Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of Application/Election/Restrictions
Applicant’s election of Group I (claims 1-2, 12-14, 16, 19, 23, 26 and 30) and SEQ ID NOs: 16-18 and SEQ ID NOs: 19-21 for CDR-H1-3 and CDR-L1-3; sequence set for VH and VL recited claim 2 b) (i.e. SEQ ID NO:100 or at least 80%~95% identity to SEQ ID NO:100 for VH and/or SEQ ID NO: 101 or at least 80%~95% identity to SEQ ID NO:101; a conservatively substituted sequence thereof; or a nucleotide sequence set out in SEQ ID NO:78 for VH and/or a nucleotide sequence set out in SEQ ID NO:79 for VL or a codon degenerate or optimized version thereof); SEQ ID NO:182 for linker; SEQ ID NO:174 for targeting moiety linker; SEQ ID NO:258 for nucleic acid sequence in the reply filed on August 28, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 3-11, 15, 17-18, 20-22, 24-25, 27-29 and 31-47 are canceled. Claims 1-2, 12-14, 16, 19, 23, 26 and 30 are pending in this application. Election was treated as without traverse in the reply filed on August 28, 2025.
Claims 1-2, 12-14, 16, 19, 23, 26 and 30 are under examination with respect to SEQ ID NOs: 16-18 and SEQ ID NOs: 19-21 for CDR-H1-3 and CDR-L1-3, sequence set recited claim 2 b) for VH and SEQ ID NO:VL, SEQ ID NO:182 for linker, SEQ ID NO:174 for targeting moiety linker, SEQ ID NO:258 for nucleic acid sequence in this office action.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because of the following informalities: The use of the term “nanobody” ([0019]), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Appropriate correction is required.
Claim Objections
Claims 2 and 19 are objected to because of the following informalities:
i. Claim 2 recites “b)……and/or wherein the antibody comprises a light chain variable region comprising an amino acid sequence
ii. Claim 19 recites the term “nanobody”, which is a trade name or a mark used in commerce. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Appropriate correction is required.
Improper Markush Grouping
8. Claims 1-2, 12-14, 16, 19, 23, 26 and 30 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 706.03(y).
The Markush grouping of different nucleic acid molecules comprising different sequences encoding different single chain antibodies binding to Trp-68 in misfold TDP-43 comprising different SEQ ID NOs: for CDR-H1-3 and CDR-L1-3 recited in claim 1, the Markush grouping of different antibodies comprising different SEQ ID NOs: or variants thereof for VH and VL recited in a)-j) of claim 2 or the Markush grouping of sequences encoding the antibody and linker portions and targeting moiety recited in claims 16 and 23 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The recited alternative species do not share a single structural similarity, as each species of nucleic acid molecules or each species of single chain antibodies binding to Trp-68 in misfold TDP-43 or each species of sequences encoding the antibody and linker portions and targeting moiety has a different chemical structure because it comprises different amino acid sequences for CDR-H1-3 and CDR-L1-3; VH and VL or antibodies/moieties. Each nucleic acid sequence has a different amino acid composition and structure, and each encoded single chain antibody has a different binding activity to different epitopes. Thus, the nucleic acid molecules comprising sequences encoding the claimed single chain antibodies do not share a single structural similarity or biological activity. See MPEP § 706.03(y).
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112
9. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2, 12-14, 16, 19, 23, 26 and 30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claims 1-2, 12-14, 16, 19, 23, 26 and 30 are indefinite because:
i. Regarding claim 1, the phrase "preferably wherein the CDR sequences comprise SEQ ID NOs:…." in the last line of the claim renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
ii. It is unclear whether the limitation “said CDRs” and the limitation “the CDRs” recited in claim 1 refer to the same CDRs, and thus the claim is indefinite.
iii. The limitation “Trp-68 in misfolded TDP-43” recited in claim 1 is unclear because there are multiple isoforms of TDP-43 which contain amino acid sequences in different lengths and it is unclear whether Trp-68 is the same within different isoforms of TDP-43, which render the claim indefinite.
iv. Regarding claims 2 and 23, the term “a codon degenerate or optimized version” in claim 2, or the term “a codon optimized sequence” in clam 23 is a relative term which renders the claim indefinite. The term “a codon degenerate or optimized version” or “a codon optimized sequence” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Applicant fails to set forth the metes and bounds of what is encompassed within the definition of “a codon degenerate or optimized version” or “a codon optimized sequence”. Since the metes and bounds are unknown, a skilled artisan cannot envision what would be considered as “a codon degenerate or optimized version” or “a codon optimized sequence thereof” recited in the claims and within the scope of the claims. Thus, the claims are indefinite.
v. Claims 12-13 recites the limitation "the orientation" in line 1 of the claims. There is insufficient antecedent basis for this limitation in the claim.
vi. Regarding claim 14, the phrase "preferably 15 or 20 amino acids and/or is selected…." in line 2 of the claim renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
v. Regarding claim 16 the phrase "preferably linked by a targeting moiety linker,…." in line 2 of the claim renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
vii. Claim 19 contains the trademark/trade name “nanobody”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112, second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a single chain antibody and, accordingly, the identification/description is indefinite.
viii. Regarding claims 26 and 30, the phrase "preferably AAV serotype 9" in line 2 of the claim renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
ix. The rest of claims are indefinite as depending from an indefinite claim.
Claim Rejections - 35 USC § 112
10. Claims 1-2, 12-14, 16, 19, 23, 26 and 30 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
Claims 1-2, 12-14, 16, 19, 23, 26 and 30 encompass a genus of nucleic acid sequences encoding a genus of single chain antibodies binding to Trp-68 in misfolded TDP-43 (anti-Trp68-TDP-43 scAb) comprising a VH and a VL linked by a linker and wherein the orientation of the VH and VL and linker is not defined and wherein the sequence of the linker is not defined.
Claim 2 encompasses a genus of nucleic acid encoding a genus of anti-Trp68-TDP-43 scAb wherein the anti-Trp68-TDP-43 scAb does not necessarily comprise a paired set of VH and VL or a paired set of CDR-H1-3 and CDR-L1-3 having recited SEQ ID NOs: because the claimed anti-Trp68-TDP-43 scAb comprises a VH having at least 80%, 85%, 90%, 95% identity to SEQ ID NO:100 or a conservatively substituted sequence thereof, and/or a VL having at least 80%, 85%, 90%, 95% identity to SEQ ID NO:101 or a conservatively substituted sequence thereof and/or wherein the VH is encoded by a nucleotide sequence set out in SEQ ID NO:78 or a codon degenerate or optimized version thereof and /or the VL is encoded by a nucleotide sequence as set out in SEQ ID NO:79 or a codon degenerate or optimized version thereof.
Applicant has not disclosed sufficient species for the broad genus of nucleic acid sequences encoding a genus of anti-Trp68-TDP-43 scAb that comprises a VH and a VL linked by a linker with no defined sequence and no defined orientation for the VH, VL and linker.
Applicant has also not disclosed sufficient species for the broad genus of anti-Trp68-TDP-43 scAb comprising a VH variant sequences having at least 80%, 85%, 90%, 95% identity to SEQ ID NO:100 or a conservatively substituted sequence thereof, and/or a VL variant sequences having at least 80%, 85%, 90%, 95% identity to SEQ ID NO:101 or a conservatively substituted sequence thereof and/or wherein the VH is encoded by a nucleotide sequence set out in SEQ ID NO:78 or a codon degenerate or optimized version thereof and /or the VL is encoded by a nucleotide sequence as set out in SEQ ID NO:79 or a codon degenerate or optimized version thereof.
Applicant has not disclosed sufficient species for the broad genus of anti-Trp68-TDP-43 scAb comprising an amino acid sequence at least 80%, 85%, 90%, or 95% identical to the VH of SEQ ID NO:100 or a conservatively substituted sequence thereof and/or at least an amino acid sequence at least 80%, 85%, 90%, or 95% identical to the VL of SEQ ID NO:101 or a conservatively substituted sequence thereof.
