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 .
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Specifically, no sequence identification has been provided for the sequence presented on p. 91, line 33 of the amended specification filed on 12/08/2025.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
DETAILED ACTION
Status of Application/Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-7,16, 22-23 and 25), SEQ IDs: 20, 21, 164, 23-25 for HCDRs1-3 and LCDRs1-3 and SEQ ID NOs:186 and 160 for VH and VL in the reply filed on December 08, 2025 is acknowledged.
Claims 8, 15, 17 and 20-21 are canceled. Claims 1-7, 8-14, 16, 18-19 and 20-25 are pending in this application. Claims 9-14, 18-19 and 24 are withdrawn without traverse (filed 12/08/2025) from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 08, 2025.
Claims 1-7,16, 22-23 and 25 are under examination with respect to SEQ IDs: 20, 21, 164, 23-25 for HCDRs1-3 and LCDRs1-3 and SEQ ID NOs:186 and 160 for VH and VL 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 spelling “humanized” recited on p. 5-9 and across the whole document of the specification filed 12/08/2025 is incorrect. Appropriate correction is required.
Duplicate Claims
Applicant is advised that should claim 2 be found allowable, claim 7 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Objections
Claims 1-7, and 25 objected to because of the following informalities: The spelling of “humanized” recited in claims 1-7 and 25 is incorrect. Appropriate correction is required.
Claims 9-14, 18-19 and 24 are objected to because of the following informalities: the status of the claims 9-14, 18-19 and 24 is incorrect because these claims are withdrawn from consideration. Appropriate correction is required.
See MPEP 714 & 37 CFR 1.121.
“In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).”
Improper Markush Grouping
10. Claims 3-6 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 humanized anti-human 2N4R antibodies comprising different SEQ ID NOs: and variants for CDRs1-3 recited in claim 3, the Markush grouping of different humanized anti-human 2N4R antibodies VH4_H04, VH_H02……VH4_H14/L2 comprising different SEQ ID NOs: for HCDR1-3 and LCDR1-3 recited in claim 4 and the Markush grouping of different clone VH4_H04….. Clone VH4VK3(D) recited in claims 5-6 comprising different SEQ ID NOs: for VH and VL are 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 humanized anti-human 2N4R antibodies has a different chemical structure because it comprises different amino acid sequences for HCDRs1-3 and LCDRs1-3 or VH and VL. Each antibody has a different binding activity to epitopes. Thus, the antibodies do not share a single structural similarity or biological activity. Accordingly, while the different antibodies are asserted to have the property of being correlated with a neurological or movement disorder or an altered susceptibility thereto, they do not share a single structural similarity essential to this 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
11. 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 3-6 and 22-23 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 22-23 are indefinite because:
i. Claims 3-5 recite the limitation "the antigen-binding site” in line 2 of the claims. There is insufficient antecedent basis for this limitation in the claim.
ii. Claims 5-6 recite the limitation "the VH and/or VL” in lines 2-3 of the claims. There is insufficient antecedent basis for this limitation in the claim.
iii. Claim 22 recites the limitation "said isolated recombinant peptide binding molecule" in lines 3-5, 7-8 of the claim. There is insufficient antecedent basis for this limitation in the claim.
iv. Regarding claim 22, the limitation "(e.g. microplate well)" recited in line 6 of the claim render the claim indefinite because it is unclear whether the limitation(s) following the limitation “e.g.” are part of the claimed invention. See MPEP § 2173.05(d).
v. The rest of claims are indefinite as depending from an indefinite claim.
Claim Rejections - 35 USC § 112
12. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-3, 5, 7,16, 22-23 and 25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
Claims 1-3, 5, 7,16, 22-23 and 25 encompass a genus of humanized antibodies or antigen-binding fragments thereof comprising a genus of sequences that specifically binding to an epitope form by residues of the amino acid sequence 369-381 (SEQ ID NO:1) or aa 373-379 (SEQ ID NO:150) of human 2N4R (amino acids 1-441) tau (SEQ ID NO:2). Claim 3 encompasses a genus of humanized antibodies or antigen-binding fragments thereof comprising CDRs or variants selected from recited SEQ ID NOs: in claim 3. Claim 5 encompasses encompass a genus of humanized antibodies or antigen-binding fragments thereof comprising at least 90%...99% identity to recited SEQ ID NOs: for VH and VL.
In deciding 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, Applicant is in possession of humanized antibody clones VH1VK1….VH5Vk4 listed on p. 65-66, Table 10 or p. 81-83, Tables 15-17 in the specification or recited in instant claims 4 and 6 that are capable of binding to aa 369-381 (SEQ ID NO:1) of human 2N4R tau (1-441 of SEQ ID NO:2). However, Applicant is not in possession of other structurally and functionally undefined antibodies binding to aa 369-381 (SEQ ID NO:1) or aa 373-379 (SEQ ID NO:150) of human 2N4R tau (1-441 of SEQ ID NO:2) recited in claims 1-2 and 7 or variant antibodies having recited SEQ ID NOs: or variants thereof for CDRs1-3 recited in claim 3 or variants with at least 90%..99% identity to recited SEQ ID NOs: for VH and VL recited in claim 5.
The specification fails to provide sufficient description as to what structures or sequences for the claimed humanized antibodies recited in claims 1-2 and 7 or their corresponding heavy chain, light chain, variable regions, or H/LCDRs1-3 are in order to generate antibodies with the claimed binding ability or features, and what sequences can or cannot be changed in variant antibodies recited in claims 3 and 5 in order to have the claimed binding ability or features.
As an initial matter, Applicant has provided no structures or sequences sufficiently detailed to show that he/she was in possession of the claimed invention as a whole. There was also no known or disclosed correlation between the required function (i.e. binding to aa 369-381 (SEQ ID NO:1) of human 2N4R tau (1-441 of SEQ ID NO:2 or aa 373-379 (SEQ ID NO:150 of human 2N4R tau (aa 1-441 of SEQ ID NO:2)) and any particular structure or sequence for the antibodies recited in claims 1-2 and 7.
Applicant has not disclosed sufficient species for the broad genus of antibodies. The specification only humanized antibody clones VH1VK1….VH5Vk4 listed on p. 65-66, Table 10 or p. 81-83, Tables 15-17 in the specification. However, the specification fails to demonstrate that Applicant is in possession of the genus of the claimed antibodies as recited in claims 1-2 and 7 because the claims also encompass other antibodies with structurally and functionally undefined sequences.
In light of Amgen, Inc. v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), describing a “fully characterized antigen” for an antibody is no longer adequate on its own to demonstrate possession of the antibody. Based on MPEP§2161.01 and 2163, the USPTO guidance regarding written description requirement of 35 U.S.C.§C112 (a), specifically concerning the written description requirement for claims drawn to antibodies and Federal Circuit decisions, when an antibody is claimed, 35USC112(a) requires adequate written description of the antibody itself. See Amgen 872 F.3d at 1378-79.
The court of the Federal Circuit also stressed that the “newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. See Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir.2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional.
Furthermore, the Fed. Cir.’s decision in Amgen confirmed that post-filing disclosures may be informative in establishing the size of the claimed genus. In this case, there are numerous disclosures of novel antibodies that were published after applicants’ filing date and are not fairly described in it. For example, Zhao et al. (WO2025075789), and the sequences disclosed by Zhao are not taught or suggested by the instant specification, and the instant application provides no structure at all for comparison. Except the antibodies shown in Table 10, the specification’s general reference to humanized antibodies “binding to aa 369-381 (SEQ ID NO:1) of human 2N4R tau (1-441 of SEQ ID NO:2 or aa 373-379 (SEQ ID NO:150 of human 2N4R tau (aa 1-441 of SEQ ID NO:2)” recited in claims 1-2 and 7 does not clearly suggest any particular sequences that can be used in order to result in the claimed antibodies or the claimed features. As such, he/she cannot possibly have possessed the entire genus.
