nucleotides, from about 2,800 nucleotides to about 8,000 nucleotides, from about 2,800 nucleotides to about 7,800 nucleotides, from about 2,800 nucleotides to about 7,600 nucleotides, from about 2,800 nucleotides to about 7,400 nucleotides, from about 2,800 nucleotides to about 7,200 nucleotides, of from approximately 2,800 nucleotides to approximately 7,000 nucleotides, from approximately 2,800 nucleotides to approximately 6,800 nucleotides, from approximately 2,800 nucleotides to approximately 6,600 nucleotides, from approximately 2,800 nucleotides to approximately 6,400 nucleotides, from approximately 2,800 nucleotides to approximately 6,200 nucleotides, from approximately 2,800 nucleotides to approximately 6,000 nucleotides, from approximately 2,800 nucleotides to approximately 5,800 nucleotides, from approximately 2,800 nucleotides to approximately 5.600 nucleotides, approximately. Petition 870260061675, dated 06 / 23 / 2026, page 156 / 935 149 / 362 2,800 nucleotides to about 5,400 nucleotides, from about 2,800 nucleotides to about 5,200 nucleotides, from about 2,800 nucleotides to about 5,000 nucleotides, from about 2,800 nucleotides to about 4,800 nucleotides, from about 2,800 nucleotides to about 4,600 nucleotides, from about 2,800 nucleotides to about 4,400 nucleotides, from about 2,800 nucleotides to about 4,200 nucleotides, from about 2,800 nucleotides to about 4,000 nucleotides, from about 2,800 nucleotides to about 3,800 nucleotides, from about 2,800 nucleotides to about 3,600 nucleotides, from about 2,800 nucleotides to about 3,400 nucleotides, from about 2,800 nucleotides to about 3,200 nucleotides, from about 2,800 nucleotides to about 3,000 nucleotides, from about 3,000 nucleotides to about 15,000 nucleotides, from about 3,000 nucleotides to about 14,500 nucleotides, from about 3,000 nucleotides to about 14,000 nucleotides, from about 3,000 nucleotides to about 13,500 nucleotides, 13,000 nucleotides, 12,500 nucleotides, 12,000 nucleotides, 11,500 nucleotides, 11,000 nucleotides, from about 3,000 nucleotides to about from about 3,000 nucleotides to about from about 3,000 nucleotides to about from about 3,000 nucleotides to about from about 3,000 nucleotides to about from about 3,000 nucleotides to about from about 3,000 nucleotides to about 10,500 nucleotides, from about 3,000 nucleotides to about 10,000 nucleotides, from about 3,000 nucleotides to about 9,500 nucleotides, from about 3,000 nucleotides to about 9,000 nucleotides, from about 3,000 nucleotides to about 8,500 nucleotides, from about 3,000 nucleotides to about 8,000 nucleotides, from about 3,000 nucleotides to about 7,800 nucleotides, from about 3,000 nucleotides to about 7,600 nucleotides, from about 3,000 nucleotides to about 7,400 nucleotides, from about 3,000 nucleotides to about 7,200 nucleotides, of approximately 3,000 nucleotides Petition 870260061675, dated 06 / 23 / 2026, page 157 / 935 150 / 362 to approximately 7,000 nucleotides, from approximately 3,000 nucleotides to approximately 6,800 nucleotides, from approximately 3,000 nucleotides to approximately 6,600 nucleotides, from approximately 3,000 nucleotides to approximately 6,400 nucleotides, from approximately 3,000 nucleotides to approximately 6,200 nucleotides, from approximately 3,000 nucleotides to approximately 6,000 nucleotides, from approximately 3,000 nucleotides to approximately 5,800 nucleotides, from approximately 3,000 nucleotides to approximately 5,600 nucleotides, from approximately 3,000 nucleotides to approximately 5,400 nucleotides, from about 3,000 nucleotides to about 5,200 nucleotides, from about 3,000 nucleotides to about 5,000 nucleotides, from about 3,000 nucleotides to about 4,800 nucleotides, from about 3,000 nucleotides to about 4,600 nucleotides, from about 3,000 nucleotides to about 4,400 nucleotides, from about 3,000 nucleotides to about 4,200 nucleotides, from about 3,000 nucleotides to about 4,000 nucleotides, from about 3.from approximately 3,800 nucleotides, from approximately 3,000 nucleotides to approximately 3,600 nucleotides, from approximately 3,000 nucleotides to approximately 3,400 nucleotides, from approximately. 