The specification only discloses:
i. monoclonal antibodies 2F7, 1H3-1K3, 28H3-28K1 and 14H1-14K2 capable of binding to Trp68 in TDP-43 (tables 5 and 8; p. 39-40) and their amino acid sequences for VH and VL and HCDRs1-3 and LCDRs1-3, and DNA sequences for the VH and VL (see p. 30-35;Table 4, amino acid sequences for VH and VL; Table 2: amino acid sequence for HCDRs1-3 and LCDRs1-3, Table 3, DNA sequences for VH and VL);
ii. ScFv constructs:
a) with an N-terminal Flag tag lysosomal constructs: LYS-2F7, LYS-1H3-1K3, LYS-28H3-28K1 and LYS-14H1-14K2 comprising a lysosomal-targeting tag and their polynucleotide and amino acid sequences (table 9, p. 41-43);
b) C-terminal Flag-YPTL intrabodies YPTL-2F7, YPTL-1H3-1K3, YPTL-28H3-28K1 and YPTL-14H1-14K2 and their polynucleotide and amino acid sequences (table 10, p. 43-45);
c) C-terminal MYC tag constructs with a VL linked to a VH through a 15 amino acid linker: the VL sequence-15 amino acid ScFv linker sequence-VH-three amino acid MYC linker sequence-MYC tag: MYCL15H-2F7, MYC15H-1H3-1K3, MYCL15H-28H-288K1 and MYCL15H-14H1-14K2 and their polynucleotide and amino acid sequences (table 11; p. 45-47);
d) MYC constructs with a VH linked to a VL through a 15 amino acid linker: the VH sequence-15 amino acid ScFv linker sequence-the VL sequence-3 amino acid MYC linker sequence -MYC tag and their polynucleotide and amino acid sequences (table 12, p. 47-49);
e) MYC constructs with a VL linked to a VH through a 20 amino acid linker: the VL sequence-20 amino acid ScFv linker sequence-the VH sequence-three amino acid MYC linker sequence-MYC tag (table 13; p. 49-51);
f) MYC construct with a VH linked to a VL through a 20 amino acid linker: the VH sequence-20 amino acid ScFv linker sequence-the VL sequence-three amino acid MYC linker sequence-MYC tag and their polynucleotide and amino acid sequences (table 14, p. 51-53).
iii. overexpression of the above constructs showed strong interaction with aggregated cytoplasmic dNLS-TDP-43 but not normal nuclear TDP-43 except MYCH20L-2F7 showed lower expression (Example 13, p. 53-54).
iv. Overexpression of LYS-2F7, LYS-28H3-28K1 and LYS-14H1-14K2; YPTL-14H1-14K2; MYCH15L-2F7, MYC15H-1H3-1K3 and MYCH20L-14H1-14K intrabodies interacted with aggregated cytoplasmic dNLS-TDP43 and accelerated dNLS-TDP43 degradation (p.54, [00241]; figures 19-21).
However, the claims are not limited to the ScFv DNA constructs set forth above but also encompass structurally and functionally undefined DNA comprising structurally and functionally undefined sequences encoding a genus of anti-Trp68-TDP-43 scAb that comprises a VH and a VL linked by a linker with no defined sequence and orientation for the VH, VL and linker, or a genus of anti-Trp68-TDP-43 scAb that does not necessarily comprise a paired set of VH and VL or a paired set of CDR-H1-3 and CDR-L1-3 having recited SEQ ID NOs: or variants thereof with at least 80%~95% identity to recited SEQ ID NOs:.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is in possession of and what Applicant is claiming.
M.P.E.P. § 2163 instructs:
An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. . . .
An applicant may show possession of an invention by disclosure of drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole. . . .
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.”
This standard has not been met in this case. From the specification, it is clear that Applicant is in possession of nucleic acid sequences encoding Trp68-TDP-43 scAb that comprises defined sequences of the VH and the VL linked by a linker with a defined sequence in a defined orientation for the VH, VL and the linker as shown in Tables 9-14).
However, Applicant is not in possession of other structurally and functionally undefined DNA comprising structurally and functionally sequences encoding an anti-Trp68-TDP-43 scAb that comprises a VH and a VL linked by a linker with no defined sequence and orientation for the VH, VL and linker. Applicant is also not in possession of other structurally and functionally undefined anti-Trp68-TDP-43 scAb that do not necessarily comprise a paired set of VH and VL or a paired set of CDR-H1-3 and CDR-L1-3 having recited SEQ ID NOs: or variants thereof with at least 80%~95% identity to recited SEQ ID NOs:.
Based on Applicant’s own admission, MYCH20L-2F7 showed lower expression (Example 13, p. 53-54), and only overexpression of LYS-2F7, LYS-28H3-28K1 and LYS-14H1-14K2; YPTL-14H1-14K2; MYCH15L-2F7, MYC15H-1H3-1K3 and MYCH20L-14H1-14K intrabodies showed interaction with aggregated cytoplasmic dNLS-TDP43 and accelerated dNLS-TDP43 degradation (p.54, [00241]; figures 19-21).
The specification provides no structurally and functionally relationship or correlation between the claimed genus of nucleic acid sequences encoding anti-Trp68-TDP-43 scAb comprising a VH and a VL linked by a undefined linker sequence with no defined orientation for the VH and VL and linker and the ScFv constructs shown in Tables 9-14. The specification provides no structurally and functionally relationship or correlation between the claimed genus of nucleic acid sequences encoding structurally and functionally undefined anti-Trp68-TDP-43 scAb that do not necessarily comprise a paired set of VH and VL or a paired set of CDR-H1-3 and CDR-L1-3 having recited SEQ ID NOs: or variants thereof with at least 80%~95% identity to recited SEQ ID NOs: and the ScFv constructs shown in Tables 9-14..
It is known in the art that a single amino acid change on a molecule or protein can abolish the binding activity of the molecule or protein. For example, a substitution of lysine residue by glutamic acid at position 118 of acidic fibroblast growth factor results in a substantial loss of its biological activity including the binding ability to heparin and its receptor (Burgess et al. J of Cell Bio. 1990, 111:2129-2138). Although many amino acid substitutions are possible in any given protein, the position of where such amino acid substitutions can be made is critical for maintaining the function of a protein; i.e. only certain positions can tolerate conservative substitutions without changing the relationship of three dimensional structure and function of the protein (col 2, p. 1306, Bowie et al. Science, 1990, 247:1306-1310). Even if an active or binding site were identified in the specification, they may not be sufficient, as the ordinary artisan would not immediately recognize that an active or binding site must assume the proper three-dimensional configuration to be active because conformation is dependent upon surrounding residues; i.e. substitution of non-essential residues can often destroy activity. In addition to a core determinant sequence, the protein-protein interaction also relies on the flanking or noncontiguous residues (see p. 445 the second column, first paragraph, Pawson et al. 2003, Science 300:445-452). The optimal binding motif for a domain is not necessarily suitable for physiological or in vivo interaction. The predictive data always need to be validated by actual analyses in cells (see p. 445, the third column, second paragraph, Pawson et al. 2003, Science 300:445-452). Alaoui-lsmaili teaches that designing a mutein having predictable activities is difficult because of the complexity of the interactions between ligands and receptors (Alaoui-lsmaili et al., Cytokine Growth Factor Rev. 2009; 20:501-507). For example, given the complexity of BMP-BMP receptor interactions, it is difficult to design BMPs with improved affinity and/or specificity for one specific receptor. More importantly, predicting the in vivo biological activity of such altered BMPs remains a challenging undertaking (see p. 502, right col., 2th paragraph). Further, when multiple mutations are introduced, there is even less predictability because Guo et al. teaches that the effects of mutations on protein function are largely additive (see p. 9207, left col., 2th paragraph, Guo et al., PNAS 2004; 101:9205-9210). Moreover, even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proc. Natl. Acad. Sci. USA 1982 Vol. 79: page 1979). Rudikoff et al. teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. Applicant fails to teach what structures/amino acid sequences are for the claimed structurally and functionally undefined DNA comprising structurally and functionally undefined sequences encoding anti-Trp68-TDP-43 scAb that comprises a VH and a VL linked by a linker with no defined sequence and with no defined orientation for the VH and VL and linker, or what structures/amino acid sequences are for the claimed structurally and functionally undefined anti-Trp68-TDP-43 scAb that do not necessarily comprise a paired set of VH and VL or a paired set of CDR-H1-3 and CDR-L1-3 having recited SEQ ID NOs: or variants thereof with at least 80%~95% identity to recited SEQ ID NOs:.
