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
2. The election without traverse filed 01/09/2026 in response to the Office Action of 12/23/2025 is acknowledged and has been entered.
Applicant has elected Group I, claims 1-9 and 13, drawn to an isolated monoclonal antibody or antigen-binding fragment thereof that binds to a tau protein at an epitope of the tau protein consisting of or within the amino acid sequence of SEQ ID NO: 1, wherein the antibody or antigen-binding fragment thereof binds paired helical filament (PHF)-tau, human PHF-tau.
Additionally, Applicant has elected the antibodies of claim 3b (relating to SEQ ID NOs: 14, 15, 16, 17, 18, and 19) and claim 6b (relating to SEQ ID NOs: 12 and 13) as species of antibodies.
3. Claims 1-20 are pending in the application. Claims 8, 10-12 and 14-20 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim.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 01/09/2026.
Claims 1-7, 9 and 13 are currently under prosecution.
Priority
5. Applicant’s claim under 35 U.S.C. §§ 119(e) and/or 365(c) for benefit of the earlier filing date of applications, is acknowledged.
Claim Objections
6. Claim 13 is objected to because of the following informalities:
Claim 13 the phrase “any one of claim 1” should be "claim 1”.
Appropriate correction is required.
Improper Markush Grouping Rejection
7. Claims 3-7 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 antibodies recited in claims 3-7 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: because the antibodies do not share a “single structural similarity”.
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
8. 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.
9. 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.
10. Claims 1-2 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.
Claim 1 recites the phrase "preferably", the phrase "preferably" 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.
Claim 2(b) recites “the epitope of the tau protein comprises one or more of phosphorylated T427, phosphorylated S433 and phosphorylated S435 of the tau protein, but does not comprise all of phosphorylated T427, phosphorylated S433 and phosphorylated S435”; one or more of phosphorylated T427, phosphorylated S433 and phosphorylated S435 of the tau protein include all of phosphorylated T427, phosphorylated S433 and phosphorylated S435. Thus, the recitation of claim 2(b) is self-contradictory.
11. The following is a quotation 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.
12. The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
13. Claims 1-2, 4-5 and 13 remain/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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
1) MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species. Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
On 22 February 2018, the USPTO provided a Memorandum clarifying the Written Description Guidelines for claims drawn to antibodies, which can be found at www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf. That Memorandum indicates that, in compliance with recent legal decisions, the disclosure of a full characterized antigen no longer is sufficient written description of an antibody to that antigen. Accordingly, the instant claims have been re-evaluated in view of that guidance.
Scope of the claimed genus
Claims 1-2 and 13 are drawn to an isolated monoclonal antibody or antigen-binding fragment thereof that binds to a tau protein at an epitope of the tau protein set forth in the amino acid sequence of SEQ ID NO: 1.
State of the Relevant Art
SEQ ID NO: 1 is a fragment of a tau protein, it is known in the art; see below sequence alignment 1.
As was well-known in the antibody art, antibodies as a class share an overall structure generally comprising two heavy chain polypeptides that each comprises a heavy chain variable region (VH) and a heavy chain constant region made up of several domain (CH1, hinge, CH2, CH3, and for some antibodies, a CH4). Each of the heavy chains pairs with a light chain polypeptide that comprises a light chain variable region (VL) and a constant region. But while this overall structure is shared amongst antibodies from a wide variety of sources (human, rat, mouse, rabbit), the structure each antibody uses to bind its particular epitope on an antigen is structurally distinct and is formed by a recombination event that results in high variability at the amino acid sequence level. By the time the invention was made, it is well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three “complementarity determining regions” (“CDRs”) which provide the majority of the contact residues for the binding of the antibody to its target epitope. E.g., Almagro & Fransson, Frontiers in Bioscience 2008; 13:1619-33 (see Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1). Chimeric antibodies comprise the heavy and light chain variable regions of a rodent antibody linked to human constant regions and preserve the entirety of the VH and VL of the parent antibody. Id. at 1619-20. Humanized antibodies comprise only the CDRs, or in some cases an abbreviated subset of residues within the CDRs, of a parental rodent antibody in the context of human framework sequences. Id. at Section 4. All of the CDRs of the heavy and light chain, in their proper order of CDR1, then 2, then 3, and in the context of framework sequences which maintain their required conformation are generally required to produce a humanized antibody in which the heavy and light chains associate to form an antigen-binding region that binds the same antigen as the parental rodent antibody. Id. at Section 4. Almagro provides a detailed discussion regarding various methods of humanization, including rationale design approaches and empirical approaches based on random screening. Almagro, Sections 4 and 5.