In addition, based on Applicant’s own admission on p. 63 of the specification, VH6 clones do not bind to 2N4R tau because it includes a mutation within VHCDR1, A35S (see p. 63, figure 7).
The specification fails to provide sufficient description as to what sequences can or cannot be changed in variant antibodies recited in claims 3 and 5 in order to have the claimed binding ability or features. MacCallum et al. (J. Mol. Biol.,1996; 262: 732-745) teaches that although CDR3 of the heavy and light chain dominate, a number of residues outside the standard CDR definitions make antigen contacts (see p. 733, right col) and non-contacting residues within the CDRs coincide with residues as important in defining canonical backbone conformations (see page 735, left col.). Pascalis et al. (The Journal of Immunology, 2002; 169: 3076-3084) teaches that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page 3079, right col.) and that although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs (see page 3080, left col.). The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site because although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process (page 199, left col.) and this is demonstrated in this work by using all CDRs except L2 and additionally using a framework residue located just before the H3 (see page 202, left col.; Casset et al., BBRC, 2003; 307: 198-205). Vajdos et al. (J. Mol. Biol. 2002; 320: 415-428) also teaches that antigen binding is primarily mediated by the CDRs more highly conserved framework segments which connect the CDRs are mainly involved in supporting the CDR loop conformations and in some cases framework residues also contact antigen (page 416, left col.). Holm et al. (Mol. Immunol., 2007; 44: 1075-1084) teaches that although residues in the CDR3 of the heavy chain were involved in antigen binding, unexpectedly a residue in CDR2 of the light chain was also involved (abstract). Chen et al. (J. Mol. Bio., 1999; 293: 865-881) teaches that the antigen binding site is almost entirely composed of residues from heavy chain CDRs, CDR-H1, H2, H3 (page 866). Wu et al. (J. Mol. Biol., 1999; 294:151-162) teaches that it is difficult to predict which framework residues serve a critical role in maintaining affinity and specificity due in part to the large conformational change in antibodies that accompany antigen binding (page 152 left col.) but certain residues have been identified as important for maintaining conformation.
It is also known in the art that a single amino acid change can abolish the binding ability of a molecule. 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.
The specification fails to teach what specific structures/amino acid sequences can or cannot be changed or included in order to preserve the claimed binding ability or features. There is no description of the conserved regions which are critical to the function of the claimed genus. 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 antibodies containing structurally and functionally undefined sequences to the function of the antibodies recited in the claims. Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to isolate and identify what other humanized antibodies containing structurally and functionally undefined sequences or variants might be. Since the common characteristics/features of other antibodies containing structurally and functionally undefined sequences 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 humanized antibodies or variants thereof.
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 humanized antibodies or variants thereof, 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 and Centocor v. Abbott, 636 F.3d1341 (Fed. Cir. 2011) and AbbVie v. Janssen, 759 F.3d 1285 (Fed. Cir.2014). One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483.
Therefore, the claimed humanized antibodies 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.
13. 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
14. 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, 7,16 and 25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sigurdsson et al. (US2008/0050383, published Feb 28, 2008, priority Mar 29, 2006).
Claims 1-7,16 and 25 are drawn to an humanized antibody or antigen-binding fragment thereof, comprising a sequence that binds specifically to an epitope form by residues of the amino acid sequence 369-381 (SEQ ID NO:1).
Sigurdsson et al. (US2008/0050383) teach a humanized antibody or antigen-binding fragment thereof specifically binding to a human tau epitope (aa. 360-390: SEQ ID NO:18), wherein the human epitope is 100% identical to aa 369-381 (instant SEQ ID NO:1) recited in claim 1 or 100% identical to instant SEQ ID NO:150 recited in claim 2 (see the sequence alignment; para. [0036], p. 12, Table SEQ ID NO:18; para. [0049]; [0059]). Sigurdsson teaches a composition comprising the claimed antibody or antigen-binding fragment thereof and a pharmaceutically acceptable diluent as in claim 16 (see para. [0053]-[0054]; [0057]; [0065]-[0072]). The humanized antibody disclosed by Sigurdsson binding to an epitope that is 100% identical to aa 360-390 (SEQ ID NO:1) or aa 373-379 (SEQ ID NO:150) and thus comprises K375, T377 and R379 or T373,K375, T377 and R379 recited in claim 25. Thus, claims 1-2, 7,16 and 25 are anticipated by Sigurdsson et al. (US2008/0050383).
The sequence search results disclose as follows:
SEQ ID NO:150
AQY86884
(NOTE: this sequence has 8 duplicates in the database searched)
ID AQY86884 standard; peptide; 31 AA.
XX
AC AQY86884;
XX
DT 01-MAY-2008 (first entry)
XX
DE Human tau (360-390) immunogenic epitope, SEQ ID 18.
XX
KW immunotherapy; therapeutic; prophylactic to disease; alzheimers disease;
KW neuroprotective; nootropic; tau; epitope.
XX
OS Homo sapiens.
XX
FH Key Location/Qualifiers
FT Modified-site 31
FT /note= "C terminal amide"
XX
CC PN US2008050383-A1.
XX
CC PD 28-FEB-2008.
XX
CC PF 29-MAR-2007; 2007US-00693375.
XX
PR 29-MAR-2006; 2006US-0787051P.
XX
CC PA (UYNY ) UNIV NEW YORK STATE.
XX
CC PI Sigurdsson E, Asuni A;
XX
DR WPI; 2008-C62536/19.
XX
CC PT Treating or preventing Alzheimer's disease or other tauopathies in a
CC PT subject comprises administering a tau protein, its immunogenic epitopes,
CC PT or antibodies recognizing the tau protein or its immunogenic epitopes.
XX
CC PS Claim 31; SEQ ID NO 18; 65pp; English.
XX
CC The present invention relates to a method of immunotherapy for clearing
CC aggregates from the brain of a subject and slowing progression of a
CC tangle-related behavioral phenotype in a subject. The method of the
CC invention is useful for treating or preventing Alzheimer's disease or
CC other tauopathies in a subject by administering a tau protein, its
CC immunogenic epitopes, or antibodies recognizing the tau protein or its
CC immunogenic epitopes. The present sequence represents an immunogenic
CC epitope of tau protein.
XX
SQ Sequence 31 AA;
Query Match 100.0%; Score 7; Length 31;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 THKLTFR 7
|||||||
Db 14 THKLTFR 20
Claim Rejections - 35 USC § 103
15. 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 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Sigurdsson et al. (US2008/0050383) in view of Wadia et al. (US11472869, issued Oct 18, 2022, priority Jun 26, 2014) and Wasserman et al. (US20200132683, published Apr 30, 2020, priority Oct 25, 2018).
Sigurdsson is set forth above but fails to teach a diagnostic kit comprising the claimed antibody or antigen-binding fragment thereof and a reagent for detection or further comprising control standards and/or specimen diluent and/or washing buffer as in claims 22-23.
Wadia et al. (US11472869) teaches a diagnostic kit comprising an anti-Tau 2N4R antibody or antigen-binding fragment thereof and reagents capable of detecting an immunological antigen-antibody complex, or on a solid support or by ELISA or alternative immunoassay method: immunohistochemistry or western blot or in vivo imaging or further comprising control standards and/or specimen diluent and/or washing buffer as in claims 22-23 (see col. 23, line 35-col. 24, line 32).
Wasserman et al. (US20200132683) teaches a diagnostic kit comprising an anti-Tau antibody and reagents capable of detecting an immunological antigen-antibody complex, or on a solid support comprising a high flow nitrocellulose membrane configured for lateral flow in a first direction via capillary action, or further comprising control standards and/or specimen diluent and/or washing buffer as in claims 22-23 (para. [0031]; [0081]; [0086]-[0093], claims 1-6).
A person of ordinary skill in the art would have recognized that selecting and applying the known diagnostic kit comprising an anti-Tau 2N4R antibody including the claimed humanized antibody and reagents for detection by ELISA or alternative immunoassay or lateral flow and control standards and specimen diluent and/or washing buffer and the known technique disclosed by Wadia and Wasserman to the Sigurdsson’s humanized antibody and composition would have yielded the predictable result of a diagnostic kit comprising the claimed humanized antibody and reagents for detection by ELISA, alternative immunoassay or lateral flow, and resulted in an improved product for diagnosis.