Neither the specification nor the prior art teaches what other structurally and functionally undefined DNAs comprising structurally and functionally sequences encoding anti-Trp68-TDP-43 scAb that comprises a VH and a VL linked by a linker with no defined sequence and with no defined orientation for the VH and VL and linker are, and what structures/amino acid sequences are for the claimed structurally and functionally undefined anti-Trp68-TDP-43 scAb that do not necessarily comprise a paired set of VH and VL or a paired set of CDR-H1-3 and CDR-L1-3 having recited SEQ ID NOs: or variants thereof with at least 80%~95% identity to recited SEQ ID NOs: are.
The specification provides no identification of any particular portion of the structure that must be conserved for the claimed DNAs comprising structurally and functionally sequences encoding anti-Trp68-TDP-43 scAb that comprises a VH and a VL linked by a linker with no defined sequence and with no defined orientation for the VH and VL and linker, or for anti-Trp68-TDP-43 scAb that do not necessarily comprise a paired set of VH and VL or a paired set of CDR-H1-3 and CDR-L1-3 having recited SEQ ID NOs: or variants thereof with at least 80%~95% identity to recited SEQ ID NOs:. The instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of DNAs comprising structurally and functionally sequences encoding anti-Trp68-TDP-43 scAb that comprises a VH and a VL linked by a linker with no defined sequence and with no defined orientation for the VH and VL and linker, or the claimed genus of anti-Trp68-TDP-43 scAb that do not necessarily comprise a paired set of VH and VL or a paired set of CDR-H1-3 and CDR-L1-3 having recited SEQ ID NOs: or variants thereof with at least 80%~95% identity to recited SEQ ID NOs:. There is no description of the conserved regions which are critical to the function of the genus claimed. There is no description of the sites at which variability may be tolerated and there is no information regarding the relation of the structure of other DNAs encoding anti-Trp68-TDP-43 scAb that comprises a VH and a VL linked by a linker with no defined sequence and with no defined orientation for the VH and VL and linker, or the claimed genus of anti-Trp68-TDP-43 scAb that do not necessarily comprise a paired set of VH and VL or a paired set of CDR-H1-3 and CDR-L1-3 having recited SEQ ID NOs: or variants thereof with at least 80%~95% identity to recited SEQ ID NOs:.. Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other DNAs encoding anti-Trp68-TDP-43 scAb that comprises a VH and a VL linked by a linker with no defined sequence and with no defined orientation for the VH and VL and linker might be or what other anti-Trp68-TDP-43 scAb that do not necessarily comprise a paired set of VH and VL or a paired set of CDR-H1-3 and CDR-L1-3 having recited SEQ ID NOs: or variants thereof with at least 80%~95% identity to recited SEQ ID NOs: might be. Since the common characteristics/features of other DNAs or anti-Trp68-TDP-43 scAb that do not necessarily comprise a paired set of VH and VL or a paired set of CDR-H1-3 and CDR-L1-3 having recited SEQ ID NOs: or variants thereof with at least 80%~95% identity to recited SEQ ID NOs: are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the genus of DNAs encoding anti-Trp68-TDP-43 scAb that comprises a VH and a VL linked by a linker with no defined sequence and with no defined orientation for the VH and VL and linker or the claimed genus of anti-Trp68-TDP-43 scAb that do not necessarily comprise a paired set of VH and VL or a paired set of CDR-H1-3 and CDR-L1-3 having recited SEQ ID NOs: or variants thereof with at least 80%~95% identity to recited SEQ ID NOs:.
Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of DNAs encoding anti-Trp68-TDP-43 scAb that comprises a VH and a VL linked by a linker with no defined sequence and with no defined orientation for the VH and VL and linker or the claimed genus of anti-Trp68-TDP-43 scAb that do not necessarily comprise a paired set of VH and VL or a paired set of CDR-H1-3 and CDR-L1-3 having recited SEQ ID NOs: or variants thereof with at least 80%~95% identity to recited SEQ ID NOs:, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483.
Therefore, the claimed DNAs encoding anti-Trp68-TDP-43 scAb that comprises a VH and a VL linked by a linker and the claimed anti-Trp68-TDP-43 scAb that do not necessarily comprise a paired set of VH and VL or a paired set of CDR-H1-3 and CDR-L1-3 having recited SEQ ID NOs: or variants thereof with at least 80%~95% identity to recited SEQ ID NOs have not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 102
12. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 19, 26 and 30 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Cashman et al. (WO2020118458, published on June 18, 2020, priority Dec 14, 2018, as in IDS).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Cashman et al. (WO2020118458) teach nucleic acids or vectors encoding an antibody binding to misfolded TDP-43 (mis-TDP-43) and specifically binding to an epitope comprising at least W68 in the context of DAGWGNL (SEQ ID NO:1) (i.e. anti-misTDP-43-W68 antibody) (see paragraphs [00163]-[0182] [0037]), wherein the anti-misTDP-43-W68 antibody includes a single chain antibody including scFv or ds-scFv, minibodies, or diabodies or humanized as recited in claim 19 (see paragraphs, [00130]; [00132]; [00135]-[00137]; [00140]; [00156]; [0034]), and wherein the single chain antibody is produced by recombinant expression techniques, which comprise polynucleotides encoding the single chain antibody (see paragraphs [00156]; [00163]-[0182]; [0086]-[0088]; [0092]-[0093]; [00114]-[00119]; [00121]-[130]), and the single chain antibody contains a structure of a VH and a VL linked with a linker or spacer as in claims 1 (see paragraph [00130]), and wherein the VH comprises the amino acid sequence of SEQ ID NO:100, which is 100% identical to instant SEQ ID NO:100 that comprises instant SEQ ID NOs: 16-18, and the VL comprises the amino acid sequence of SEQ ID NO:101, which is 100% identical to instant SEQ ID NO:101 that comprises instant SEQ ID NOs: 19-21 as recited in claims 1-2 or wherein the VH is encoded by a nucleic acid sequence that is 100% identical to instant SEQ ID NO:78 and the VL is encoded by a nucleic acid sequence that is 100% identical to instant SEQ ID NO:79 (see the sequence alignment below). Thus, the nucleic acid encoding the anti-misTDP-43-W68 disclosed by Cashman meets the limitations recited in instant claims. Cashman also teaches an expression cassette or vector comprising the nucleic acid of claim 1 and a cell recombinantly expressing the scFv, and wherein the vector includes a lentiviral vector or adeno-associated (AAV) vector including AAV9 as in claims 26 and 30 (see paragraphs [0088]; [00171]; [00180]; [00231]). Thus, claims 1-2, 19, 26 and 30 are anticipated by Cashman (WO2020118458).
The sequence search results disclose as follows:
SEQ ID NO:100
BHW55549
(NOTE: this sequence has 1 duplicate in the database searched)
ID BHW55549 standard; protein; 118 AA.
XX
AC BHW55549;
XX
DT 06-AUG-2020 (first entry)
XX
DE Anti-TDP-43 monoclonal antibody (clone 14) VH region, SEQ 100.
XX
KW Protein aggregation; Protein misfolding; TAR DNA binding protein 43;
KW TAR element DNA binding protein of 43 kDa; TDP-43 protein;
KW antibody production; antibody therapy; atrophy; expression;
KW frontotemporal dementia; frontotemporal lobar degeneration;
KW heavy chain variable region; immunoconjugate;
KW limbic-predominant age-related TDP-43 encephalopathy;
KW monoclonal antibody; motor neurone disease; neurodegenerative disease;
KW neuroprotective; primary lateral sclerosis; protein detection;
KW protein inhibition; screening; therapeutic;
KW transactive response element DNA binding protein of 43 kDa.