Examples of antigen binding domains comprising only a VH (or less commonly, a VL) that in turn comprise only three CDRs certainly do exist in the literature, but those antibodies generally comprise unique structures such as CDR1 and CDR3’s that are elongated in length and that are often disulfide linked. E.g., De Genst et al., Dev Comp Immunol 2006; 30:187-98. “Shuffling” of the VL (or less commonly the VH) had also been used to improve affinity of a parent antibody in certain instances. But the procedure generally required a "dominant" VH (i.e., a VH that is primarily responsible for antigen specificity). E.g., Yoshinaga et al., J. Biochem 2008; 143: 593-601.
Overall, at the time the invention was made, the level of skill for preparing antibodies and then selecting those antibodies with desired functional properties was high. However, even if a selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010); see also Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1876 (Fed. Cir. 2011) (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”) Absent the conserved structure provided by all six CDRs of a parental antibody in the context of appropriate VH and VL framework sequences, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what an antibody with a particular set of functional properties would look like structurally.
Summary of Species disclosed in the original specification
Although the specification teaches SEQ ID NO: 1 (see page 54 of the instant specification); however, the specification does not provide a representative number of species to which the claimed a genus of antibodies that specifically binds to the SEQ ID NO: 1.
Are the disclosed species representative of the claimed genus?
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
However, the specification does not provide a representative number of species to which the claimed a genus of antibodies that specifically binds to the SEQ ID NO: 1.
Identifying characteristics and structure/function correlation
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics; i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. To meet this requirement in the instant case, the specification must describe structural features that convey the claimed binding activity, a prerequisite for utility in the recited composition.
As noted above, the art generally accepted that the combination of the CDRs within the VH and VL pair of an antibody were essential for binding specificity. But the specification does not describe what residues within the CDRs confer the binding activity claimed. Accordingly, the skilled artisan would not be able to discern a structure/function correlation for antibodies other than those comprising either all six CDRs (in the context of VH and VL regions) of one parental antibody, or the VH and VL of one parental antibody.
Further, the specification does not show that either the VH or the VL is “dominant” and could be paired with other VH or VL to form a new antibody that still bound the same antigen. It is again acknowledged that the skilled artisan possessed the methodology needed to “shuffle” the VL and/or VH and screen for binders. But that methodology did not allow the skilled artisan to visualize the structure of the alternate VH/VL chains prior to the step of screening. Accordingly, absent supporting evidence of a “dominant” VH or VL, the recitation of only a VH or only a VL does not provide a structure that the skilled artisan would consider to correlate with binding function.
For all of the reasons presented above, one of skill in the art would not know which of the countless other antibodies that meet the highly general structural requirements of the claims would also be able to specifically bind the SEQ ID NO: 1. And none of the dependent claims provide sufficient additional structure or a structure/function correlation to provide an adequate written description of the genera claimed. Therefore, the skilled artisan would not reasonably conclude that the inventors, at the time the application was filed, had full possession of antibodies as broadly claimed. Given the lack of shared structural properties that provide the claimed binding activity, the limited number of species described, and the fact that the species that were described cannot be considered representative of the broad genus, Applicant was not in possession of the invention as claimed.
2) Turning to a new issue, the claims 4-5 are drawn to the isolated monoclonal antibody or antigen-binding fragment thereof of claim 1, comprising a heavy chain variable region having a polypeptide sequence at least 90% identical to SEQ ID NO: 2, 12, 22, 30 or 38, or a light chain variable region having a polypeptide sequence at least 90% identical to SEQ ID NO: 3, 13, 23, 31 or 39.
Thus, the claim is drawn to a genus of antibodies comprise an amino acid sequence that has at least 90% identical to SEQ ID NOs: 2-3, 12-13, 22-23, 30-31, and 38-39. Additionally, the claims 4-5 are directed to a genus of antibodies comprising a miss-matched light chain and heavy chain.
Although the specification teaches SEQ ID NOs: 2-3, 12-13, 22-23, 30-31, and 38-39 (see pages 21-23 of the published application); however, the specification does not teach that an antibody comprises an amino acid sequence that has at least 90% identical to SEQ ID NOs: 2-3, 12-13, 22-23, 30-31 and 38-39, or miss-matched light chain and heavy chain would have or retain the activity or function of SEQ ID NOs: 2-3, 12-13, 22-23, 30-31, and 38-39.