Using the known technique and the known diagnostic kit comprising an anti-Tau 2N4R antibody including the claimed humanized antibody and reagents for detection by ELISA or alternative immunoassay or lateral flow and control standards and specimen diluent and/or washing buffer in the Sigurdsson’s composition comprising the claimed humanized antibody would generate the known diagnostic kit and expand application of the Sigurdsson’s composition comprising the claimed humanized antibody in pharmaceutical purposes for treatment and diagnosis, and would increase patient’s satisfaction with treatment and diagnosis using the humanized anti-Tau 2N4R antibody because the diagnostic kit comprising the claimed reagents for detection by ELISA, alternative immunoassay or lateral flow is known and routine practice in the art.
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 diagnostic kit comprising an anti-Tau 2N4R antibody including the claimed humanized antibody and reagents for detection by ELISA or alternative immunoassay or lateral flow and control standards and specimen diluent and/or washing buffer and the known technique disclosed by Wadia and Wasserman to the Sigurdsson’s composition and yield the predictable result of the claimed diagnostic kit comprising the claimed humanized antibody and reagents for detection by ELISA or alternative immunoassay or lateral flow and control standards and specimen diluent and/or washing buffer.
Double Patenting
16. 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 1-3, 5, 7,16, 22-23 and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8-12, 14-21, 25-31 of copending Application No. 17623577 (the ‘577 Application) in view of Sigurdsson et al. (US2008/0050383).
The ‘577 Application claims an antibody binding to aa 373-379 (SEQ ID NO:150) and a diagnostic kit comprising the claimed antibody.
The claims of the ‘577 Application do not recite “humanized antibody” recited in claim 1.
While the claims of the ‘577 Application do not recite “humanized antibody”, Sigurdsson (US2008/0050383) teaches this limitation and provides motivation and an expectation of success for the reason set forth above under the 102 rejection. 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 humanized antibody or antigen-binding fragment thereof specifically binding to a human tau epitope aa 369-381 (instant SEQ ID NO:1) or aa 373-379 (instant SEQ ID NO:150) and the known technique of humanizing an antibody disclosed by Sigurdsson to the claims of the ‘577 Application, and yield the predictable result of the claimed humanized antibody or antigen-binding fragment thereof specifically binding to a human tau epitope aa 369-381 (instant SEQ ID NO:1) or aa 373-379 (instant SEQ ID NO:150).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
SEQ ID NO:1
US-17-623-577A-1
Sequence 1, US/17623577A
Publication No. US20230192826A1
GENERAL INFORMATION
APPLICANT: Gen2 Neuroscience Limited
TITLE OF INVENTION: Tau Epitope and Binding Molecules
FILE REFERENCE: GEN2BR001WO1
CURRENT APPLICATION NUMBER: US/17/623,577A
CURRENT FILING DATE: 2022-12-28
PRIOR APPLICATION NUMBER: GB1909393.9
PRIOR FILING DATE: 2019-06-28
NUMBER OF SEQ ID NOS: 150
SEQ ID NO 1
LENGTH: 13
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Peptide sequence corresponding to amino acids 369-381 of 2N4R tau
1-441
Query Match 100.0%; Score 13; Length 13;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KKEITHKLTFREN 13
|||||||||||||
Db 1 KKEITHKLTFREN 13
aa 369-381 of SEQ ID NO:2
US-17-623-577A-13
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 13, US/17623577A
Publication No. US20230192826A1
GENERAL INFORMATION
APPLICANT: Gen2 Neuroscience Limited
TITLE OF INVENTION: Tau Epitope and Binding Molecules
FILE REFERENCE: GEN2BR001WO1
CURRENT APPLICATION NUMBER: US/17/623,577A
CURRENT FILING DATE: 2022-12-28
PRIOR APPLICATION NUMBER: GB1909393.9
PRIOR FILING DATE: 2019-06-28
NUMBER OF SEQ ID NOS: 150
SEQ ID NO 13
LENGTH: 14
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Peptide sequence corresponding to amino acids 369-381 of 2N4R tau 1-441 with N-terminal cysteine
Query Match 100.0%; Score 68; Length 14;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KKIETHKLTFREN 13
|||||||||||||
Db 2 KKIETHKLTFREN 14
SEQ ID NO:186
US-17-623-577A-118
(NOTE: this sequence has 2 duplicates in the database searched)
Sequence 118, US/17623577A
Publication No. US20230192826A1
GENERAL INFORMATION
APPLICANT: Gen2 Neuroscience Limited
TITLE OF INVENTION: Tau Epitope and Binding Molecules
FILE REFERENCE: GEN2BR001WO1
CURRENT APPLICATION NUMBER: US/17/623,577A
CURRENT FILING DATE: 2022-12-28
PRIOR APPLICATION NUMBER: GB1909393.9
PRIOR FILING DATE: 2019-06-28
NUMBER OF SEQ ID NOS: 150
SEQ ID NO 118
LENGTH: 135
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Clone 2 VH sequence
Query Match 80.1%; Score 487; Length 135;
Best Local Similarity 83.0%;
Matches 93; Conservative 7; Mismatches 10; Indels 2; Gaps 1;
Qy 4 LQESGPGLVKPSETLSLTCTVSGIDLSSYAMAWVRQAPGKGLEWIGCIDRRGGTFYASWV 63
::||| || | |:||||||||||||||||||||||||||||||||||||||||||||
Db 9 VEESGGRLVTPGTPLTLTCTVSGIDLSSYAMAWVRQAPGKGLEWIGCIDRRGGTFYASWV 68
Qy 64 KGRFTISKDTSKTTVDLQMTSLTAEDTATYFCARDAGSFHPWGQGTLVTVSS 115
|||||||| : |||||:||||| |||||||||||:|:| ||| ||||||||
Db 69 KGRFTISK--TSTTVDLKMTSLTTEDTATYFCARDSGAFDPWGPGTLVTVSS 118
Conclusion
17. NO CLAIM IS ALLOWED.
18. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
WO2018152359 teaches an antibody against human tau epitope (SEQ ID NO:136), which is 100% identical to instant SEQ ID NO:150 (see the sequence alignment).
SEQ ID NO:150
BFP52127
(NOTE: this sequence has 5 duplicates in the database searched)
ID BFP52127 standard; peptide; 15 AA.
XX
AC BFP52127;
XX
DT 04-OCT-2018 (first entry)
XX
DE Human Tau epitope peptide, SEQ ID 136.
XX
KW MAPT protein; Microtubule-associated protein; Tau protein;
KW alzheimers disease; antibody production; antibody therapy; cell line;
KW epitope; hybridoma; neurodegenerative disease; neuroprotective;
KW prophylactic to disease; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2018152359-A1.
XX
CC PD 23-AUG-2018.
XX
CC PF 15-FEB-2018; 2018WO-US018415.
XX
PR 17-FEB-2017; 2017US-0460642P.
PR 08-NOV-2017; 2017US-0583400P.
XX
CC PA (DENA-) DENALI THERAPEUTICS INC.
XX
CC PI Chen X, Dennis MS, Kane LA, Kim DJ, Lewcock JW, Poda S;
CC PI Rakhit R, Shukla R, Silverman AP;
XX
DR WPI; 2018-658110/60.
XX
CC PT Isolated antibody or antigen-binding portion used in bispecific antibody,
CC PT and vector, which is used in pharmaceutical composition for treating
CC PT neurodegenerative disease, is one, which specifically binds to human Tau
CC PT protein.
XX
CC PS Example 1; SEQ ID NO 136; 339pp; English.