XX
OS Oryctolagus cuniculus.
XX
CC PN WO2020118458-A1.
XX
CC PD 18-JUN-2020.
XX
CC PF 16-DEC-2019; 2019WO-CA051823.
XX
PR 14-DEC-2018; 2018US-0779904P.
PR 21-OCT-2019; 2019US-0923789P.
XX
CC PA (UYBR ) UNIV BRITISH COLUMBIA.
CC PA (PROM-) PROMIS NEUROSCIENCES INC.
XX
CC PI Cashman NR, Kaplan J;
XX
DR WPI; 2020-54009D/054.
DR N-PSDB; BHW55527.
XX
CC PT New antibody useful in composition for treating human suspected of having
CC PT transactive response DNA binding protein-43 proteinopathy e.g.
CC PT amyotrophic lateral sclerosis, and frontotemporal lobar degeneration.
XX
CC PS Claim 16; SEQ ID NO 100; 88pp; English.
XX
CC The present invention relates to a novel antibody, useful for treating
CC transactive response (TAR) element DNA binding protein of 43 kDa (TDP-43)
CC proteinopathy in a subject. The antibody specifically binds with TDP-43
CC epitope of SEQ ID NOs: 1-6 (see BHW55450-BHW55455), where the antibody
CC comprises a heavy chain variable region (VH) and light chain variable
CC region (VL) with their corresponding complementarity determining regions
CC (CDRs) of SEQ ID NOs: 10-51 (see BHW55459-BHW55500), SEQ ID NOs: 120-125
CC (see BHW55569-BHW55574), SEQ ID NOs: 130-135 (see BHW55579-BHW55584), and
CC SEQ ID NOs: 140-145 (see BHW55589-BHW55594). The invention further
CC claims: (1) an immunoconjugate comprising the antibody; (2) an isolated
CC peptide comprising the epitope; (3) an immunogen comprising the peptide;
CC (4) an isolated nucleic acid encoding the immunogen; (5) a cell
CC recombinantly expressing the peptide; (6) a composition comprising the
CC isolated peptide and antibody; (7) a method for treating a subject with
CC TDP-43 proteinopathy by administering an effective amount of the antibody
CC ; (8) a method for inhibiting TDP-43 cell transmission by administering
CC the antibody; (9) a kit; (10) a method for making and/or preparing the
CC antibody; (11) an antibody; and (12) a method for determining if a sample
CC suspected of comprising cytosolic/aggregated and/or a misfolded TDP-43
CC contains cystolic/aggregated or misfolded TDP-43. The antibody is useful
CC for treating TDP-43 proteinopathy such as amyotrophic lateral sclerosis
CC (ALS), frontotemporal lobar degeneration (FTLD-TDP), primary lateral
CC sclerosis, progressive muscular atrophy, and limbic-predominant age-
CC related TDP-43 encephalopathy (LATE); and detecting misfolded TDP-43.
XX
SQ Sequence 118 AA;
Query Match 100.0%; Score 628; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QEQLEESGGDLVKPEGSLTLTCTASGFSFSSNYVMCWVRQAPGKGLEWVACIWFAGIVDT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QEQLEESGGDLVKPEGSLTLTCTASGFSFSSNYVMCWVRQAPGKGLEWVACIWFAGIVDT 60
Qy 61 TYYATWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARNPVGSVNLWGQGTLVTVS 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TYYATWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARNPVGSVNLWGQGTLVTVS 118
SEQ ID NO:101
BHW55550
(NOTE: this sequence has 1 duplicate in the database searched)
ID BHW55550 standard; protein; 110 AA.
XX
AC BHW55550;
XX
DT 06-AUG-2020 (first entry)
XX
DE Anti-TDP-43 monoclonal antibody (clone 14) VL region, SEQ 101.
XX
KW Protein aggregation; Protein misfolding; TAR DNA binding protein 43;
KW TAR element DNA binding protein of 43 kDa; TDP-43 protein;
KW antibody production; antibody therapy; atrophy; expression;
KW frontotemporal dementia; frontotemporal lobar degeneration;
KW immunoconjugate; light chain variable region;
KW limbic-predominant age-related TDP-43 encephalopathy;
KW monoclonal antibody; motor neurone disease; neurodegenerative disease;
KW neuroprotective; primary lateral sclerosis; protein detection;
KW protein inhibition; screening; therapeutic;
KW transactive response element DNA binding protein of 43 kDa.
XX
OS Oryctolagus cuniculus.
XX
CC PN WO2020118458-A1.
XX
CC PD 18-JUN-2020.
XX
CC PF 16-DEC-2019; 2019WO-CA051823.
XX
PR 14-DEC-2018; 2018US-0779904P.
PR 21-OCT-2019; 2019US-0923789P.
XX
CC PA (UYBR ) UNIV BRITISH COLUMBIA.
CC PA (PROM-) PROMIS NEUROSCIENCES INC.
XX
CC PI Cashman NR, Kaplan J;
XX
DR WPI; 2020-54009D/054.
DR N-PSDB; BHW55528.
XX
CC PT New antibody useful in composition for treating human suspected of having
CC PT transactive response DNA binding protein-43 proteinopathy e.g.
CC PT amyotrophic lateral sclerosis, and frontotemporal lobar degeneration.
XX
CC PS Claim 16; SEQ ID NO 101; 88pp; English.
XX
CC The present invention relates to a novel antibody, useful for treating
CC transactive response (TAR) element DNA binding protein of 43 kDa (TDP-43)
CC proteinopathy in a subject. The antibody specifically binds with TDP-43
CC epitope of SEQ ID NOs: 1-6 (see BHW55450-BHW55455), where the antibody
CC comprises a heavy chain variable region (VH) and light chain variable
CC region (VL) with their corresponding complementarity determining regions
CC (CDRs) of SEQ ID NOs: 10-51 (see BHW55459-BHW55500), SEQ ID NOs: 120-125
CC (see BHW55569-BHW55574), SEQ ID NOs: 130-135 (see BHW55579-BHW55584), and
CC SEQ ID NOs: 140-145 (see BHW55589-BHW55594). The invention further
CC claims: (1) an immunoconjugate comprising the antibody; (2) an isolated
CC peptide comprising the epitope; (3) an immunogen comprising the peptide;
CC (4) an isolated nucleic acid encoding the immunogen; (5) a cell
CC recombinantly expressing the peptide; (6) a composition comprising the
CC isolated peptide and antibody; (7) a method for treating a subject with
CC TDP-43 proteinopathy by administering an effective amount of the antibody
CC ; (8) a method for inhibiting TDP-43 cell transmission by administering
CC the antibody; (9) a kit; (10) a method for making and/or preparing the
CC antibody; (11) an antibody; and (12) a method for determining if a sample
CC suspected of comprising cytosolic/aggregated and/or a misfolded TDP-43
CC contains cystolic/aggregated or misfolded TDP-43. The antibody is useful
CC for treating TDP-43 proteinopathy such as amyotrophic lateral sclerosis
CC (ALS), frontotemporal lobar degeneration (FTLD-TDP), primary lateral
CC sclerosis, progressive muscular atrophy, and limbic-predominant age-
CC related TDP-43 encephalopathy (LATE); and detecting misfolded TDP-43.
XX
SQ Sequence 110 AA;
Query Match 100.0%; Score 588; Length 110;
Best Local Similarity 100.0%;
Matches 110; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 VMTQTPSSKSVPVGGSVTINCQASESVYSNNRLSWYQQKPGQPPKLLIYYASTLESGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 VMTQTPSSKSVPVGGSVTINCQASESVYSNNRLSWYQQKPGQPPKLLIYYASTLESGVPS 60
Qy 61 RFKGSGFGTHFTLTISGAQCDDAATYYCAGWRGARTDGVDFGGGTEVVVK 110
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFKGSGFGTHFTLTISGAQCDDAATYYCAGWRGARTDGVDFGGGTEVVVK 110
SEQ ID NO:78
BHW55527
(NOTE: this sequence has 1 duplicate in the database searched)
ID BHW55527 standard; DNA; 353 BP.