Given the fact that the claims are drawn to a genus of antibodies comprise an amino acid sequence that has at least 90% identical to SEQ ID NOs: 2-3, 12-13, 22-23, 30-31 and 38-39, and miss-matched light chain and heavy chain, which have no particular function or activity, there is no correlation between any one particularly identifying structural feature and any one particularly identifying functional feature. Consequently, it is submitted that the skilled artisan could not immediately envision, recognize or distinguish at least a substantial number of the genus of antibodies comprise an amino acid sequence that has at least 90% identical to SEQ ID NOs: 2-3, 12-13, 22-23, 30-31 and 38-39 to which the claim is directed.
Although the specification teaches SEQ ID NOs: 2-3, 12-13, 22-23, 30-31 and 38-39, the SEQ ID NOs are not reasonably representative of the genus of antibodies comprise an amino acid sequence that has at least 90% identical to SEQ ID NOs: 2-3, 12-13, 22-23, 30-31 and 38-39. This is largely because each amino acid sequence that has at least 90% identical to SEQ ID NOs: 2-3, 12-13, 22-23, 30-31 and 38-39 has substantially varying structure and need not have any particular function or activity.
Guidelines states, “[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was ‘ready for patenting’ such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention” (Id. at 1104). “Guidelines” further states, “[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus” (Id. at 1106); accordingly, it follows that an adequate written description of a genus cannot be achieved in the absence of a disclosure of at least one species within the genus. Moreover, because the claims encompass a genus of antibodies comprise an amino acid sequence that has at least 90% identical to SEQ ID NOs: 2-3, 12-13, 22-23, 30-31 and 38-39, and miss-matched light chain and heavy chain, which vary both structurally and functionally, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. In this instance, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; Applicant has not shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; and Applicant has not described distinguishing identifying characteristics sufficient to show that Applicant was in possession of the claimed invention at the time the application was filed.
Thus, it is submitted that the instant claims, and the disclosure describing the claimed subject matter, fails to satisfy the written description requirement set forth under 35 U.S.C. § 112, first paragraph.
14. 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
15. 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.
16. Claims 1-2 and 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zanelli et al. (WO 2018006092, published on 01/04/2018).
Claims 1-7, 9 and 13 are herein drawn to an isolated monoclonal antibody or antigen-binding fragment thereof that binds to a tau protein at an epitope of the tau protein consisting of or within the amino acid sequence of SEQ ID NO: 1, wherein the antibody or antigen-binding fragment thereof binds paired helical filament (PHF)-tau, human PHF-tau; wherein the epitope of the tau protein comprises either one of phosphorylated S433 or phosphorylated S435 of the tau protein, but does not comprise phosphorylated S433 and phosphorylated S435.
Zanelli et al. teach a method of generating anti-tau antibodies that binds to SEQ ID NO: 6, 8, or 10; see entire document, e.g., page 16-lines 1-7, pages 70 and 147, claims 66 and 99.
SEQ ID NO: 6, 8 and 10 of Zanelli et al. are 100% identical with the instant claimed SEQ ID NO: 1; see below sequence alignment 2.
Zanelli et al. teach phosphorylation site of Tau protein includes T427, S433, or S435; see page 70-lines 12-13.
Zanelli et al. teach a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers and/or excipients; see page 104.
Double Patenting
17. 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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
18. Claims 1-7, 9 and 13 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-6 of copending Application No. 18/284209. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons:
Claims 1-7, 9 and 13 are herein drawn to an isolated monoclonal antibody or antigen-binding fragment thereof that binds to a tau protein at an epitope of the tau protein consisting of or within the amino acid sequence of SEQ ID NO: 1, wherein the antibody or antigen-binding fragment thereof binds paired helical filament (PHF)-tau, human PHF-tau.