XX
CC The present invention relates to a novel isolated antibody or its antigen
CC -binding portion, useful in a pharmaceutical composition for treating
CC neurodegenerative disease. The isolated antibody or its antigen-binding
CC portion specifically binds to a human Tau protein and recognizes an
CC epitope within residues 111-125 of SEQ ID NO: 1 (see BFP51992). The
CC invention also provides: a hybridoma cell line that produces antibody
CC clone 17G2.A1, 19F7.C9, or 24D2.B2; a method for preventing or reducing
CC pathological Tau seeding and/or spreading in a brain of subject; and a
CC method for treating a neurodegenerative disease. The neurodegenerative
CC disease is tauopathy or neurodegenerative tauopathy, and
CC neurodegenerative tauopathy is selected from Alzheimer's disease, primary
CC age-related tauopathy, progressive supranuclear palsy, frontotemporal
CC dementia, frontotemporal dementia with parkinsonism linked to chromosome
CC 17, argyrophilic grain dementia, amyotrophic lateral
CC sclerosis/parkinsonism-dementia complex of Guam, corticobasal
CC degeneration, chronic traumatic encephalopathy, Creutzfeldt-Jakob
CC disease, dementia pugilistica, diffuse neurofibrillary tangles with
CC calcification, Down's syndrome, familial British dementia, familial
CC Danish dementia, Gerstmann-Straussler-Scheinker disease, globular glial
CC tauopathy, Guadeloupean parkinsonism with dementia, Guadelopean PSP,
CC Hallevorden-Spatz disease, inclusion-body myositis, multiple system
CC atrophy, myotonic dystrophy, neurofibrillary tangle-predominant dementia,
CC Niemann-Pick disease type C, pallido-ponto-nigral degeneration,
CC Parkinson's disease, Pick's disease, postencephalitic parkinsonism, prion
CC protein cerebral amyloid angiopathy, progressive subcortical gliosis,
CC subacute sclerosing panencephalitis, Huntington's disease, and tangle
CC only dementia, particularly neurodegenerative tauopathy is Alzheimer's
CC disease. The present sequence is a human Tau epitope peptide, which is
CC used as a target for the antibody of the invention.
XX
SQ Sequence 15 AA;
Query Match 100.0%; Score 7; Length 15;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 THKLTFR 7
|||||||
Db 8 THKLTFR 14
WO2018226590 teaches an antibody against human tau epitope (SEQ ID NO:136), which is 100% identical to instant SEQ ID NO:150 (see the sequence alignment).
SEQ ID NO:150
BFW97156
ID BFW97156 standard; peptide; 16 AA.
XX
AC BFW97156;
XX
DT 24-JAN-2019 (first entry)
XX
DE Human tau epitope peptide (residues 369-384) SEQ: 47.
XX
KW MAPT protein; Tau protein; alzheimers disease; antiparkinsonian;
KW biomarker; diagnostic test; epitope; growth-disorder-gen.; immunotherapy;
KW lewy body dementia; microtubule-associated protein Tau;
KW motor neurone disease; neurological disease; neuroprotective; nootropic;
KW parkinsons disease; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2018226590-A1.
XX
CC PD 13-DEC-2018.
XX
CC PF 04-JUN-2018; 2018WO-US035870.
XX
PR 05-JUN-2017; 2017US-0515429P.
PR 12-JUN-2017; 2017US-0518285P.
PR 14-JUN-2017; 2017US-0519558P.
PR 20-JUN-2017; 2017US-0522643P.
PR 04-OCT-2017; 2017US-0568099P.
PR 15-NOV-2017; 2017US-0586597P.
PR 01-MAR-2018; 2018US-0637303P.
XX
CC PA (UYCO ) UNIV COLUMBIA NEW YORK.
CC PA (LJOL-) LA JOLLA INST ALLERGY & IMMUNOLOGY.
CC PA (REME-) RES FOUND MENTAL HYGIENE INC.
CC PA (SULZ/) SULZER D.
CC PA (SETT/) SETTE A.
CC PA (ARLE/) ARLEHAMN C L.
CC PA (PHAM/) PHAM J.
CC PA (PETE/) PETERS B.
XX
CC PI Sulzer D, Sette A, Arlehamn CL, Pham J, Peters B;
XX
DR WPI; 2018-A1071X/02.
XX
CC PT Assessing whether subject is at risk of developing, or for diagnosing or
CC PT confirming whether subject is afflicted with alpha-synucieinopathy,
CC PT tauopathy, parkinson's disease, amyotrophic lateral sclerosis, lewy Body
CC PT dementia, or alzheime's.
XX
CC PS Claim 5; SEQ ID NO 47; 244pp; English.
XX
CC The present invention relates to a novel method for assessing whether a
CC subject is at risk of developing, or for diagnosing neurological
CC disorders. The method comprises: (1) obtaining leukocytes from the
CC subject; (2) contacting the leukocytes with an epitope peptide; and (3)
CC determining whether the leukocytes have increased activation after
CC contact with the epitope peptide. The epitope peptide is selected from
CC the group consisting of: (i) SEQ ID NOs: 1-55 (see BFW97110-BFW97164) or
CC SEQ ID NOs: 240-376 (see BFW97349-BFW97485), derived from tau protein
CC (microtubule-associated protein Tau or MAPT); (ii) SEQ ID NOs: 377-521
CC (see BFW97486-BFW97630), derived from alpha-synuclein protein; and SEQ ID
CC NOs: 56-239 (see BFW97165-BFW97348), derived from TDP43 protein. The
CC invention claims: (a) a method for treating a subject afflicted with
CC alpha-synucleinopathy, tauopathy, Parkinson's disease (PD), amyotrophic
CC lateral sclerosis (ALS), lewy body dementia (LBD), or Alzheimer's disease
CC (AD); (b) a method for assessing whether a test compound comprises an
CC epitope peptide to which leukocytes of a subject suffering from a
CC neurological disorder are responsive; and (c) a pharmaceutical
CC composition useful for treating the above-mentioned diseases, comprising
CC a protein containing the epitope peptide and a pharmaceutically
CC acceptable carrier.
XX
SQ Sequence 16 AA;
Query Match 100.0%; Score 7; Length 16;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 THKLTFR 7
|||||||
Db 5 THKLTFR 11
WO2012162179 teaches an antibody against human tau epitope (SEQ ID NO:35), which is 100% identical to instant SEQ ID NO:150 (see the sequence alignment).
SEQ ID NO:150
BAH73843
(NOTE: this sequence has 1 duplicate in the database searched)
ID BAH73843 standard; protein; 15 AA.
XX
AC BAH73843;
XX
DT 17-JAN-2013 (first entry)
XX
DE Tau protease cleaved human tau protein fragment, SEQ ID 35.
XX
KW Tau protein; alzheimers disease; amnesia; antibody therapy; dementia;
KW diagnostic test; drug discovery; neurodegenerative disease;
KW neurological disease; neuroprotective; nootropic; protein production;
KW protein therapy; recombinant protein; senile dementia; therapeutic;
KW traumatic brain injury; vulnerary.
XX
OS Homo sapiens.
XX
CC PN WO2012162179-A1.
XX
CC PD 29-NOV-2012.
XX
CC PF 18-MAY-2012; 2012WO-US038672.
XX
PR 20-MAY-2011; 2011US-0488493P.
PR 06-OCT-2011; 2011US-0544090P.
PR 12-DEC-2011; 2011US-0569558P.
XX
CC PA (OLIG-) OLIGOMERIX INC.
XX
CC PI Moe JG, Davidowitz EJ, Lopez P;
XX
DR WPI; 2012-Q76440/82.
XX
CC PT New isolated peptide or polypeptide comprising specific amino acid
CC PT sequences, useful for producing truncated tau protease or tau protease
CC PT variant, and identifying serine protease inhibitor.
XX
CC PS Example 7; SEQ ID NO 35; 147pp; English.
