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WO 2014/089124 Al 12 June 20 14 ( 12.06.20 14) W P O P C T

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WO 2014/089124 Al 12 June 20 14 ( 12.06.20 14) W P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2014/089124 Al 12 June 20 14 ( 12.06.20 14) W P O P C T (51) International Patent Classification: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, A61K 48/00 (2006.01) A61P 37/00 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, A61K 39/395 (2006.01) HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, (21) International Application Number: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, PCT/US2013/072938 OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (22) International Filing Date: SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, 3 December 2013 (03.12.2013) TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of regional protection available): ARIPO (BW, GH, (30) Priority Data: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, 61/732,746 3 December 2012 (03. 12.2012) US UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 61/747,653 31 December 2012 (3 1. 12.2012) US TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, ΓΓ, LT, LU, LV, (71) Applicants: CENEXYS, INC. [US/US]; 1700 Owens MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, Street, Suite 535, San Francisco, California 941 58 (US). TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KYTHERA BIOPHARMCEUTICALS, INC. [US/US]; KM, ML, MR, NE, SN, TD, TG). 27200 West Agoura Road, Suite 200, Calabasas, California 91301 (US). BUCK INSTITUTE FOR RESEARCH ON Declarations under Rule 4.17: AGING [US/US]; 8001 Redwood Boulevard, Novate, — as to applicant's entitlement to apply for and be granted a California 94945 (US). patent (Rule 4.1 7(H)) (72) Inventors: VASSEROT, Alain Philippe; 6421 La Paloma — as to the applicant's entitlement to claim the priority of the Street, Carlsbad, California 92009 (US). LICHTSTEIN- earlier application (Rule 4.1 7(in)) ER, Serge; 1252 Brookview Avenue, Westlake Village, Published: California 91361 (US). CAMPISI, Judith; 1 Roble Road, Berkeley, California 94705 (US). — with international search report (Art. 21(3)) (74) Agents: ROSOK, Mae, Joanne et al; Seed Intellectual — before the expiration of the time limit for amending the Property Law Group PLLC, Suite 5400, 701 Fifth Avenue, claims and to be republished in the event of receipt of Seattle, Washington 98104-7064 (US). amendments (Rule 48.2(h)) (81) Designated States (unless otherwise indicated, for every — with sequence listing part of description (Rule 5.2(a)) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (54) Title: IMMUNOGENIC COMPOSITIONS FOR INDUCING AN IMMUNE RESPONSE FOR ELIMINATION OF SENES CENT CELLS (57) Abstract: Provided herein are immunogenic compositions (vaccines) and methods for immunizing a subject with the immuno genic compositions for inducing an adaptive immune response directed specifically against senescent cells for treatment and prophy laxis of age-related diseases and disorders, and other diseases and disorders associated with or exacerbated by the presence of senes - cent cells. The immunogenic compositions provided herein comprise at least one or more senescent cell-associated antigens, poly nucleotides encoding senescent cell-associated antigens, and recombinant expression vectors comprising the polynucleotides for use in administering to a subject in need thereof. IMMUNOGENIC COMPOSITIONS FOR INDUCING AN IMMUNE RESPONSE FOR ELIMINATION OF SENESCENT CELLS STATEMENT REGARDING SEQUENCE LISTING The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification. The name of the text file containing the Sequence Listing is 200201_412WO_SEQUENCE_LISTING.txt. The text file is 1 KB, was created on December 3, 2013 and is being submitted electronically via EFS-Web. BACKGROUND Technical Field The disclosure herein relates generally to immunogenic compositions (e.g., vaccines) and methods for using the immunogenic compositions for inducing an immune response directed specifically against senescent cells for treatment and prophylaxis of age-related diseases and disorders, and other diseases and disorders associated or exacerbated by the presence of senescent cells. Description of the Related Art Senescent cells accumulate in tissues and organs of individuals as they age and are found at sites of age-related pathologies. While senescent cells are believed important to inhibiting proliferation of dysfunctional or damaged cells and particularly to constraining development of malignancy (see, e.g., Campisi, Curr. Opin. Genet. Dev. 