3,000 nucleotides to about 3,200 nucleotides, from about 3,200 nucleotides to about 15,000 nucleotides, from about 3,200 nucleotides to about 14,500 nucleotides, from about 3,200 nucleotides to about 14,000 nucleotides, from about 3,200 nucleotides to about 13,500 nucleotides, from about 3,200 nucleotides to about 13,000 nucleotides, from about 3,200 nucleotides to about 12,500 nucleotides, of approximately 3,200 nucleotides approximately 12,000 nucleotides, of approximately 3,200 nucleotides approximately 11,500 nucleotides, of approximately 3,200 nucleotides approximately 11,000 nucleotides, of approximately 3,200 nucleotides approximately 10,500 nucleotides, of approximately 3,200 nucleotides approximately 10,000 nucleotides, from about 3,200 nucleotides to about 9,500 nucleotides, from about 3,200 nucleotides to about 9,000 nucleotides Petition 870260061675, dated 06 / 23 / 2026, page 158 / 935 151 / 362 nucleotides, from about 3,200 nucleotides to about 8,500 nucleotides, from about 3,200 nucleotides to about 8,000 nucleotides, from about 3,200 nucleotides to about 7,800 nucleotides, from about 3,200 nucleotides to about 7,600 nucleotides, from about 3,200 nucleotides to about 7,400 nucleotides, from about 3,200 nucleotides to about 7,200 nucleotides, from about 3,200 nucleotides to about 7,000 nucleotides, from about 3,200 nucleotides to about 6,800 nucleotides, from about from 3,200 nucleotides to about 6,600 nucleotides, from about 3,200 nucleotides to about 6,400 nucleotides, from about 3,200 nucleotides to about 6,200 nucleotides, from about 3,200 nucleotides to about 6,000 nucleotides, from about 3,200 nucleotides to about 5,800 nucleotides, from about 3,200 nucleotides to about 5,600 nucleotides, from about 3,200 nucleotides to about 5,400 nucleotides, from about 3,200 nucleotides to about 5.200 nucleotides, from about 3,200 nucleotides to about 5,000 nucleotides, from about 3,200 nucleotides to about 4,800 nucleotides, from about 3,200 nucleotides to about 4,600 nucleotides, from about 3,200 nucleotides to about 4,400 nucleotides, from about 3,200 nucleotides to about 4,200 nucleotides, from about 3,200 nucleotides to about 4,000 nucleotides, from about 3,200 nucleotides to about 3,800 nucleotides, from about 3,200 nucleotides to about 3,600 nucleotides, from about 3,200 nucleotides to about 3,400 nucleotides, from about 3,400 nucleotides to about 15,000 nucleotides, from about 3,400 nucleotides to about 14,500 nucleotides, from about 3,400 nucleotides to about 14,000 nucleotides, from about 3,400 nucleotides to about 13,500 nucleotides, from about 3,400 nucleotides to about 13,000 nucleotides, from about 3,400 nucleotides to about 12,500 nucleotides, from about 3,400 nucleotides to about 12.000 nucleotides, from about 3,400 nucleotides to about. Petition 870260061675, dated 06 / 23 / 2026, page 159 / 935 152 / 362 11,500 nucleotides, approximately 11,000 nucleotides, approximately 10,500 nucleotides, approximately 3,400 nucleotides approximately 3,400 nucleotides approximately 3,400 nucleotides approximately 10,000 nucleotides, from about 3,400 nucleotides to about 9,500 nucleotides, from about 3,400 nucleotides to about 9,000 nucleotides, from about 3,400 nucleotides to about 8,500 nucleotides, from about 3,400 nucleotides to about 8,000 nucleotides, from about 3,400 