XX
AC BHW55527;
XX
DT 06-AUG-2020 (first entry)
XX
DE Anti-TDP-43 monoclonal antibody (clone 14) VH DNA, SEQ 78.
XX
KW Protein aggregation; Protein misfolding; TAR DNA binding protein 43;
KW TAR element DNA binding protein of 43 kDa; TDP-43 protein;
KW antibody production; antibody therapy; atrophy; coding sequence; ds;
KW expression; frontotemporal dementia; frontotemporal lobar degeneration;
KW heavy chain variable region; immunoconjugate; immunoglobulin gene;
KW limbic-predominant age-related TDP-43 encephalopathy;
KW motor neurone disease; neurodegenerative disease; neuroprotective;
KW primary lateral sclerosis; protein detection; protein inhibition;
KW screening; therapeutic;
KW transactive response element DNA binding protein of 43 kDa.
XX
OS Oryctolagus cuniculus.
XX
CC PN WO2020118458-A1.
XX
CC PD 18-JUN-2020.
XX
CC PF 16-DEC-2019; 2019WO-CA051823.
XX
PR 14-DEC-2018; 2018US-0779904P.
PR 21-OCT-2019; 2019US-0923789P.
XX
CC PA (UYBR ) UNIV BRITISH COLUMBIA.
CC PA (PROM-) PROMIS NEUROSCIENCES INC.
XX
CC PI Cashman NR, Kaplan J;
XX
DR WPI; 2020-54009D/054.
DR P-PSDB; BHW55549.
XX
CC PT New antibody useful in composition for treating human suspected of having
CC PT transactive response DNA binding protein-43 proteinopathy e.g.
CC PT amyotrophic lateral sclerosis, and frontotemporal lobar degeneration.
XX
CC PS Claim 16; SEQ ID NO 78; 88pp; English.
XX
CC The present invention relates to a novel antibody, useful for treating
CC transactive response (TAR) element DNA binding protein of 43 kDa (TDP-43)
CC proteinopathy in a subject. The antibody specifically binds with TDP-43
CC epitope of SEQ ID NOs: 1-6 (see BHW55450-BHW55455), where the antibody
CC comprises a heavy chain variable region (VH) and light chain variable
CC region (VL) with their corresponding complementarity determining regions
CC (CDRs) of SEQ ID NOs: 10-51 (see BHW55459-BHW55500), SEQ ID NOs: 120-125
CC (see BHW55569-BHW55574), SEQ ID NOs: 130-135 (see BHW55579-BHW55584), and
CC SEQ ID NOs: 140-145 (see BHW55589-BHW55594). The invention further
CC claims: (1) an immunoconjugate comprising the antibody; (2) an isolated
CC peptide comprising the epitope; (3) an immunogen comprising the peptide;
CC (4) an isolated nucleic acid encoding the immunogen; (5) a cell
CC recombinantly expressing the peptide; (6) a composition comprising the
CC isolated peptide and antibody; (7) a method for treating a subject with
CC TDP-43 proteinopathy by administering an effective amount of the antibody
CC ; (8) a method for inhibiting TDP-43 cell transmission by administering
CC the antibody; (9) a kit; (10) a method for making and/or preparing the
CC antibody; (11) an antibody; and (12) a method for determining if a sample
CC suspected of comprising cytosolic/aggregated and/or a misfolded TDP-43
CC contains cystolic/aggregated or misfolded TDP-43. The antibody is useful
CC for treating TDP-43 proteinopathy such as amyotrophic lateral sclerosis
CC (ALS), frontotemporal lobar degeneration (FTLD-TDP), primary lateral
CC sclerosis, progressive muscular atrophy, and limbic-predominant age-
CC related TDP-43 encephalopathy (LATE); and detecting misfolded TDP-43.
XX
SQ Sequence 353 BP; 71 A; 98 C; 106 G; 78 T; 0 U; 0 Other;
Query Match 100.0%; Score 353; Length 353;
Best Local Similarity 100.0%;
Matches 353; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 CAGGAGCAGCTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGAGGGATCCCTGACACTC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 CAGGAGCAGCTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGAGGGATCCCTGACACTC 60
Qy 61 ACCTGCACAGCCTCTGGATTCTCCTTCAGTAGCAACTACGTGATGTGCTGGGTCCGCCAG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ACCTGCACAGCCTCTGGATTCTCCTTCAGTAGCAACTACGTGATGTGCTGGGTCCGCCAG 120
Qy 121 GCTCCAGGGAAGGGGCTGGAGTGGGTCGCATGCATTTGGTTTGCTGGTATTGTTGATACT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GCTCCAGGGAAGGGGCTGGAGTGGGTCGCATGCATTTGGTTTGCTGGTATTGTTGATACT 180
Qy 181 ACTTACTACGCGACCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ACTTACTACGCGACCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACG 240
Qy 241 GTGACTCTGCAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GTGACTCTGCAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGA 300
Qy 301 AATCCTGTTGGTAGTGTGAACTTGTGGGGCCAGGGCACCCTGGTCACCGTCTC 353
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 AATCCTGTTGGTAGTGTGAACTTGTGGGGCCAGGGCACCCTGGTCACCGTCTC 353
SEQ ID NO:79
BHW55528
(NOTE: this sequence has 1 duplicate in the database searched)
ID BHW55528 standard; DNA; 331 BP.
XX
AC BHW55528;
XX
DT 06-AUG-2020 (first entry)
XX
DE Anti-TDP-43 monoclonal antibody (clone 14) VL DNA, SEQ 79.
XX
KW Protein aggregation; Protein misfolding; TAR DNA binding protein 43;
KW TAR element DNA binding protein of 43 kDa; TDP-43 protein;
KW antibody production; antibody therapy; atrophy; coding sequence; ds;
KW expression; frontotemporal dementia; frontotemporal lobar degeneration;
KW immunoconjugate; immunoglobulin gene; light chain variable region;
KW limbic-predominant age-related TDP-43 encephalopathy;
KW motor neurone disease; neurodegenerative disease; neuroprotective;
KW primary lateral sclerosis; protein detection; protein inhibition;
KW screening; therapeutic;
KW transactive response element DNA binding protein of 43 kDa.
XX
OS Oryctolagus cuniculus.
XX
CC PN WO2020118458-A1.
XX
CC PD 18-JUN-2020.
XX
CC PF 16-DEC-2019; 2019WO-CA051823.
XX
PR 14-DEC-2018; 2018US-0779904P.
PR 21-OCT-2019; 2019US-0923789P.
XX
CC PA (UYBR ) UNIV BRITISH COLUMBIA.
CC PA (PROM-) PROMIS NEUROSCIENCES INC.
XX
CC PI Cashman NR, Kaplan J;
XX
DR WPI; 2020-54009D/054.
DR P-PSDB; BHW55550.
XX
CC PT New antibody useful in composition for treating human suspected of having
CC PT transactive response DNA binding protein-43 proteinopathy e.g.
CC PT amyotrophic lateral sclerosis, and frontotemporal lobar degeneration.
XX
CC PS Claim 16; SEQ ID NO 79; 88pp; English.