21:107-12 (201 1); Campisi, Trends Cell Biol. 11:S27-31 (2001); Prieur et al, Curr. Opin. Cell Biol. 20:150-55 (2008)), the presence of senescent cells in an aging individual may contribute to aging and aging-related dysfunction (see, e.g., Campisi, Cell 120:5 13-22 (2005)). Given that senescent cells have been causally implicated in certain aspects of age-related decline in health and may contribute to certain diseases, and are also induced as a result of necessary life-preserving chemotherapeutic and radiation treatments, the presence of senescent cells may have deleterious effects to millions of patients worldwide (e.g., fatigue, weakness, loss of physical agility, decrease in cognitive function). Accordingly, treatments aimed at clearing aging- induced and therapy-induced senescent cells and improving age-sensitive traits have the potential to markedly improve the health, lifespan, and quality of life for patients exposed to senescence-inducing stimuli. The present disclosure addresses these needs and offers numerous related advantages. BRIEF SUMMARY Disclosed herein are immunogenic compositions and methods of using the compositions for inducing an immune response that is specific for senescent cells (i.e., specific for senescent cell associated antigens expressed by the senescent cells) and that comprises clearance (i.e., removal, elimination) of senescent cells from the subject receiving the immunogenic composition. The methods include active and passive immunization. Provided herein are the following embodiments. In one embodiment, a method is provided for evoking an immune response specific for a senescent cell in a subject, wherein the immune response comprises clearance of the senescent cell by the immune system of the subject, wherein the method comprises administering to the subject an immunogenic composition comprising: (a) a pharmaceutically acceptable excipient, and (b) an immunogen. In particular embodiments, the immunogen is selected from (i) an isolated senescent cell- associated antigen or an antigenic fragment thereof, wherein the senescent cell- associated antigen is selected from (A) pl6INK4a, (B) a senescent cell-associated antigen selected from Table 1, and (C) a senescent cell-associated antigen that is encoded by a nucleic acid sequence selected from Table 2 or Table 3, and wherein the antigenic fragment comprises at least 20 contiguous amino acids of the senescent cell- associated antigen; (ii) an isolated polynucleotide encoding at least two senescent cell- associated antigens of (i) or antigenic fragments thereof; (iii) at least two isolated polynucleotides, wherein a first isolated polynucleotide encodes a first senescent cell- associated antigen or an antigenic fragment thereof, and wherein the first senescent cell- associated antigen is selected from (A) pl6INK4a, (B) a senescent cell-associated antigen selected from Table 1, and (C) a senescent cell-associated antigen that is encoded by a nucleic acid sequence selected from Table 2 or Table 3, and wherein the antigenic fragment comprises at least 20 contiguous amino acids of the first senescent cell-associated antigen, and a second polynucleotide encodes a second senescent cell- associated antigen, wherein the second senescent cell-associated antigen is selected from (A) pl6INK4a, (B) a senescent cell-associated antigen selected from Table 1, and (C) a senescent cell-associated antigen that is encoded by a nucleic acid sequence selected from Table 2 or Table 3, and wherein the antigenic fragment comprises at least 20 contiguous amino acids of the second senescent cell-associated antigen; (iv) a recombinant expression vector that is a viral vector comprising a polynucleotide that encodes the senescent cell-associate antigen or antigenic fragment thereof of (i); (v) a senescent cell membrane preparation, a senescent cell organelle preparation, or an exosome; (vi) a fusion polypeptide comprising at least two senescent cell-associated antigens, wherein each of the at least two senescent cell-associated antigens are different and each is selected from (A) pl6INK4a, (B) a senescent cell-associated antigen selected from Table 1, and (C) a senescent cell-associated antigen that is encoded by a nucleic acid sequence selected from Table 2 or Table 3; (vii) a fusion polypeptide comprising at least two antigenic fragments wherein each of the at least two antigenic fragments comprises at least 20 contiguous amino acids of a senescent cell-associated antigen selected from (A) pl6INK4a, (B) a senescent cell-associated antigen selected from Table 1, and (C) a senescent
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