nucleotides to about 7,800 nucleotides, from about 3,400 nucleotides to about 7,600 nucleotides, from about 3,400 nucleotides to about 7,400 nucleotides, from about 3,400 nucleotides to about 7,200 nucleotides, of from approximately 3,400 nucleotides to approximately 7,000 nucleotides, from approximately 3,400 nucleotides to approximately 6,800 nucleotides, from approximately 3,400 nucleotides to approximately 6,600 nucleotides, from approximately 3,400 nucleotides to approximately 6,400 nucleotides, from approximately 3,400 nucleotides to approximately 6,200 nucleotides, from approximately 3,400 nucleotides to approximately 6,000 nucleotides, from approximately 3,400 nucleotides to approximately 5,800 nucleotides, from approximately 3,400 nucleotides to approximately 5.600 nucleotides, from about 3,400 nucleotides to about 5,400 nucleotides, from about 3,400 nucleotides to about 5,200 nucleotides, from about 3,400 nucleotides to about 5,000 nucleotides, from about 3,400 nucleotides to about 4,800 nucleotides, from about 3,400 nucleotides to about 4,600 nucleotides, from about 3,400 nucleotides to about 4,400 nucleotides, from about 3,400 nucleotides to about 4,200 nucleotides, from about 3,400 nucleotides to about 4,000 nucleotides, from about 3,400 nucleotides to about 3,800 nucleotides, from about 3,400 nucleotides to about 3,600 nucleotides, from about 3,600 nucleotides to about 15,000 nucleotides, from about 3,600 nucleotides to about 14,500 nucleotides, from about 3,600 nucleotides to about 14,000 nucleotides, from about 3,600 nu. Petition 870260061675, dated 06 / 23 / 2026, page 160 / 935 153 / 362 nucleotides to approximately 13,500 nucleotides, from approximately 3,600 nucleotides to approximately 13,000 nucleotides, from approximately 3,600 nucleotides to approximately 12,500 nucleotides, from approximately 3,600 nucleotides to approximately 12,000 nucleotides, from approximately 11,500 nucleotides, from approximately 11,000 nucleotides, approximately 10,500 nucleotides, from approximately 3,600 nucleotides to approximately 3,600 nucleotides approximately 3,600 nucleotides approximately 3,600 nucleotides approximately 10,000 nucleotides, from about 3,600 nucleotides to about 9,500 nucleotides, from about 3,600 nucleotides to about 9,000 nucleotides, from about 3,600 nucleotides to about 8,500 nucleotides, from about 3,600 nucleotides to about 8,000 nucleotides, from about 3,600 nucleotides to about 7,800 nucleotides, from about 3,600 nucleotides to about 7,600 nucleotides, from about 3,600 nucleotides to about 7,400 nucleotides, from about 3,600 nucleotides to about 7,200 nucleotides, of from approximately 3,600 nucleotides to approximately 7,000 nucleotides, from approximately 3,600 nucleotides to approximately 6,800 nucleotides, from approximately 3,600 nucleotides to approximately 6,600 nucleotides, from approximately 3,600 nucleotides to approximately 6,400 nucleotides, from approximately 3,600 nucleotides to approximately 6,200 nucleotides, from approximately 3,600 nucleotides to approximately 6,000 nucleotides, from approximately 3,600 nucleotides to approximately 5,800 nucleotides, from approximately 3,600 nucleotides to approximately 5.600 nucleotides, from about 3,600 nucleotides to about 5,400 nucleotides, from about 3,600 nucleotides to about 5,200 nucleotides, from about 3,600 nucleotides to about 5,000 nucleotides, from about 3,600 nucleotides to about 4,800 nucleotides, from about 3,600 nucleotides to about 4,600 nucleotides, from about 3,600 nucleotides to about 4,400 nucleotides, from about 3,600 nucleotides to about 4,200 nucleotides, from about 3,600 nucleotides to about 4,000 nucleotides, from about 3,600 nucleotides to approximately 3,800 nucleotides. Petition 