XX
CC The present invention relates to a novel antibody, useful for treating
CC transactive response (TAR) element DNA binding protein of 43 kDa (TDP-43)
CC proteinopathy in a subject. The antibody specifically binds with TDP-43
CC epitope of SEQ ID NOs: 1-6 (see BHW55450-BHW55455), where the antibody
CC comprises a heavy chain variable region (VH) and light chain variable
CC region (VL) with their corresponding complementarity determining regions
CC (CDRs) of SEQ ID NOs: 10-51 (see BHW55459-BHW55500), SEQ ID NOs: 120-125
CC (see BHW55569-BHW55574), SEQ ID NOs: 130-135 (see BHW55579-BHW55584), and
CC SEQ ID NOs: 140-145 (see BHW55589-BHW55594). The invention further
CC claims: (1) an immunoconjugate comprising the antibody; (2) an isolated
CC peptide comprising the epitope; (3) an immunogen comprising the peptide;
CC (4) an isolated nucleic acid encoding the immunogen; (5) a cell
CC recombinantly expressing the peptide; (6) a composition comprising the
CC isolated peptide and antibody; (7) a method for treating a subject with
CC TDP-43 proteinopathy by administering an effective amount of the antibody
CC ; (8) a method for inhibiting TDP-43 cell transmission by administering
CC the antibody; (9) a kit; (10) a method for making and/or preparing the
CC antibody; (11) an antibody; and (12) a method for determining if a sample
CC suspected of comprising cytosolic/aggregated and/or a misfolded TDP-43
CC contains cystolic/aggregated or misfolded TDP-43. The antibody is useful
CC for treating TDP-43 proteinopathy such as amyotrophic lateral sclerosis
CC (ALS), frontotemporal lobar degeneration (FTLD-TDP), primary lateral
CC sclerosis, progressive muscular atrophy, and limbic-predominant age-
CC related TDP-43 encephalopathy (LATE); and detecting misfolded TDP-43.
XX
SQ Sequence 331 BP; 75 A; 84 C; 94 G; 78 T; 0 U; 0 Other;
Query Match 100.0%; Score 331; Length 331;
Best Local Similarity 100.0%;
Matches 331; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GTGATGACCCAGACTCCATCTTCCAAGTCTGTCCCTGTGGGAGGCTCAGTCACCATCAAT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GTGATGACCCAGACTCCATCTTCCAAGTCTGTCCCTGTGGGAGGCTCAGTCACCATCAAT 60
Qy 61 TGCCAGGCCAGTGAGAGTGTTTATAGTAACAACCGCTTATCCTGGTATCAGCAGAAACCA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TGCCAGGCCAGTGAGAGTGTTTATAGTAACAACCGCTTATCCTGGTATCAGCAGAAACCA 120
Qy 121 GGGCAGCCTCCTAAGCTCCTGATCTATTATGCATCCACTCTGGAATCTGGGGTCCCATCG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GGGCAGCCTCCTAAGCTCCTGATCTATTATGCATCCACTCTGGAATCTGGGGTCCCATCG 180
Qy 181 CGGTTCAAAGGCAGTGGATTTGGGACACACTTCACTCTCACCATCAGCGGCGCGCAGTGT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 CGGTTCAAAGGCAGTGGATTTGGGACACACTTCACTCTCACCATCAGCGGCGCGCAGTGT 240
Qy 241 GACGATGCTGCCACTTACTACTGTGCAGGATGGAGAGGTGCTAGGACTGATGGTGTAGAT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GACGATGCTGCCACTTACTACTGTGCAGGATGGAGAGGTGCTAGGACTGATGGTGTAGAT 300
Qy 301 TTCGGCGGAGGGACCGAGGTGGTGGTCAAAG 331
|||||||||||||||||||||||||||||||
Db 301 TTCGGCGGAGGGACCGAGGTGGTGGTCAAAG 331
Claim Rejections - 35 USC § 103
13. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 12-14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Cashman et al. (WO2020118458, as in IDS) in view of Skrlj et al. (Appl. Biochem. Biotechnol., 2013; 169:159-169. DOI 10.1007/s12010-012-9962-7) and Walensky et al. (US Patent No. 11952432, issued Apr 9, 2024, priority Feb 7, 2018).
Cashman is set forth above but fail to teach the orientation of the VH, VL and linker is VH-linker-VL or VL-linker-VH as in claims 12-13, or wherein the linker is about 10-25 amino acids including (GGGGS)3 (SEQ ID NO:180), (GGGGS)4 (SEQ ID NO:181) or GSTGGGGSGKPGSGEGGGGS (SEQ ID NO:182) as in claim 14 or cell-penetrating peptide as in claim 16.
Skrlj et al. teach a recombinant ScFv comprising the VH-a linker -the VL or the VL-linker-the VH wherein the linker is (GGGGS)3 or the VH-linker-CPP-linker-the VL for better crossing blood-brain-barrire (BBB) and targeting to prion protein in the brain and a DNA construct encoding the ScFV (see p.160-161; p. 163-165; p.166-167).
Walensky et al. (US11952432) teach a ScFv fusion protein comprising an ScFv antibody, a linker, a cell permeable stapled peptide (CCP) including lysosomal targeting peptide for subcellular delivery of scFv (see col.3, lines 1-3; lines 24-27; lines 42-col.4, line 8; col. 5, line14-25; col.8, lines 31-51; col. 28-32, Examples 1-3), wherein the linker includes (GGGGS)3 (SEQ ID NO:180), (GGGGS)4 (SEQ ID NO:181) in claim 14 (col. 12, line 62-col.13, line 57) and wherein the lysosomal targeting peptide is a CCP in claim 23 (see col.3, lines 1-3; lines 24-27; lines 42-col.4, line 8; col. 5, line14-25; col.8, lines 31-51).
A person of ordinary skill in the art would have recognized that selecting and applying the known ScFv structure comprising VH-linker-VL or VL-linker-VH or the known ScFv fusion protein comprising the ScFv antibody, a linker, a cell permeable stapled peptide (CCP) including lysosomal targeting peptide, the known linker includes (GGGGS)3 (SEQ ID NO:180), (GGGGS)4 (SEQ ID NO:181) and the known CCP as a lysosomal targeting peptide for better subcellular delivery of scFv and the known technique disclosed by Skrlj and Walensky to the Cashman’s ScFv DNA construct would have yielded the predictable result of ScFv fusion protein comprising an ScFv antibody, a linker, a cell permeable stapled peptide (CCP) including lysosomal targeting peptide for subcellular delivery of scFv, and resulted in an improved product for better subcellular delivery of scFv to target lysosomes or lysosomal compartments.
Using and including the known ScFv structure comprising VH-linker-VL or VL-linker-VH or the known ScFv fusion protein comprising the ScFv antibody, a linker, a cell permeable stapled peptide (CCP) including lysosomal targeting peptide, the known linker includes (GGGGS)3 (SEQ ID NO:180), (GGGGS)4 (SEQ ID NO:181) and the known CCP as a lysosomal targeting peptide in the Cashman’s ScFv DNA construct would provide better subcellular delivery of scFv and lysosomal targeting to TDP-43 in the brain and expand application of the Cashman’s DNA for better delivery of anti-misTDP-43-W68 single chain antibody and would increase patient’s satisfaction with treatment using the anti-misTDP-43-W68 single chain antibody.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known ScFv structure comprising VH-linker-VL or VL-linker-VH or the known ScFv fusion protein comprising the ScFv antibody, a linker, a cell permeable stapled peptide (CCP) including lysosomal targeting peptide, the known linker includes (GGGGS)3 (SEQ ID NO:180), (GGGGS)4 (SEQ ID NO:181) and the known CCP as a lysosomal targeting peptide for better subcellular delivery of scFv and the known technique disclosed by Skrlj and Walensky to the Cashman’s ScFv DNA construct, and yield the predictable result of a DNA construct encoding anti-misTDP-43-W68 single chain antibody comprising the structure of VH-linker-VL or the structure of VL-linker-VH as in claims 12-13, and wherein the linker is about 10-25 amino acids including (GGGGS)3 (SEQ ID NO:180), (GGGGS)4 (SEQ ID NO:181) or GSTGGGGSGKPGSGEGGGGS (SEQ ID NO:182) as in claim 14 or cell-penetrating peptide as in claim 16.
14. Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Cashman et al. (WO2020118458, as in IDS) in view of Skrlj et al. (2013) and Walensky et al. (US11952432) as applied to claims 12-14 and 16, and further in view of August et al. (WO200280851, published Oct 17, 2002).
Cashman, Skrlj and Walensky are set forth above but fail to teach that the lysosomal targeting sequence has an amino acid sequence of SEQ ID NO:174 recited in claim16.