XX
CC The present invention relates to a novel isolated peptide or polypeptide,
CC useful for producing truncated tau protease or tau protease variant and
CC identifying serine protease inhibitor. The invention also provides: a tau
CC protease variant peptide or polypeptide comprising a mammalian tau
CC protease that has been substituted in at least one amino acid at a
CC position that corresponds to amino acid residues 5, 257, 260, 266, 272,
CC 273, 279, 280, 285, 296, 301, 303-305, 315, 317, 320, 332, 335-337, 342,
CC 352, 356, 363, 369, 389, 406 or 427 of SEQ ID NO: 6 (BAH73814); an
CC antibody or antigen binding fragment capable of binding to the isolated
CC peptide or polypeptide; an isolated polynucleotide encoding the peptide,
CC polypeptide or antibody; an expression vector comprising the isolated
CC polynucleotide; an isolated host cell transformed with the expression
CC vector; a composition comprising a pharmaceutically acceptable carrier
CC and (a) the peptide or polypeptide, (b) the antibody or antigen binding
CC fragment, (c) the isolated polynucleotide, (d) the expression vector, or
CC (e) the isolated host cell; a method (M1) for producing a truncated tau
CC protease or a tau protease variant by (i) culturing a population of
CC recombinant host cells comprising the encodes the peptide or polypeptide,
CC under the conditions of truncated or variant tau protease expression, and
CC (ii) recovering the truncated or variant tau protease from the population
CC of host cells or the culture medium; a method (M2) for identifying a
CC serine protease inhibitor; a recombinant serine protease prepared from
CC the method M1; and a recombinant tau 4R2N trimer protease fusion protein.
CC The composition of the invention is useful for treating, diagnosing,
CC amelioration of symptoms, or discovering a drug for tauopathy, neural
CC deficit, dementia, senility, age-related memory loss, traumatic brain
CC injury or Alzheimer's disease. The present sequence represents a tau
CC protease cleaved human tau protein fragment, which can be used for
CC identifying active fragments capable of demonstrating protease activity
CC in Alzheimer's disease. Note: The present sequence is also described as
CC SEQ ID NO: 35 in the sequence listing, but it is also described as SEQ ID
CC NO: 37 in page 87 and differs from the sequence described as SEQ ID NO:
CC 35 in page 87 (see BAH73841).
XX
SQ Sequence 15 AA;
Query Match 100.0%; Score 7; Length 15;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 THKLTFR 7
|||||||
Db 3 THKLTFR 9
WO2013041962 teaches an antibody against human tau epitope (SEQ ID NO:91), which is 100% identical to instant SEQ ID NO:150 (see the sequence alignment).
SEQ ID NO:150
BAM75444
ID BAM75444 standard; peptide; 30 AA.
XX
AC BAM75444;
XX
DT 23-MAY-2013 (first entry)
XX
DE Human tau 30-mer peptide immunogen tau 355-384, SEQ: 91.
XX
KW Tau protein; alzheimers disease; antibody production; antibody therapy;
KW antigen; cell line; cognitive disorder; diagnostic test;
KW immune stimulation; movement disorder; neurodegenerative disease;
KW neuroprotective; nootropic; prognosis; prophylactic to disease;
KW screening; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2013041962-A1.
XX
CC PD 28-MAR-2013.
XX
CC PF 14-SEP-2012; 2012WO-IB002246.
XX
PR 19-SEP-2011; 2011US-0536339P.
PR 30-MAY-2012; 2012US-0653115P.
XX
CC PA (AXON-) AXON NEUROSCIENCE SE.
XX
CC PI Kontsekovae E, Kovacech B, Novaek M, Zilka N;
XX
DR WPI; 2013-E32202/25.
XX
CC PT New isolated antibody, which is capable of displaying higher affinity for
CC PT pathological tau than the physiological tau, useful for diagnosing,
CC PT preventing or treating Alzheimer's disease or related tauopathies.
XX
CC PS Claim 59; SEQ ID NO 91; 350pp; English.
XX
CC The present invention relates to an isolated antibody that binds to one
CC or more tau epitopes. The isolated antibody (DC8E8) is used as a drug or
CC in the manufacture of a medicament for treatment of Alzheimer's disease
CC or related tauopathies. The invention also provides a method for a
CC prophylactic and therapeutic treatment of Alzheimer's disease and other
CC neurodegenerative tauopathies. The method entails the injection of
CC antibodies and/or peptide vaccines that elicits an immune response
CC directed to pathological tau proteins and tau deposits in the brains of
CC patients. The invention independently claims: (a) an isolated nucleic
CC acid encoding at least a binding domain or a variable region of an
CC immunoglobulin chain of the antibody; (b) an isolated vector comprising
CC the nucleic acid; (c) an isolated host cell comprising the isolated
CC nucleic acid ; (d) an isolated cell line expressing the isolated antibody
CC ; (e) a pharmaceutical composition comprising the antibody; (f) a method
CC for treating or preventing the progression of Alzheimer's disease or
CC related tauopathies in a subject, wherein the method is capable of
CC reducing motor impairment, improving motor function, reducing cognitive
CC impairment, improving cognitive function or a combination thereof; (g) a
CC method for diagnosing or screening the subject for the presence of
CC Alzheimer's disease or the related tauopathy; (h) a method for monitoring
CC the subject for the presence, progression, regression or stabilization of
CC Alzheimer's disease or related tauopathies in a subject; and (i) a method
CC for producing the antibody. The present sequence represents a human tau
CC 30-mer peptide immunogen carrying one therapeutic epitope which is
CC recognized by the antibody of the invention.
XX
SQ Sequence 30 AA;
Query Match 100.0%; Score 7; Length 30;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 THKLTFR 7
|||||||
Db 19 THKLTFR 25
WO2020260722 teaches an antibody against human tau epitope aa 369-381 of SEQ ID NO:1 (see the sequence alignment).
SEQ ID NO:1
BIU57633
(NOTE: this sequence has 1 duplicate in the database searched)
ID BIU57633 standard; peptide; 13 AA.
XX
AC BIU57633;
XX
DT 18-FEB-2021 (first entry)
XX
DE Human tau protein epitope (369-381), SEQ 1.
XX
KW 2N4R tau; Tau protein; alzheimers disease; antibody production;
KW antibody therapy; antimicrobial-gen.; antiparkinsonian; aphasia;
KW brain disease; cerebral amyloid angiopathy; cerebroprotective;
KW creutzfeldt jakob disease; diagnostic test; down syndrome; epitope;
KW frontotemporal dementia; genetic-disease-gen.;
KW gerstmann straussler scheinker disease; growth-disorder-gen.;
KW hallervorden-spatz syndrome; immune stimulation; immuno-diagnosis;
KW ischemic stroke; metabolic-gen.; motor neurone disease;
KW multi-infarct dementia; multiple system atrophy; muscular-gen.; myositis;
KW myotonic dystrophy; neuroprotective; niemann pick disease type c;
KW nootropic; parkinsons disease dementia; prophylactic to disease;
KW protein detection; stroke; therapeutic; traumatic brain injury;
KW vaccine, general; vasotropic; vulnerary.
XX
OS Homo sapiens.
XX
CC PN WO2020260722-A1.
XX
CC PD 30-DEC-2020.
XX
CC PF 29-JUN-2020; 2020WO-EP068314.
XX
PR 28-JUN-2019; 2019GB-00009393.
XX
CC PA (GENT-) GEN2 NEUROSCI LTD.
XX
CC PI Livesey FJ, Jones C;
XX
DR WPI; 2021-01297P/011.
XX
CC PT New isolated synthetic or recombinant peptide comprising epitope, useful
CC PT for preventing or treating tauopathy e.g. Alzheimer's disease,
CC PT amyotrophic lateral sclerosis/parkinsonism-dementia complex, argyrophilic
CC PT grains disease.
XX
CC PS Claim 1; SEQ ID NO 1; 98pp; English.