870260061675, dated 06 / 23 / 2026, page 161 / 935 154 / 362 from about 3,800 nucleotides to about 15,000 nucleotides, from about 3,800 nucleotides to about 14,500 nucleotides, from about 3,800 nucleotides to about 14,000 nucleotides, from about 3,800 nucleotides to about 13,500 nucleotides, from about 3,800 nucleotides to about 13,000 nucleotides, from about 3,800 nucleotides to about 12,500 nucleotides, from about 3,800 nucleotides to about 12,000 nucleotides, from about 3,800 nucleotides to about 11,500 nucleotides, from about 3,800 nucleotides to about 11,000 nucleotides, from about 3,800 nucleotides to about 10,500 nucleotides, from about 3,800 nucleotides to about 10,000 nucleotides, from about 3,800 nucleotides to about 9,500 nucleotides, from about 3,800 nucleotides to about 9,000 nucleotides, from about 3,800 nucleotides to about 8,500 nucleotides, from about 3,800 nucleotides to about 8,000 nucleotides, from about 3,800 nucleotides to about 7.800 nucleotides, from about 3,800 nucleotides to about 7,600 nucleotides, from about 3,800 nucleotides to about 7,400 nucleotides, from about 3,800 nucleotides to about 7,200 nucleotides, from about 3,800 nucleotides to about 7,000 nucleotides, from about 3,800 nucleotides to about 6,800 nucleotides, from about 3,800 nucleotides to about 6,600 nucleotides, from about 3,800 nucleotides to about 6,400 nucleotides, from about 3,800 nucleotides to about 6,200 nucleotides, from about 3,800 nucleotides to about 6,000 nucleotides, from about 3,800 nucleotides to about 5,800 nucleotides, from about 3,800 nucleotides to about 5,600 nucleotides, from about 3,800 nucleotides to about 5,400 nucleotides, from about 3,800 nucleotides to about 5,200 nucleotides, from about 3,800 nucleotides to about 5,000 nucleotides, from about 3,800 nucleotides to about 4,800 nucleotides, from about 3,800 nucleotides to about 4.600 nucleotides, from about 3,800 nucleotides to about. Petition 870260061675, dated 06 / 23 / 2026, page 162 / 935 155 / 362 4,200 nucleotides, from about 3,800 nucleotides to about 4,000 nucleotides, from about 4,000 nucleotides to about 15,000 nucleotides, from about 4,000 nucleotides to about 14,500 nucleotides, from about 4,000 nucleotides to about 14,000 nucleotides, from about 4,000 nucleotides to about 13,500 nucleotides, from about 4,000 nucleotides to about 13,000 nucleotides, from about 4,000 nucleotides to about 12,500 nucleotides, from about 4,000 nucleotides to about 12,000 nucleotides, from about 4,000 nucleotides to about 11,500 nucleotides, from about 4,000 nucleotides to about 11,000 nucleotides, from about 4,000 nucleotides to about 10,500 nucleotides, from about 4,000 nucleotides to about 10,000 nucleotides, from about 4,000 nucleotides to about 9,500 nucleotides, from about 4,000 nucleotides to about 9,000 nucleotides, from about 4,000 nucleotides to about 8,500 nucleotides, from about 4.from about 4,000 nucleotides to about 8,000 nucleotides, from about 4,000 nucleotides to about 7,800 nucleotides, from about 4,000 nucleotides to about 7,600 nucleotides, from about 4,000 nucleotides to about 7,400 nucleotides, from about 4,000 nucleotides to about 7,200 nucleotides, from about 4,000 nucleotides to about 7,000 nucleotides, from about 4,000 nucleotides to about 6,800 nucleotides, from about 4,000 nucleotides to about 6,600 nucleotides, from about 4,000 nucleotides to about 6,400 nucleotides, from about 4,000 nucleotides to about 6,200 nucleotides, from about 4,000 nucleotides to about 6,000 nucleotides, from about 4,000 nucleotides to about 5,800 nucleotides, from about 4,000 nucleotides to about 5,600 nucleotides, from about 4,000 nucleotides to about 5,400 nucleotides, from about 4,000 nucleotides to about 5,200 nucleotides, f...