August et al. (WO200280851) teach the use of a lysosomal targeting sequence having the amino acid sequence of instant SEQ ID NO:174 as recited in claim16 (see the sequence alignment below).
A person of ordinary skill in the art would have recognized that selecting and applying the known lysosomal targeting sequence having the amino acid sequence of instant SEQ ID NO:174 and the known technique disclosed by August to the DNA construct encoding anti-misTDP-43-W68 of Cashman, Skrlj and Walensky would have yielded the predictable result of a ScFv fusion protein comprising an ScFv antibody, a linker, a cell permeable stapled peptide (CCP) including lysosomal targeting peptide having the sequence of SEQ ID NO:174 for subcellular delivery of scFv, and resulted in an improved product for better subcellular delivery of scFv to target lysosomes or lysosomal compartments.
Using and including the known lysosomal targeting sequence having the amino acid sequence of instant SEQ ID NO:174 and the known technique disclosed by August to the DNA construct encoding anti-misTDP-43-W68 of Cashman, Skrlj and Walensky would provide better subcellular delivery of scFv and lysosomal targeting to TDP-43 in the brain and expand application of the Cashman, Skrlj and Walensky’s DNA for better delivery of anti-misTDP-43-W68 single chain antibody and would increase patient’s satisfaction with treatment using the anti-misTDP-43-W68 single chain antibody.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known lysosomal targeting sequence having the amino acid sequence of instant SEQ ID NO:174 and the known technique disclosed by August to the DNA construct encoding anti-misTDP-43-W68 of Cashman, Skrlj and Walensky, and yield the predictable result of a DNA construct encoding anti-misTDP-43-W68 single chain antibody comprising the structure of VH-linker-VL or the structure of VL-linker-VH as in claims 12-13, and wherein the linker is about 10-25 amino acids including (GGGGS)3 (SEQ ID NO:180), (GGGGS)4 (SEQ ID NO:181) or GSTGGGGSGKPGSGEGGGGS (SEQ ID NO:182) as in claim 14 or lysosomal targeting sequence having the amino acid sequence of SEQ ID NO:174 or cell-penetrating peptide as in claim 16.
SEQ ID NO:174
AAE14843
(NOTE: this sequence has 10 duplicates in the database searched.
See complete list at the end of this report)
ID AAE14843 standard; peptide; 10 AA.
XX
AC AAE14843;
XX
DT 24-MAR-2003 (first entry)
XX
DE CD63 cytoplasmic tail.
XX
KW Chimera; vaccine; trafficking domain; endosome; lysosome; cancer;
KW autoimmune disease; allergic reaction; transplant; graft;
KW hypersensitivity; congenital disease; lumenal domain; CD63;
KW lysosomal membrane protein; immune response; cytoplasmic tail.
XX
OS Unidentified.
XX
FH Key Location/Qualifiers
FT Domain 7..10
FT /label= Tyr_motif
FT /note= "Targets molecules to lysosome"
XX
CC PN WO200280851-A2.
XX
CC PD 17-OCT-2002.
XX
CC PF 05-APR-2002; 2002WO-US010757.
XX
PR 05-APR-2001; 2001US-0281607P.
PR 05-APR-2001; 2001US-0281608P.
PR 05-APR-2001; 2001US-0281621P.
XX
CC PA (UYJO ) UNIV JOHNS HOPKINS.
XX
CC PI August T, Marques E;
XX
DR WPI; 2003-058464/05.
XX
CC PT Novel chimeric protein for treating cancer, comprises antigen sequence,
CC PT and trafficking domain that directs both membrane and non-membrane
CC PT proteins to endosomal compartment or trafficking domain of endocytic
CC PT receptor.
XX
CC PS Disclosure; Page 32; 102pp; English.
XX
CC The invention provides chimeric proteins and nucleic acids encoding these
CC which can be used to generate vaccines against selected antigens. The
CC chimeric protein comprises an antigen domain having at least one epitope,
CC and a trafficking domain that directs both membrane and non-membrane
CC proteins to an endosomal/lysosomal compartment in a cell and/or to a
CC lysosome-related organelle. The antigen used in the chimeric protein is
CC taken from a pathogenic organism, e.g. HIV, a cancer-specific polypeptide
CC or a molecule associated with an abnormal physiological response (e.g.
CC autoimmune disease, an allergic reaction, cancer, reaction to a
CC transplant or graft, hypersensitivity reaction, or congenital disease).
CC The trafficking domain comprises a lumenal domain of a lysosomal
CC associated membrane protein (LAMP). Alternatively, or additionally, the
CC protein comprises a trafficking domain of an endocytic receptor. The
CC vaccine (DNA, RNA, protein) can be used to modulate an immune response
CC against any kind of antigen. The invention also provides a method for
CC treating a patient with cancer by providing a chimeric protein comprising
CC cancer-specific antigen or a nucleic acid encoding the protein. The
CC present sequence is lysosomal membrane protein, CD63 cytoplasmic tail
CC used in the chimeric protein of the invention
XX
SQ Sequence 10 AA;
Query Match 100.0%; Score 49; Length 10;
Best Local Similarity 100.0%;
Matches 10; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KSIRSGYEVM 10
||||||||||
Db 1 KSIRSGYEVM 10
Double Patenting
15. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 12-14, 19, 23, 26 and 30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7, 10, 12, 15, 25, 57-68 of copending Application No. 17/413881 in view of Cashman (WO2020118458), Skrlj (2013), Walensky (US11952432) and August et al. (WO200280851).
Claims 1-2, 7, 10, 12, 15, 25, 57-68 of Application No. 17/413881 (the ‘881 Application) claim an anti-TDP-43 antibody binding to TDP-43 sequence DAGWGNL, wherein the anti-TDP-43 antibody comprises the same amino acid sequences of instant SEQ ID NOs: for HCDRs1-3 and LCDRs1-3 or VH and VL and wherein the anti-TDP-43 antibody includes single chain antibody (claim 10). The anti-TDP-43 antibody binding to TDP-43 sequence DAGWGNL, which comprises Trp68 or W68, and thus the anti-TDP-43 antibody recited in the ‘881 Application is an anti-Trp68-TDP-43 antibody, including anti-Trp68-TDP-43 scAb.
But the claims of the ‘881 Application do not recite DNA molecules encoding the anti-Trp68-TDP-43 scAb or with a specific orientation of the VH-linker-VL or VL-linker-VH or comprising a linker that is about 10-25 amino acids including (GGGGS)3 (SEQ ID NO:180), (GGGGS)4 (SEQ ID NO:181) or GSTGGGGSGKPGSGEGGGGS (SEQ ID NO:182) as in claim 14 or a lysosomal targeting sequence including SEQ ID NO:174 or cell-penetrating peptide as in claim 16.