Claims 1-6 of copending Application No. 18/284209 are drawn to an isolated humanized antibody or antigen-binding fragment thereof that binds to a tau protein at an epitope of the tau protein consisting of or within the amino acid sequence of SEQ ID NO: 1, wherein the antibody or antigen-binding fragment thereof binds paired helical filament (PHF)-tau, preferably human PHF-tau, wherein the epitope of the tau protein comprises one or more of phosphorylated T427, phosphorylated S433 and phosphorylated S435 of the tau protein, but does not comprise all of phosphorylated T427, phosphorylated S433 and phosphorylated S435.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Conclusion
19. No claim is allowed.
20. Any inquiry concerning this communication or earlier communications from the examiner should be directed to YAN XIAO whose telephone number is (571)270-3578. The examiner can normally be reached M-F 8-5 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, Samira Jean-Louis can be reached on 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YAN XIAO/Primary Examiner, Art Unit 1642
Sequence alignment 1
A0AAW0I1Q7_MYOGA
ID A0AAW0I1Q7_MYOGA Unreviewed; 110 AA.
AC A0AAW0I1Q7;
DT 27-NOV-2024, integrated into UniProtKB/TrEMBL.
DT 27-NOV-2024, sequence version 1.
DT 08-OCT-2025, entry version 5.
DE RecName: Full=Microtubule-associated protein {ECO:0000256|RuleBase:RU000686};
GN ORFNames=U0070_019702 {ECO:0000313|EMBL:KAK7808445.1};
OS Myodes glareolus (Bank vole) (Clethrionomys glareolus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Arvicolinae; Myodes.
OX NCBI_TaxID=447135 {ECO:0000313|EMBL:KAK7808445.1, ECO:0000313|Proteomes:UP001488838};
RN [1] {ECO:0000313|EMBL:KAK7808445.1, ECO:0000313|Proteomes:UP001488838}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=V071 {ECO:0000313|EMBL:KAK7808445.1};
RX PubMed=38187646;
RA Calamari Z.T., Song A., Cohen E., Akter M., Roy R.D., Hallikas O.,
RA Christensen M.M., Li P., Marangoni P., Jernvall J., Klein O.D.;
RT "Conserved and derived expression patterns and positive selection on dental
RT genes reveal complex evolutionary context of ever-growing rodent molars.";
RL bioRxiv 0:0-0(2023).
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000256|ARBA:ARBA00004245, ECO:0000256|RuleBase:RU000686}.
CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ
CC whole genome shotgun (WGS) entry which is preliminary data.
CC {ECO:0000313|EMBL:KAK7808445.1}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; JBBHLL010000239; KAK7808445.1; -; Genomic_DNA.
DR Proteomes; UP001488838; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0043005; C:neuron projection; IEA:TreeGrafter.
DR GO; GO:0008017; F:microtubule binding; IEA:InterPro.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IEA:TreeGrafter.
DR GO; GO:0031175; P:neuron projection development; IEA:TreeGrafter.
DR InterPro; IPR027324; MAP2/MAP4/Tau.
DR InterPro; IPR001084; MAP_tubulin-bd_rpt.
DR PANTHER; PTHR11501; MICROTUBULE-ASSOCIATED PROTEIN; 1.
DR PANTHER; PTHR11501:SF14; MICROTUBULE-ASSOCIATED PROTEIN TAU; 1.
DR Pfam; PF00418; Tubulin-binding; 1.
DR PROSITE; PS00229; TAU_MAP_1; 1.
DR PROSITE; PS51491; TAU_MAP_2; 1.
PE 4: Predicted;
KW Cytoplasm {ECO:0000256|ARBA:ARBA00022490, ECO:0000256|RuleBase:RU000686};
KW Cytoskeleton {ECO:0000256|ARBA:ARBA00023212,
KW ECO:0000256|RuleBase:RU000686};
KW Microtubule {ECO:0000256|ARBA:ARBA00022701, ECO:0000256|RuleBase:RU000686};
KW Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW Reference proteome {ECO:0000313|Proteomes:UP001488838};
KW Repeat {ECO:0000256|ARBA:ARBA00022737}.
SQ SEQUENCE 110 AA; 11844 MW; E0072CE52AD5321A CRC64;
Query Match 100.0%; Score 77; Length 110;
Best Local Similarity 100.0%;
Matches 17; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SPQLATLADEVSASLAK 17
|||||||||||||||||
Db 91 SPQLATLADEVSASLAK 107
Sequence alignment 2
BET67869
ID BET67869 standard; protein; 54 AA.
XX
AC BET67869;
XX
DT 22-FEB-2018 (first entry)
XX
DE Human tau protein fragment, SEQ 6.