Claims

1. Invention, characterized by the fact that it is in any form of its embodiments or in any category of claim that may be claimed, for example, a product, or process, or use encompassed by the object initially described, disclosed, or illustrated in the patent application, Composition, comprising an adeno-associated virus (AAV) nucleic acid vector, wherein the AAV nucleic acid vector comprises a 5' inverted terminal repeat (ITR); a cytomegalovirus (CMV) enhancer; a chicken β-actin (CBA) promoter; a chimeric intron comprising the nucleic acid sequence according to SEQ ID NO: 16; a 5' untranslated region (UTR); a coding sequence encoding a CLRN1 protein isoform, wherein the CLRN1 protein isoform comprises the amino acid sequence of SEQ ID NO: 3; a 3' UTR; a polyadenylation signal; and a 3' ITR;and / or Composition, according to any of the above claims, further comprising one or more features: a) a capsid; b) an AAV capsid; and / or c) an Anc80 capsid; and / or Kit, comprising a composition, as defined in any of the above claims; and / or Petition 870260061675, dated 06 / 23 / 2026, p. 371 / 935; 2 / 9 Kit according to the above claim, further comprising a pre-filled syringe or vial, wherein the pre-filled syringe or vial comprises the composition; and / or Kit according to the above claim, wherein the composition is formulated as an aqueous composition, a solid composition or a lyophilized composition; and / or Kit according to the above claim, further comprising a liquid; and / or Kit according to any of the above claims, further comprising instructions for performing a method; and / or Use of a composition as defined in any of the above claims, in the preparation of a pharmaceutical composition or kit for increasing the expression of a complete CLRN1 protein in a mammalian cell and / or eye and / or for the treatment of hearing loss, vision loss or both in a human individual;and / or Use of a composition as defined in any of the above claims, in the preparation of a medicament to increase the expression of a complete CLRN1 protein in a mammalian cell and / or eye and / or for the treatment of hearing loss, vision loss, Usher syndrome type III, retinitis pigmentosa or a combination thereof in a human individual; and / or Composition, comprising a unique nucleic acid vector, wherein the vector comprises a first coding sequence encoding a first isoform of the CLRN1 protein, wherein the first coding sequence comprises a nucleotide sequence spanning two consecutive exons of a CLRN1 genomic DNA and lacking an intronic sequence between the two consecutive introns; and / or Petition 870260061675, dated 06 / 23 / 2026, pp. 372 / 935; 3 / 9 Composition, according to the above claim, wherein the first isoform of the CLRN1 protein comprises a sequence that is at least 95% identical to SEQ ID No. 3; and / or Composition, according to any of the above claims, wherein the single nucleic acid vector further comprises a 5' untranslated region (UTR), a 3' UTR or both, optionally wherein the 5' UTR comprises at least 10, or at least 20 contiguous nucleotides of SEQ ID No. 12; and / or the 3' UTR comprises at least 10, or at least 20 contiguous nucleotides of SEQ ID No. 36; and / or Composition, according to any of the above claims, wherein the single nucleic acid vector is: (i) a plasmid; (ii) a transposon; (iii) a cosmid; (iv) an artificial chromosome, optionally selected from a human artificial chromosome (HAC), yeast artificial chromosome (YAC), bacterial artificial chromosome (BAC) or a P1-derived artificial chromosome (PAC);or (v) a viral vector, optionally selected from an adeno-associated virus (AAV) vector, an adenoviral vector, a lentiviral vector or a retroviral vector, preferably an AAV vector; and / or Composition, according to any of the above claims, wherein the single nucleic acid vector further comprises one or both of a promoter and a Kozak sequence, optionally wherein the promoter is an inducible promoter, a constitutive promoter or a tissue-specific promoter; and / or Composition, according to any of the above claims Petition 870260061675, dated 06 / 23 / 2026, pp. 373 / 935; 4 / 9 Compositions, wherein the single nucleic acid vector further comprises a polyadenylation signal sequence; and / or Composition, according to any of the above claims, wherein it further comprises a pharmaceutically acceptable excipient; and / or Kit, comprising a composition, as defined in any of claims 1 to 7; and / or Composition according to any of the above claims, or the kit according to any of the above claims, which is for use, comprising the introduction, into the cochlea of ​​a mammal, of a therapeutically effective amount of the composition; and / or Composition or kit for use, according to any of the above claims, wherein the mammal is a human; and / or has been previously identified as having a defective CLRN1 gene;and / or Composition according to any of the above claims, or the kit according to any of the above claims, which is for use in increasing the expression of a complete CLRN1 protein in a mammalian cell, comprising introducing the composition into the mammalian cell; and / or Composition according to any of the above claims, or the kit according to any of the above claims, which is for use in increasing the expression of a complete CLRN1 protein in an inner hair cell, an outer hair cell, or both, in the cochlea of ​​a mammal, comprising introducing into the mammalian cochlea a therapeutically effective amount of the composition; and / or Composition according to any of the above claims Petition 870260061675, dated 06 / 23 / 2026, p. 374 / 935; 5 / 9 of the above claims, or the kit according to any of the above claims, which is for use in increasing the expression of a complete CLRN1 protein in a mammalian eye, comprising intraocular administration into the mammalian eye of a therapeutically effective amount of the composition; and / or Composition according to any of the above claims, or the kit according to any of the above claims, which is for use in treating hearing loss in an individual identified as having a defective CLRN1 gene, comprising administering a therapeutically effective amount of the composition into the individual's cochlea;and / or Composition according to any of the above claims, or kit according to any of the above claims, which is for use in the treatment of vision loss in an individual identified as having a defective CLRN1 gene, comprising administering a therapeutically effective amount of the composition into the individual's eye; and / or Use of a single nucleic acid vector of the composition as defined in any of the above claims, which is in the preparation of a pharmaceutical composition or kit to increase the expression of a complete CLRN1 protein in a mammalian cell and / or eye and / or for the treatment of hearing loss, vision loss or both in a human individual;and / or Composition, comprising at least two different nucleic acid vectors, wherein: each of the at least two different vectors comprises a coding sequence that encodes a different portion of a CLRN1 protein, each of the coded portions having at least 30 amino acid residues in length, wherein the Petition 870260061675, dated 06 / 23 / 2026, page 375 / 935; 6 / 9 The amino acid sequence of each of the encoded portions may optionally partially overlap with the amino acid sequence of one of the different encoded portions; no single vector of the at least two different vectors encodes a complete CLRN1 protein; at least one of the coding sequences comprises a nucleotide sequence spanning two consecutive exons of the CLRN1 genomic DNA and does not have an intronic sequence between the two consecutive exons; and when introduced into a mammalian cell, the at least two different vectors undergo homologous recombination with each other, thus forming a recombined nucleic acid that encodes a complete CLRN1 protein;and / or Composition, comprising a single nucleic acid vector, wherein the vector comprises one or both of (i) a first coding sequence encoding a first isoform of the CLRN1 protein, and (ii) a second coding sequence encoding a second isoform of the CLRN1 protein, wherein one or both of the first and second coding sequences comprise a nucleotide sequence spanning two consecutive exons of a CLRN1 genomic DNA and do not have an intronic sequence between the two consecutive introns; Composition, comprising two different nucleic acid vectors, wherein: a first nucleic acid vector of the two