XX
CC The present invention relates to a novel isolated synthetic or
CC recombinant peptide for generating a binding molecule which is used for
CC preventing or treating tauopathy in a subject. The epitope comprises an
CC amino acid sequence of SEQ ID NO: 1 (see BIU57633) which corresponds to
CC residues 369-381 of human tau protein of SEQ ID NO: 2 (see BIU57634). The
CC invention further relates to: (1) a binding molecule capable of binding
CC specifically to the isolated synthetic or recombinant peptide; (2) an
CC antigen-binding protein or antibody or its antigen-binding fragment
CC capable of binding specifically to the isolated synthetic or recombinant
CC peptide; (3) an isolated recombinant DNA or RNA sequence comprising a
CC sequence encoding the isolated recombinant peptide, binding molecule and
CC antigen-binding protein; (4) a host cell comprising the DNA or RNA
CC sequence; (5) a method for making an isolated recombinant peptide,
CC binding molecule or antigen binding protein such as an antibody or its
CC fragment; (6) a composition comprising the isolated recombinant peptide,
CC binding molecule or antigen binding protein; (7) an immunogenic
CC composition or vaccine capable of inducing an immunological response in a
CC subject inoculated with the composition; (8) the use of the isolated
CC recombinant peptide, binding molecule, antigen-binding protein or
CC composition for identifying human tau protein; and (9) a diagnostic kit
CC comprising an isolated recombinant peptide, binding molecule, antigen-
CC binding protein or composition and a reagent capable of detecting an
CC immunological complex which comprises the isolated recombinant peptide
CC binding molecule. The isolated recombinant peptide is used for generating
CC the binding molecule for preventing or treating tauopathy alzheimer's
CC disease, amyotrophic lateral sclerosis/parkinsonism-dementia complex,
CC argyrophilic grains disease, beta-propeller protein associated
CC neurodegeneration (BPAN), British type amyloid angiopathy, cerebral
CC amyloid angiopathy, creutzfeldt-jakob disease, dementia pugilistica,
CC diffuse neurofibrillary tangles with calcification, down's syndrome,
CC chronic traumatic encephalopathy (CTE), corticobasal degeneration (CBD),
CC gerstmann-straussler-scheinker disease, hallervorden-spatz disease, body
CC myositis, multiple system atrophy, myotonic dystrophy, niemann-pick
CC disease type C, pick's disease, post encephalitic parkinsonism, primary
CC age-related tauopathy (PART), prion protein cerebral amyloid angiopathy,
CC progressive subcortical gliosis, progressive supranuclear palsy (PSP),
CC globular glial tauopathy, parkinsonism dementia complex of guam,
CC progressive non-fluent aphasia, multi-infarct dementia, ischemic stroke,
CC traumatic brain injury (TBI) and stroke in the subject.
XX
SQ Sequence 13 AA;
Query Match 100.0%; Score 13; Length 13;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KKEITHKLTFREN 13
|||||||||||||
Db 1 KKEITHKLTFREN 13
SEQ ID NO:150
BIU57633
(NOTE: this sequence has 1 duplicate in the database searched)
ID BIU57633 standard; peptide; 13 AA.
XX
AC BIU57633;
XX
DT 18-FEB-2021 (first entry)
XX
DE Human tau protein epitope (369-381), SEQ 1.
XX
KW 2N4R tau; Tau protein; alzheimers disease; antibody production;
KW antibody therapy; antimicrobial-gen.; antiparkinsonian; aphasia;
KW brain disease; cerebral amyloid angiopathy; cerebroprotective;
KW creutzfeldt jakob disease; diagnostic test; down syndrome; epitope;
KW frontotemporal dementia; genetic-disease-gen.;
KW gerstmann straussler scheinker disease; growth-disorder-gen.;
KW hallervorden-spatz syndrome; immune stimulation; immuno-diagnosis;
KW ischemic stroke; metabolic-gen.; motor neurone disease;
KW multi-infarct dementia; multiple system atrophy; muscular-gen.; myositis;
KW myotonic dystrophy; neuroprotective; niemann pick disease type c;
KW nootropic; parkinsons disease dementia; prophylactic to disease;
KW protein detection; stroke; therapeutic; traumatic brain injury;
KW vaccine, general; vasotropic; vulnerary.
XX
OS Homo sapiens.
XX
CC PN WO2020260722-A1.
XX
CC PD 30-DEC-2020.
XX
CC PF 29-JUN-2020; 2020WO-EP068314.
XX
PR 28-JUN-2019; 2019GB-00009393.
XX
CC PA (GENT-) GEN2 NEUROSCI LTD.
XX
CC PI Livesey FJ, Jones C;
XX
DR WPI; 2021-01297P/011.
XX
CC PT New isolated synthetic or recombinant peptide comprising epitope, useful
CC PT for preventing or treating tauopathy e.g. Alzheimer's disease,
CC PT amyotrophic lateral sclerosis/parkinsonism-dementia complex, argyrophilic
CC PT grains disease.
XX
CC PS Claim 1; SEQ ID NO 1; 98pp; English.
XX
CC The present invention relates to a novel isolated synthetic or
CC recombinant peptide for generating a binding molecule which is used for
CC preventing or treating tauopathy in a subject. The epitope comprises an
CC amino acid sequence of SEQ ID NO: 1 (see BIU57633) which corresponds to
CC residues 369-381 of human tau protein of SEQ ID NO: 2 (see BIU57634). The
CC invention further relates to: (1) a binding molecule capable of binding
CC specifically to the isolated synthetic or recombinant peptide; (2) an
CC antigen-binding protein or antibody or its antigen-binding fragment
CC capable of binding specifically to the isolated synthetic or recombinant
CC peptide; (3) an isolated recombinant DNA or RNA sequence comprising a
CC sequence encoding the isolated recombinant peptide, binding molecule and
CC antigen-binding protein; (4) a host cell comprising the DNA or RNA
CC sequence; (5) a method for making an isolated recombinant peptide,
CC binding molecule or antigen binding protein such as an antibody or its
CC fragment; (6) a composition comprising the isolated recombinant peptide,
CC binding molecule or antigen binding protein; (7) an immunogenic
CC composition or vaccine capable of inducing an immunological response in a
CC subject inoculated with the composition; (8) the use of the isolated
CC recombinant peptide, binding molecule, antigen-binding protein or
CC composition for identifying human tau protein; and (9) a diagnostic kit
CC comprising an isolated recombinant peptide, binding molecule, antigen-
CC binding protein or composition and a reagent capable of detecting an
CC immunological complex which comprises the isolated recombinant peptide
CC binding molecule. The isolated recombinant peptide is used for generating
CC the binding molecule for preventing or treating tauopathy alzheimer's
CC disease, amyotrophic lateral sclerosis/parkinsonism-dementia complex,
CC argyrophilic grains disease, beta-propeller protein associated
CC neurodegeneration (BPAN), British type amyloid angiopathy, cerebral
CC amyloid angiopathy, creutzfeldt-jakob disease, dementia pugilistica,
CC diffuse neurofibrillary tangles with calcification, down's syndrome,
CC chronic traumatic encephalopathy (CTE), corticobasal degeneration (CBD),
CC gerstmann-straussler-scheinker disease, hallervorden-spatz disease, body
CC myositis, multiple system atrophy, myotonic dystrophy, niemann-pick
CC disease type C, pick's disease, post encephalitic parkinsonism, primary
CC age-related tauopathy (PART), prion protein cerebral amyloid angiopathy,
CC progressive subcortical gliosis, progressive supranuclear palsy (PSP),
CC globular glial tauopathy, parkinsonism dementia complex of guam,
CC progressive non-fluent aphasia, multi-infarct dementia, ischemic stroke,
CC traumatic brain injury (TBI) and stroke in the subject.
XX
SQ Sequence 13 AA;
Query Match 100.0%; Score 7; Length 13;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 THKLTFR 7
|||||||
Db 5 THKLTFR 11
SEQ ID NO:20-SEQ ID NO:21-SEQ ID NO:164
BIU57750
(NOTE: this sequence has 2 duplicates in the database searched)
ID BIU57750 standard; protein; 135 AA.
XX
AC BIU57750;
XX
DT 18-FEB-2021 (first entry)
XX
DE Anti-2N4R tau antibody (Clone 2) heavy chain variable region, SEQ 118.