XX
KW Tau protein; antigen; antimicrobial-gen.; cardiovascular disease;
KW cardiovascular-gen.; endocrine disease; endocrine-gen.; genetic disorder;
KW genetic-disease-gen.; growth disorder; growth-disorder-gen.;
KW immune stimulation; infectious disease; metabolic disorder;
KW metabolic-gen.; neurodegenerative disease; neurological disease;
KW neuroprotective; prophylactic to disease; protein production;
KW protein therapy; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2018006092-A1.
XX
CC PD 04-JAN-2018.
XX
CC PF 03-JUL-2017; 2017WO-US040598.
XX
PR 01-JUL-2016; 2016US-0357800P.
PR 29-MAR-2017; 2017US-0478410P.
XX
CC PA (DECL-) DECLION HOLDINGS LLC.
XX
CC PI Zanelli E;
XX
DR WPI; 2018-01137R/08.
XX
CC PT Composition useful for treating protein conformational disorder or
CC PT pathogenic infection, e.g. Alzheimer's disease, Parkinson's disease,
CC PT sickle cell anemia and amyotrophic lateral sclerosis, comprises mixture
CC PT of different polypeptides.
XX
CC PS Disclosure; SEQ ID NO 6; 227pp; English.
XX
CC The present invention relates to an aminoacid copolymer composition
CC comprising a mixture of polypeptides which is useful for treating a
CC protein conformational disorder or a pathogenic infection. The invention
CC also relates to a method for: (a) synthesizing the composition by solid-
CC phase synthesis; (b) eliciting a release of a Th2-associated cytokine or
CC chemokine, and C-C motif chemokine (CCL) 22 from monocytes which involves
CC contacting the monocytes with the composition; (c) eliciting preferential
CC cluster of differentiation (CD) 4 plus T cell proliferation which
CC involves contacting the peripheral blood mononuclear cells with the
CC composition; and (d) generating antibodies that are immunoreactive
CC against the composition of the invention. The invention further relates
CC to a kit comprising the composition and instructions for use in the
CC treatment. The composition of the invention is useful for preventing or
CC treating the protein conformational disorder or the pathogenic infection
CC such as Alzheimer's disease, frontotemporal dementia with parkinsonism
CC linked to chromosome 17 (FTDP-17), Dutch hereditary cerebral hemorrhage
CC with amyloidosis (cerebrovascular amyloidosis), congophilic angiopathy,
CC Pick's disease, familial British dementia, Parkinson's disease, multiple
CC system atrophy, Hallervorden-Spatz disease, amyotrophic lateral
CC sclerosis, Huntington's disease, spinocerebellar ataxia, neuronal
CC intranuclear inclusion disease, hereditary dentatorubral-pallidoluysian
CC atrophy, prion-related diseases (such as scrapie, bovine spongiform
CC encephalopathy, variant CJD, Gerstmann-Straussler-Scheinker syndrome,
CC kuru, fatal familial insomnia, and related disorders), hereditary
CC cystatin c amyloid angiopathy, dementia pugilistica, neurodegenerative
CC diseases (preferably cerebral and nerve atrophy), spinal and bulbar
CC muscular atrophy, familial amyloid polyneuropathy, type-2 diabetes, light
CC chain cast nephropathy, cystic fibrosis, and sickle cell anemia. The
CC composition exhibits an intrinsic adjuvant property that eliminates the
CC need for the addition of a strong adjuvant or a carrier protein for the
CC therapeutic efficacy and decreased risk of neutralizing antibodies which
CC provides no intravenous (IV) administration, and improves the solubility
CC of the composition. The composition is prepared in a cost-effective
CC manner, has satisfactory pharmacokinetic and pharmacodynamic correlation,
CC exhibits ability to target multiple antigenic targets and adaptability
CC across targets and disease indications, and provides sustained
CC immunogenicity. The present sequence is a human tau protein fragment (tau
CC -F) which serves as an antigenic region or a base peptide for treating
CC protein conformational disorders by inducing specific antibodies.
XX
SQ Sequence 54 AA;
Query Match 100.0%; Score 77; Length 54;
Best Local Similarity 100.0%;
Matches 17; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SPQLATLADEVSASLAK 17
|||||||||||||||||
Db 35 SPQLATLADEVSASLAK 51
BET67871
ID BET67871 standard; peptide; 25 AA.
XX
AC BET67871;
XX
DT 22-FEB-2018 (first entry)
XX
DE Human tau protein fragment, SEQ 8.