different nucleic acid vectors comprises a promoter, a first coding sequence encoding an N-terminal portion of a CLRN1 protein positioned 3' from the promoter, and a splicing donor sequence positioned at the 3' end of the first coding sequence; and Petition 870260061675, dated 06 / 23 / 2026, p. 376 / 935;7 / 9 a second nucleic acid vector of the two different nucleic acid vectors comprises a splicing acceptor sequence, a second coding sequence encoding a C-terminal portion of a CLRN1 protein positioned at the 3' end of the splicing acceptor sequence, and a polyadenylation signal sequence at the 3' end of the second coding sequence; wherein each of the coding portions is at least 30 amino acid residues in length, wherein the amino acid sequences of the two coding portions do not overlap, wherein no single vector of the two different vectors encodes a complete CLRN1 protein; and when introduced into a mammalian cell, splicing occurs between the splicing donor sequence and the splicing acceptor sequence, thereby forming a recombined nucleic acid encoding a complete CLRN1 protein;and / or Composition, comprising two different nucleic acid vectors, wherein: a first nucleic acid vector of the two different nucleic acid vectors comprises a promoter, a first coding sequence encoding an N-terminal portion of a CLRN1 protein positioned 3' from the promoter, a splicing donor sequence positioned at the 3' end of the first coding sequence and a first detectable marker gene positioned 3' from the splicing donor signal sequence; and a second nucleic acid vector of the two different nucleic acid vectors comprises a second detectable marker gene, a splicing acceptor sequence positioned 3' from the second detectable marker gene, a second coding sequence encoding a C-terminal portion of a CLRN1 protein positioned at the 3' end of the splicing acceptor sequence and a Petition 870260061675, dated 06 / 23 / 2026, page 377 / 935; 8 / 9 polyadenylation signal sequence positioned at the 3' end of the second coding sequence; wherein each of the coding portions is at least 30 amino acid residues in length, wherein the amino acid sequences of the coding portions do not overlap, wherein no single vector of the two different vectors encodes a complete CLRN1 protein; and when introduced into a mammalian cell, splicing occurs between the splicing donor sequence and the splicing acceptor sequence, thus forming a recombined nucleic acid that encodes a complete CLRN1 protein;and / or Composition, comprising two different nucleic acid vectors, wherein: a first nucleic acid vector of the two different nucleic acid vectors comprises a promoter, a first coding sequence encoding an N-terminal portion of a CLRN1 protein positioned 3' from the promoter, a splicing donor sequence positioned at the 3' end of the first coding sequence, and a recombinogenic region of phage F1 positioned 3' relative to the splicing donor signal sequence;and a second nucleic acid vector of the two different nucleic acid vectors comprises a recombinogenic region of phage F1, a splicing acceptor sequence positioned 3' from the second recombinogenic region of phage F1, a second coding sequence encoding a C-terminal portion of a CLRN1 protein positioned at the 3' end of the splicing acceptor sequence, and a polyadenylation signal sequence positioned at the 3' end of the second coding sequence; wherein each of the two coding portions is at least 30 amino acid residues in length, wherein the Petition 870260061675, dated 06 / 23 / 2026, page 378 / 935; 9 / 9 amino acid sequences of the two encoded portions do not overlap, wherein no single vector of the two different vectors encodes a complete CLRN1 protein; and when introduced into a mammalian cell, splicing occurs between the splicing donor sequence and the splicing acceptor sequence, thus forming a recombined nucleic acid that encodes a complete CLRN1 protein; and / or Kit, comprising any of the compositions as defined in any of the above claims; and / or Use of a single nucleic acid vector and / or any of the foregoing compositions in the preparation of a pharmaceutical composition or kit for the treatment of a condition or disease in a human individual.

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