While the claims of the ‘881 Application do not recite DNA molecules encoding the anti-Trp68-TDP-43 scAb or with a specific orientation of the VH-linker-VL or VL-linker-VH or comprising a linker that is about 10-25 amino acids including (GGGGS)3 (SEQ ID NO:180), (GGGGS)4 (SEQ ID NO:181) or GSTGGGGSGKPGSGEGGGGS (SEQ ID NO:182) as in claim 14 or a lysosomal targeting sequence including SEQ ID NO:174 or cell-penetrating peptide as in claim 16, Cashman, Skrlj and Walensky teach these limitations and provide motivation and an expectation of success in generation of DNA molecules encoding the anti-Trp68-TDP-43 scAb or with a specific orientation of the VH-linker-VL or VL-linker-VH or comprising a linker that is about 10-25 amino acids including (GGGGS)3 (SEQ ID NO:180), (GGGGS)4 (SEQ ID NO:181) or GSTGGGGSGKPGSGEGGGGS (SEQ ID NO:182) as in claim 14 or a lysosomal targeting sequence including SEQ ID NO:174 or cell-penetrating peptide as in claim 16 for the reasons set forth above.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known DNA molecules encoding the anti-Trp68-TDP-43 scAb or with a specific orientation of the VH-linker-VL or VL-linker-VH or comprising a linker that is about 10-25 amino acids including (GGGGS)3 (SEQ ID NO:180), (GGGGS)4 (SEQ ID NO:181) or GSTGGGGSGKPGSGEGGGGS (SEQ ID NO:182) or a lysosomal targeting sequence including SEQ ID NO:174 or cell-penetrating peptide and the known technique disclosed by Cashman, Skrlj and Walensky and August to the anti-TDP-43 antibody binding to TDP-43 sequence DAGWGNL, which comprises Trp68 or W6 recited in the claims of the ‘881 Application, and yield the predictable result of a DNA construct encoding anti-misTDP-43-W68 single chain antibody comprising the structure of VH-linker-VL or the structure of VL-linker-VH as in claims 12-13, and wherein the linker is about 10-25 amino acids including (GGGGS)3 (SEQ ID NO:180), (GGGGS)4 (SEQ ID NO:181) or GSTGGGGSGKPGSGEGGGGS (SEQ ID NO:182) as in claim 14 or lysosomal targeting sequence having the amino acid sequence of SEQ ID NO:174 or cell-penetrating peptide as in claim 16.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
SEQ ID NO:100
US-17-413-881-100
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 100, US/17413881
Publication No. US20220056118A1
GENERAL INFORMATION
APPLICANT: The University of British Columbia
APPLICANT: ProMIS Neurosciences, Inc.
TITLE OF INVENTION: ANTIBODIES TO MISFOLDED TDP-43 AND METHODS OF USE
FILE REFERENCE: 27108-P54811PC00
CURRENT APPLICATION NUMBER: US/17/413,881
CURRENT FILING DATE: 2021-06-14
PRIOR APPLICATION NUMBER: 62/779,904
PRIOR FILING DATE: 2018-12-14
PRIOR APPLICATION NUMBER: 62/923,789
PRIOR FILING DATE: 2019-10-21
NUMBER OF SEQ ID NOS: 149
SEQ ID NO 100
LENGTH: 118
TYPE: PRT
ORGANISM: Oryctolagus cuniculus
Query Match 100.0%; Score 628; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QEQLEESGGDLVKPEGSLTLTCTASGFSFSSNYVMCWVRQAPGKGLEWVACIWFAGIVDT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QEQLEESGGDLVKPEGSLTLTCTASGFSFSSNYVMCWVRQAPGKGLEWVACIWFAGIVDT 60
Qy 61 TYYATWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARNPVGSVNLWGQGTLVTVS 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TYYATWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARNPVGSVNLWGQGTLVTVS 118
US-17-413-881-118
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 118, US/17413881
Publication No. US20220056118A1
GENERAL INFORMATION
APPLICANT: The University of British Columbia
APPLICANT: ProMIS Neurosciences, Inc.
TITLE OF INVENTION: ANTIBODIES TO MISFOLDED TDP-43 AND METHODS OF USE
FILE REFERENCE: 27108-P54811PC00
CURRENT APPLICATION NUMBER: US/17/413,881
CURRENT FILING DATE: 2021-06-14
PRIOR APPLICATION NUMBER: 62/779,904
PRIOR FILING DATE: 2018-12-14
PRIOR APPLICATION NUMBER: 62/923,789
PRIOR FILING DATE: 2019-10-21
NUMBER OF SEQ ID NOS: 149
SEQ ID NO 118
LENGTH: 118
TYPE: PRT
ORGANISM: Oryctolagus cuniculus
Query Match 90.6%; Score 569; Length 118;
Best Local Similarity 89.8%;
Matches 106; Conservative 5; Mismatches 7; Indels 0; Gaps 0;
Qy 1 QEQLEESGGDLVKPEGSLTLTCTASGFSFSSNYVMCWVRQAPGKGLEWVACIWFAGIVDT 60
|||||||||||| | |:||||| ||||||:||||||||||||||||||:||||||| |
Db 1 QEQLEESGGDLVTPGGTLTLTCKASGFSFNSNYVMCWVRQAPGKGLEWIACIWFAGSGDV 60
Qy 61 TYYATWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARNPVGSVNLWGQGTLVTVS 118
|||:||||||||||||||||||||||||||||||:||||||||||||||||||||||
Db 61 IYYASWAKGRFTISKTSSTTVTLQMTSLTAADTATHFCARNPVGSVNLWGQGTLVTVS 118
SEQ ID NO:101
US-17-413-881-101
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 101, US/17413881
Publication No. US20220056118A1
GENERAL INFORMATION
APPLICANT: The University of British Columbia
APPLICANT: ProMIS Neurosciences, Inc.
TITLE OF INVENTION: ANTIBODIES TO MISFOLDED TDP-43 AND METHODS OF USE
FILE REFERENCE: 27108-P54811PC00
CURRENT APPLICATION NUMBER: US/17/413,881
CURRENT FILING DATE: 2021-06-14
PRIOR APPLICATION NUMBER: 62/779,904
PRIOR FILING DATE: 2018-12-14
PRIOR APPLICATION NUMBER: 62/923,789
PRIOR FILING DATE: 2019-10-21
NUMBER OF SEQ ID NOS: 149
SEQ ID NO 101
LENGTH: 110
TYPE: PRT
ORGANISM: Oryctolagus cuniculus
Query Match 100.0%; Score 588; Length 110;
Best Local Similarity 100.0%;
Matches 110; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 VMTQTPSSKSVPVGGSVTINCQASESVYSNNRLSWYQQKPGQPPKLLIYYASTLESGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 VMTQTPSSKSVPVGGSVTINCQASESVYSNNRLSWYQQKPGQPPKLLIYYASTLESGVPS 60
Qy 61 RFKGSGFGTHFTLTISGAQCDDAATYYCAGWRGARTDGVDFGGGTEVVVK 110
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFKGSGFGTHFTLTISGAQCDDAATYYCAGWRGARTDGVDFGGGTEVVVK 110
US-17-413-881-119
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 119, US/17413881
Publication No. US20220056118A1
GENERAL INFORMATION
APPLICANT: The University of British Columbia
APPLICANT: ProMIS Neurosciences, Inc.
TITLE OF INVENTION: ANTIBODIES TO MISFOLDED TDP-43 AND METHODS OF USE
FILE REFERENCE: 27108-P54811PC00
CURRENT APPLICATION NUMBER: US/17/413,881
CURRENT FILING DATE: 2021-06-14
PRIOR APPLICATION NUMBER: 62/779,904
PRIOR FILING DATE: 2018-12-14
PRIOR APPLICATION NUMBER: 62/923,789
PRIOR FILING DATE: 2019-10-21
NUMBER OF SEQ ID NOS: 149
SEQ ID NO 119
LENGTH: 110
TYPE: PRT
ORGANISM: Oryctolagus cuniculus
Query Match 92.2%; Score 542; Length 110;
Best Local Similarity 91.8%;
Matches 101; Conservative 3; Mismatches 6; Indels 0; Gaps 0;
Qy 1 VMTQTPSSKSVPVGGSVTINCQASESVYSNNRLSWYQQKPGQPPKLLIYYASTLESGVPS 60
|||||||||||||||:|||||||||||| ||||||:|||||||||||||||||| |||||
Db 1 VMTQTPSSKSVPVGGTVTINCQASESVYINNRLSWFQQKPGQPPKLLIYYASTLASGVPS 60
Qy 61 RFKGSGFGTHFTLTISGAQCDDAATYYCAGWRGARTDGVDFGGGTEVVVK 110
|||||| || ||||||| |||||||||||||||| |||:|||||||||||
Db 61 RFKGSGSGTQFTLTISGVQCDDAATYYCAGWRGATTDGIDFGGGTEVVVK 110
Conclusion
16. NO CLAIM IS ALLOWED.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached on Monday-Thursday, 7:00am-5:00pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached on 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Chang-Yu Wang
November 27, 2025
/CHANG-YU WANG/Primary Examiner, Art Unit 1675