XX
KW Tau protein; antigen; antimicrobial-gen.; cardiovascular disease;
KW cardiovascular-gen.; endocrine disease; endocrine-gen.; genetic disorder;
KW genetic-disease-gen.; growth disorder; growth-disorder-gen.;
KW immune stimulation; infectious disease; metabolic disorder;
KW metabolic-gen.; neurodegenerative disease; neurological disease;
KW neuroprotective; prophylactic to disease; protein production;
KW protein therapy; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2018006092-A1.
XX
CC PD 04-JAN-2018.
XX
CC PF 03-JUL-2017; 2017WO-US040598.
XX
PR 01-JUL-2016; 2016US-0357800P.
PR 29-MAR-2017; 2017US-0478410P.
XX
CC PA (DECL-) DECLION HOLDINGS LLC.
XX
CC PI Zanelli E;
XX
DR WPI; 2018-01137R/08.
XX
CC PT Composition useful for treating protein conformational disorder or
CC PT pathogenic infection, e.g. Alzheimer's disease, Parkinson's disease,
CC PT sickle cell anemia and amyotrophic lateral sclerosis, comprises mixture
CC PT of different polypeptides.
XX
CC PS Disclosure; SEQ ID NO 8; 227pp; English.
XX
CC The present invention relates to an aminoacid copolymer composition
CC comprising a mixture of polypeptides which is useful for treating a
CC protein conformational disorder or a pathogenic infection. The invention
CC also relates to a method for: (a) synthesizing the composition by solid-
CC phase synthesis; (b) eliciting a release of a Th2-associated cytokine or
CC chemokine, and C-C motif chemokine (CCL) 22 from monocytes which involves
CC contacting the monocytes with the composition; (c) eliciting preferential
CC cluster of differentiation (CD) 4 plus T cell proliferation which
CC involves contacting the peripheral blood mononuclear cells with the
CC composition; and (d) generating antibodies that are immunoreactive
CC against the composition of the invention. The invention further relates
CC to a kit comprising the composition and instructions for use in the
CC treatment. The composition of the invention is useful for preventing or
CC treating the protein conformational disorder or the pathogenic infection
CC such as Alzheimer's disease, frontotemporal dementia with parkinsonism
CC linked to chromosome 17 (FTDP-17), Dutch hereditary cerebral hemorrhage
CC with amyloidosis (cerebrovascular amyloidosis), congophilic angiopathy,
CC Pick's disease, familial British dementia, Parkinson's disease, multiple
CC system atrophy, Hallervorden-Spatz disease, amyotrophic lateral
CC sclerosis, Huntington's disease, spinocerebellar ataxia, neuronal
CC intranuclear inclusion disease, hereditary dentatorubral-pallidoluysian
CC atrophy, prion-related diseases (such as scrapie, bovine spongiform
CC encephalopathy, variant CJD, Gerstmann-Straussler-Scheinker syndrome,
CC kuru, fatal familial insomnia, and related disorders), hereditary
CC cystatin c amyloid angiopathy, dementia pugilistica, neurodegenerative
CC diseases (preferably cerebral and nerve atrophy), spinal and bulbar
CC muscular atrophy, familial amyloid polyneuropathy, type-2 diabetes, light
CC chain cast nephropathy, cystic fibrosis, and sickle cell anemia. The
CC composition exhibits an intrinsic adjuvant property that eliminates the
CC need for the addition of a strong adjuvant or a carrier protein for the
CC therapeutic efficacy and decreased risk of neutralizing antibodies which
CC provides no intravenous (IV) administration, and improves the solubility
CC of the composition. The composition is prepared in a cost-effective
CC manner, has satisfactory pharmacokinetic and pharmacodynamic correlation,
CC exhibits ability to target multiple antigenic targets and adaptability
CC across targets and disease indications, and provides sustained
CC immunogenicity. The present sequence is a human tau protein fragment (tau
CC -F) which serves as an antigenic region or a base peptide for treating
CC protein conformational disorders by inducing specific antibodies.
XX
SQ Sequence 25 AA;
Query Match 100.0%; Score 77; Length 25;
Best Local Similarity 100.0%;
Matches 17; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SPQLATLADEVSASLAK 17
|||||||||||||||||
Db 6 SPQLATLADEVSASLAK 22
BET67873
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BET67873 standard; peptide; 24 AA.