XX
KW 2N4R tau; Tau protein; alzheimers disease; antibody production;
KW antibody therapy; antimicrobial-gen.; antiparkinsonian; aphasia;
KW brain disease; cerebral amyloid angiopathy; cerebroprotective;
KW creutzfeldt jakob disease; diagnostic test; down syndrome;
KW frontotemporal dementia; genetic-disease-gen.;
KW gerstmann straussler scheinker disease; growth-disorder-gen.;
KW hallervorden-spatz syndrome; heavy chain variable region;
KW immune stimulation; immuno-diagnosis; ischemic stroke; metabolic-gen.;
KW monoclonal antibody; motor neurone disease; multi-infarct dementia;
KW multiple system atrophy; muscular-gen.; myositis; myotonic dystrophy;
KW neuroprotective; niemann pick disease type c; nootropic;
KW parkinsons disease dementia; prophylactic to disease; protein detection;
KW stroke; therapeutic; traumatic brain injury; vaccine, general;
KW vasotropic; vulnerary.
XX
OS Oryctolagus cuniculus.
XX
CC PN WO2020260722-A1.
XX
CC PD 30-DEC-2020.
XX
CC PF 29-JUN-2020; 2020WO-EP068314.
XX
PR 28-JUN-2019; 2019GB-00009393.
XX
CC PA (GENT-) GEN2 NEUROSCI LTD.
XX
CC PI Livesey FJ, Jones C;
XX
DR WPI; 2021-01297P/011.
XX
CC PT New isolated synthetic or recombinant peptide comprising epitope, useful
CC PT for preventing or treating tauopathy e.g. Alzheimer's disease,
CC PT amyotrophic lateral sclerosis/parkinsonism-dementia complex, argyrophilic
CC PT grains disease.
XX
CC PS Claim 9; SEQ ID NO 118; 98pp; English.
XX
CC The present invention relates to a novel isolated synthetic or
CC recombinant peptide for generating a binding molecule which is used for
CC preventing or treating tauopathy in a subject. The epitope comprises an
CC amino acid sequence of SEQ ID NO: 1 (see BIU57633) which corresponds to
CC residues 369-381 of human tau protein of SEQ ID NO: 2 (see BIU57634). The
CC invention further relates to: (1) a binding molecule capable of binding
CC specifically to the isolated synthetic or recombinant peptide; (2) an
CC antigen-binding protein or antibody or its antigen-binding fragment
CC capable of binding specifically to the isolated synthetic or recombinant
CC peptide; (3) an isolated recombinant DNA or RNA sequence comprising a
CC sequence encoding the isolated recombinant peptide, binding molecule and
CC antigen-binding protein; (4) a host cell comprising the DNA or RNA
CC sequence; (5) a method for making an isolated recombinant peptide,
CC binding molecule or antigen binding protein such as an antibody or its
CC fragment; (6) a composition comprising the isolated recombinant peptide,
CC binding molecule or antigen binding protein; (7) an immunogenic
CC composition or vaccine capable of inducing an immunological response in a
CC subject inoculated with the composition; (8) the use of the isolated
CC recombinant peptide, binding molecule, antigen-binding protein or
CC composition for identifying human tau protein; and (9) a diagnostic kit
CC comprising an isolated recombinant peptide, binding molecule, antigen-
CC binding protein or composition and a reagent capable of detecting an
CC immunological complex which comprises the isolated recombinant peptide
CC binding molecule. The isolated recombinant peptide is used for generating
CC the binding molecule for preventing or treating tauopathy alzheimer's
CC disease, amyotrophic lateral sclerosis/parkinsonism-dementia complex,
CC argyrophilic grains disease, beta-propeller protein associated
CC neurodegeneration (BPAN), British type amyloid angiopathy, cerebral
CC amyloid angiopathy, creutzfeldt-jakob disease, dementia pugilistica,
CC diffuse neurofibrillary tangles with calcification, down's syndrome,
CC chronic traumatic encephalopathy (CTE), corticobasal degeneration (CBD),
CC gerstmann-straussler-scheinker disease, hallervorden-spatz disease, body
CC myositis, multiple system atrophy, myotonic dystrophy, niemann-pick
CC disease type C, pick's disease, post encephalitic parkinsonism, primary
CC age-related tauopathy (PART), prion protein cerebral amyloid angiopathy,
CC progressive subcortical gliosis, progressive supranuclear palsy (PSP),
CC globular glial tauopathy, parkinsonism dementia complex of guam,
CC progressive non-fluent aphasia, multi-infarct dementia, ischemic stroke,
CC traumatic brain injury (TBI) and stroke in the subject.
XX
SQ Sequence 135 AA;
Query Match 75.1%; Score 118.6; Length 135;
Best Local Similarity 34.7%;
Matches 25; Conservative 2; Mismatches 1; Indels 44; Gaps 2;
Qy 1 SYAMA--------------CIDRRGGTFYASWVKG------------------------- 21
||||| ||||||||||||||||
Db 36 SYAMAWVRQAPGKGLEWIGCIDRRGGTFYASWVKGRFTISKTSTTVDLKMTSLTTEDTAT 95
Qy 22 -----DAGSFHP 28
|:|:| |
Db 96 YFCARDSGAFDP 107
SEQ ID NO:186
BIU57750
(NOTE: this sequence has 2 duplicates in the database searched)
ID BIU57750 standard; protein; 135 AA.
XX
AC BIU57750;
XX
DT 18-FEB-2021 (first entry)
XX
DE Anti-2N4R tau antibody (Clone 2) heavy chain variable region, SEQ 118.
XX
KW 2N4R tau; Tau protein; alzheimers disease; antibody production;
KW antibody therapy; antimicrobial-gen.; antiparkinsonian; aphasia;
KW brain disease; cerebral amyloid angiopathy; cerebroprotective;
KW creutzfeldt jakob disease; diagnostic test; down syndrome;
KW frontotemporal dementia; genetic-disease-gen.;
KW gerstmann straussler scheinker disease; growth-disorder-gen.;
KW hallervorden-spatz syndrome; heavy chain variable region;
KW immune stimulation; immuno-diagnosis; ischemic stroke; metabolic-gen.;
KW monoclonal antibody; motor neurone disease; multi-infarct dementia;
KW multiple system atrophy; muscular-gen.; myositis; myotonic dystrophy;
KW neuroprotective; niemann pick disease type c; nootropic;
KW parkinsons disease dementia; prophylactic to disease; protein detection;
KW stroke; therapeutic; traumatic brain injury; vaccine, general;
KW vasotropic; vulnerary.
XX
OS Oryctolagus cuniculus.
XX
CC PN WO2020260722-A1.
XX
CC PD 30-DEC-2020.
XX
CC PF 29-JUN-2020; 2020WO-EP068314.
XX
PR 28-JUN-2019; 2019GB-00009393.
XX
CC PA (GENT-) GEN2 NEUROSCI LTD.
XX
CC PI Livesey FJ, Jones C;
XX
DR WPI; 2021-01297P/011.
XX
CC PT New isolated synthetic or recombinant peptide comprising epitope, useful
CC PT for preventing or treating tauopathy e.g. Alzheimer's disease,
CC PT amyotrophic lateral sclerosis/parkinsonism-dementia complex, argyrophilic
CC PT grains disease.
XX
CC PS Claim 9; SEQ ID NO 118; 98pp; English.
XX
CC The present invention relates to a novel isolated synthetic or
CC recombinant peptide for generating a binding molecule which is used for
CC preventing or treating tauopathy in a subject. The epitope comprises an
CC amino acid sequence of SEQ ID NO: 1 (see BIU57633) which corresponds to
CC residues 369-381 of human tau protein of SEQ ID NO: 2 (see BIU57634). The
CC invention further relates to: (1) a binding molecule capable of binding
CC specifically to the isolated synthetic or recombinant peptide; (2) an
CC antigen-binding protein or antibody or its antigen-binding fragment
CC capable of binding specifically to the isolated synthetic or recombinant
CC peptide; (3) an isolated recombinant DNA or RNA sequence comprising a
CC sequence encoding the isolated recombinant peptide, binding molecule and
CC antigen-binding protein; (4) a host cell comprising the DNA or RNA
CC sequence; (5) a method for making an isolated recombinant peptide,
CC binding molecule or antigen binding protein such as an antibody or its
CC fragment; (6) a composition comprising the isolated recombinant peptide,
CC binding molecule or antigen binding protein; (7) an immunogenic
CC composition or vaccine capable of inducing an immunological response in a
CC subject inoculated with the composition; (8) the use of the isolated
CC recombinant peptide, binding molecule, antigen-binding protein or
CC composition for identifying human tau protein; and (9) a diagnostic kit
CC comprising an isolated recombinant peptide, binding molecule, antigen-
CC binding protein or composition and a reagent capable of detecting an
CC immunological complex which comprises the isolated recombinant peptide
CC binding molecule. The isolated recombinant peptide is used for generating
CC the binding molecule for preventing or treating tauopathy alzheimer's
CC disease, amyotrophic lateral sclerosis/parkinsonism-dementia complex,
CC argyrophilic grains disease, beta-propeller protein associated
CC neurodegeneration (BPAN), British type amyloid angiopathy, cerebral
CC amyloid angiopathy, creutzfeldt-jakob disease, dementia pugilistica,
CC diffuse neurofibrillary tangles with calcification, down's syndrome,
CC chronic traumatic encephalopathy (CTE), corticobasal degeneration (CBD),
CC gerstmann-straussler-scheinker disease, hallervorden-spatz disease, body
CC myositis, multiple system atrophy, myotonic dystrophy, niemann-pick
CC disease type C, pick's disease, post encephalitic parkinsonism, primary
CC age-related tauopathy (PART), prion protein cerebral amyloid angiopathy,
CC progressive subcortical gliosis, progressive supranuclear palsy (PSP),
CC globular glial tauopathy, parkinsonism dementia complex of guam,
CC progressive non-fluent aphasia, multi-infarct dementia, ischemic stroke,
CC traumatic brain injury (TBI) and stroke in the subject.
XX
SQ Sequence 135 AA;
Query Match 80.1%; Score 487; Length 135;
Best Local Similarity 83.0%;
Matches 93; Conservative 7; Mismatches 10; Indels 2; Gaps 1;
Qy 4 LQESGPGLVKPSETLSLTCTVSGIDLSSYAMAWVRQAPGKGLEWIGCIDRRGGTFYASWV 63
::||| || | |:||||||||||||||||||||||||||||||||||||||||||||
Db 9 VEESGGRLVTPGTPLTLTCTVSGIDLSSYAMAWVRQAPGKGLEWIGCIDRRGGTFYASWV 68
Qy 64 KGRFTISKDTSKTTVDLQMTSLTAEDTATYFCARDAGSFHPWGQGTLVTVSS 115
|||||||| : |||||:||||| |||||||||||:|:| ||| ||||||||
Db 69 KGRFTISK--TSTTVDLKMTSLTTEDTATYFCARDSGAFDPWGPGTLVTVSS 118
WO2021005019 teaches an antibody against human tau epitope aa 369-381 (SEQ ID NO:122), which is 100% identical to aa 369-381 (instant SEQ ID NO:1) of human 2N4R tau (instant SEQ ID NO:2) (see the sequence alignment).
SEQ ID NO:1
BIW91527
ID BIW91527 standard; peptide; 13 AA.
XX
AC BIW91527;
XX
DT 04-MAR-2021 (first entry)
XX
DE Human 2N4R tau1-441 protein derived epitope (369-381) SEQ ID 122.
XX
KW 2N4R; Tau protein; antibody production; antibody therapy;
KW diagnostic test; elisa; epitope; immune stimulation; immuno-diagnosis;
KW immunoassay; neurodegenerative disease; neuroprotective;
KW prophylactic to disease; protein detection; protein production;
KW protein therapy; recombinant protein; therapeutic; vaccine, general.
XX
OS Homo sapiens.
XX
CC PN WO2021005019-A1.
XX
CC PD 14-JAN-2021.
XX
CC PF 06-JUL-2020; 2020WO-EP069039.
XX
PR 05-JUL-2019; 2019GB-00009721.
XX
CC PA (GENT-) GEN2 NEUROSCIENCE LTD.
XX
CC PI Livesey F, Jones C;
XX
DR WPI; 2021-064567/012.
XX
CC PT Isolated synthetic or recombinant peptide for use as a peptide vaccine,
CC PT comprises epitope, peptide consisting of residues of human 2N4R and an N-
CC PT terminal cysteine residue or C-terminal cysteine residue, where peptide
CC PT is not phosphorylated.
XX
CC PS Example 19; SEQ ID NO 122; 129pp; English.
XX
CC The present invention relates to an isolated synthetic or recombinant
CC peptide useful for investigating, diagnosing and treating tauopathies.
CC The peptide comprises an epitope consisting of residues 396-410 of human
CC 2N4R shown in SEQ ID NO: 2 (see BIW91407) and an N-terminal or C-terminal
CC cysteine residue, where the peptide is not phosphorylated. The invention
CC further relates to: (1) a binding molecule capable of binding
CC specifically to the isolated peptide or an epitope; (2) an antigen-
CC binding protein such as an antibody or its antigen-binding fragment
CC comprising an antigen-binding site comprising complementarity determining
CC regions (CDRs) of heavy chain HCDR1, HCRD2, HCDR3, and light chain LCDR1,
CC LCDR2, and LCDR3; (3) an isolated recombinant DNA or RNA sequence
CC encoding the isolated peptide, binding molecule, antigen-binding protein
CC or its fragment; (4) a method for making the isolated peptide, binding
CC molecule, antigen-binding protein or its fragment; (5) a composition
CC comprising the isolated peptide, binding molecule, antigen-binding
CC protein or its fragment and a diluent; (6) an immunogenic composition
CC capable of inducing an immunological response in a subject; and (7) a
CC diagnostic kit which comprises the isolated peptide, binding molecule,
CC antigen-binding protein or its fragment or a composition and a reagent
CC capable of detecting an immunological complex by ELISA or an alternative
CC immunoassay. The isolated synthetic or recombinant peptide is useful as a
CC peptide vaccine, and for diagnosing, preventing and treating tauopathy
CC selected from Alzheimers disease, amyotrophic lateral
CC sclerosis/parkinsonism-dementia complex, argyrophilic grains disease,
CC beta-propeller protein associated neurodegeneration, British type amyloid
CC angiopathy, cerebral amyloid angiopathy, Creutzfeldt-Jakob disease,
CC dementia pugilistica, diffuse neurofibrillary tangles with calcification,
CC Down's syndrome, chronic traumatic encephalopathy, corticobasal
CC degeneration, frontotemporal dementia, frontotemporal dementia and
CC parkinsonism linked to chromosome 17, frontotemporal lobar degeneration,
CC Gerstmann-Straussler-Scheinker disease, Hallervorden-Spatz disease,
CC inclusion body myositis, multiple system atrophy, myotonic dystrophy,
CC Niemann-pick disease type C, non-guamanian motor neuron disease with
CC neurofibrillary tangles, Picks disease, post-encephalitic parkinsonism,
CC primary age-related tauopathy, prion protein cerebral amyloid angiopathy,
CC progressive subcortical gliosis, progressive supranuclear palsy, subacute
CC sclerosing panencephalitis, tangle-dominant dementia, globular glial
CC tauopathy, parkinsonism dementia complex of Guam, progressive non-fluent
CC aphasia, multi-infarct dementia, ischemic stroke, traumatic brain injury
CC and stroke.
XX
SQ Sequence 13 AA;
Query Match 100.0%; Score 68; Length 13;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KKIETHKLTFREN 13
|||||||||||||
Db 1 KKIETHKLTFREN 13
19. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
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 at 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
March 7, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675