XX
AC BET67873;
XX
DT 22-FEB-2018 (first entry)
XX
DE Human tau protein fragment, SEQ 10.
XX
KW Tau protein; antigen; antimicrobial-gen.; cardiovascular disease;
KW cardiovascular-gen.; endocrine disease; endocrine-gen.; genetic disorder;
KW genetic-disease-gen.; growth disorder; growth-disorder-gen.;
KW immune stimulation; infectious disease; metabolic disorder;
KW metabolic-gen.; neurodegenerative disease; neurological disease;
KW neuroprotective; prophylactic to disease; protein production;
KW protein therapy; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2018006092-A1.
XX
CC PD 04-JAN-2018.
XX
CC PF 03-JUL-2017; 2017WO-US040598.
XX
PR 01-JUL-2016; 2016US-0357800P.
PR 29-MAR-2017; 2017US-0478410P.
XX
CC PA (DECL-) DECLION HOLDINGS LLC.
XX
CC PI Zanelli E;
XX
DR WPI; 2018-01137R/08.
XX
CC PT Composition useful for treating protein conformational disorder or
CC PT pathogenic infection, e.g. Alzheimer's disease, Parkinson's disease,
CC PT sickle cell anemia and amyotrophic lateral sclerosis, comprises mixture
CC PT of different polypeptides.
XX
CC PS Example 1; SEQ ID NO 10; 227pp; English.
XX
CC The present invention relates to an aminoacid copolymer composition
CC comprising a mixture of polypeptides which is useful for treating a
CC protein conformational disorder or a pathogenic infection. The invention
CC also relates to a method for: (a) synthesizing the composition by solid-
CC phase synthesis; (b) eliciting a release of a Th2-associated cytokine or
CC chemokine, and C-C motif chemokine (CCL) 22 from monocytes which involves
CC contacting the monocytes with the composition; (c) eliciting preferential
CC cluster of differentiation (CD) 4 plus T cell proliferation which
CC involves contacting the peripheral blood mononuclear cells with the
CC composition; and (d) generating antibodies that are immunoreactive
CC against the composition of the invention. The invention further relates
CC to a kit comprising the composition and instructions for use in the
CC treatment. The composition of the invention is useful for preventing or
CC treating the protein conformational disorder or the pathogenic infection
CC such as Alzheimer's disease, frontotemporal dementia with parkinsonism
CC linked to chromosome 17 (FTDP-17), Dutch hereditary cerebral hemorrhage
CC with amyloidosis (cerebrovascular amyloidosis), congophilic angiopathy,
CC Pick's disease, familial British dementia, Parkinson's disease, multiple
CC system atrophy, Hallervorden-Spatz disease, amyotrophic lateral
CC sclerosis, Huntington's disease, spinocerebellar ataxia, neuronal
CC intranuclear inclusion disease, hereditary dentatorubral-pallidoluysian
CC atrophy, prion-related diseases (such as scrapie, bovine spongiform
CC encephalopathy, variant CJD, Gerstmann-Straussler-Scheinker syndrome,
CC kuru, fatal familial insomnia, and related disorders), hereditary
CC cystatin c amyloid angiopathy, dementia pugilistica, neurodegenerative
CC diseases (preferably cerebral and nerve atrophy), spinal and bulbar
CC muscular atrophy, familial amyloid polyneuropathy, type-2 diabetes, light
CC chain cast nephropathy, cystic fibrosis, and sickle cell anemia. The
CC composition exhibits an intrinsic adjuvant property that eliminates the
CC need for the addition of a strong adjuvant or a carrier protein for the
CC therapeutic efficacy and decreased risk of neutralizing antibodies which
CC provides no intravenous (IV) administration, and improves the solubility
CC of the composition. The composition is prepared in a cost-effective
CC manner, has satisfactory pharmacokinetic and pharmacodynamic correlation,
CC exhibits ability to target multiple antigenic targets and adaptability
CC across targets and disease indications, and provides sustained
CC immunogenicity. The present sequence is a human tau protein fragment (tau
CC -F) which serves as an antigenic region or a base peptide treating
CC protein conformational disorders by inducing specific antibodies.
XX
SQ Sequence 24 AA;
Query Match 100.0%; Score 77; Length 24;
Best Local Similarity 100.0%;
Matches 17; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SPQLATLADEVSASLAK 17
|||||||||||||||||
Db 5 SPQLATLADEVSASLAK 21