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(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date (10) International Publication Number 29 March 2012 (29.03.2012) (51) International Patent Classification: C07K 7/08 (2006.01) A61P 7/00 (2006.01) A61K 38/10 (2006.01) (21) International Application Number: PO PCT WO 2012/040259 A 3 PCT/US201 1/052442 (22) International Filing Date: 2 1 September 201 1 (21 .09.201 1) (25) Filing Language: (26) Publication Language: (30) Priority Data: 61/385,71 1 2 3 September 2010 (23.09.2010) English English US (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind o regional protection available): ARIPO (BW, GH, f GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG). Published: (71) Applicants (for all designated States except US): THE UNIVERSITY OF TRUSTEES OF THE PENNSYLVANIA [US/US]; Center For Technology Transfer, 3 1 60 Chestnut Street. Suite 200, Philadelphia, Pennsylvania 19104 (US). THE BOARD O F TRUSTEES O F THE UNIVERSITY O F ILLINOIS [US/US]; 352 Henry Administration Building, 506 South Wright Street, Urbana, Illinois 61801 (US). — (72) Inventors; and (75) Inventors/ Applicants (for US only): LAMBRIS, John D . — [US/US]; 630 Pine Street, Philadelphia, Pennsylvania 19106 (US). VAN DER DONK, Wilfred A . [NL/US]; 3204 Cherry Hills Drive, Champaign, Illinois 6 1 822 (US). (88) (74) Agents: REED, Janet E . et al; Potter Anderson & Corroon LLP, P.O. Box 9 5 1, 13 13 N . Market Street, W ilm in g ton, Delaware 19899-095 1 (US). with international search report (Art. 21(3)) before the expiration of the time limit for amending the claims and to be republished in the event of receipt o f amendments (Rule 48.2(h)) Date of publication of the international search report: 3 1 May 2012 < * o © o (54) Title: MODIFIED COMPSTATIN WITH IMPROVED STABILITY AND BINDING PROPERTIES (57) Abstract: Compounds comprising peptides capable o f binding C 3 protein and inhibiting complement activation are disclosed. These cyclic compounds are modified t o improve stability while maintaining substantially equivalent complement activation-inhibit ory activity a s compared with currently available compounds. The compounds comprise compstatin analogs in which the disulfide bond between C 2 and C12 i s modified via a thioether bond t o form a cystathionine. INTERNATIONAL SEARCH REPORT International application No PCT/US2011/052442 A . CLASSIFICATION O F SUBJECT MATTER C07K7/Q8 A61P7/0O A61K38/10 According to International Patent Classification (IPC) o r t o both national classification and IPC B . FIELDS SEARCHED Minimum documentation searched (classification system followed by classification symbols C07K A61K Documentation searched other than minimum documentation t o the extent that such documents are included in the fields searched Electronic data base consulted during the international search (name of data base and, where practical, search terms used) EPO-Internal BIOSIS, EMBASE, WPI Data C . DOCUMENTS Category* CONSIDERED T O B E RELEVANT Relevant to claim No. Citation o f document, with indication, where appropriate, of the relevant passages WO 2007/O62249 A2 (UNIV PENNSYLVANIA [US] LAMBRIS JOHN D [US] ; KATRAGADDA MADAN [US] ) 3 1 May 2 7 (2007-05-31) l i ne 1-24 pp. 3-5, paragraph "Summary o f the i nvention" , p . 1 1 , Table 1 - p . 19, 2 , c l aims 1-25 RICKLIN DANI E L ET AL: "Compstati n : a compl ement inhibi tor o n i t s way t o c l ini cal appl i cati on" , ADVANCES I N EXPERIMENTAL MEDICINE AND BIOLOGY, SPRINGER, US, vol . 632 , 1 January 2008 (2008-01-01) , pages 273-292 , XP002588971, ISSN : 0065-2598 ISBN : 978-0-387-69078-0 the whole document 1-24 Further documents are listed i n the continuation of Box C . * Special categories of cited documents : See patent family annex. "T" later document published after the international filing date "A" document defining the general state of the art which is not considered to b e of particular relevance "E" earlier document but published o n o r after the international filing date "L" document which may throw doubts o n priority claim(s) o r which is cited t o establish the publication date of another o r priority date and not in conflict with the application but cited to understand the principle o r theory underlying the invention "X" document of particular relevance; the claimed invention cannot be considered novel o r cannot b e considered to involve a n inventive step when the document is taken alone citation o r other special reason (as specified) "O" document referring t o a n oral disclosure, use, exhibition o r other means "P" document published prior t o the international filing date but " document of particular relevance; the claimed invention cannot be considered to involve a n inventive step when the document is combined with one o r more other such docu¬ ments, such combination being obvious t o a person skilled in the art. "&" document member of the same patent family later than the priority date claimed Date of the actual completion of the international search Date of mailing of the international search report 4 Apri l 2012 Name and mailing address of the ISA/ European Patent Office, P.B. 5818 Patentlaan 2 N L - 2280 HV Rijswijk Tel. (+31-70) 340-2040, Fax: (+31-70) 340-3016 18/04/2012 Authorized officer R. von Eggel kraut-G. INTERNATIONAL SEARCH REPORT International application No PCT/US2011/052442 C(Continuation). Category * DOCUMENTS CONSIDERED T O B E RELEVANT Relevant t o claim No. Citation of document, with indication, where appropriate, of the relevant passages Y WO 2008/153963 A l (UNIV PENNSYLVANIA [US] ; BIJVOET CT FOR BI0M0LECULAR R E [NL] ; LAMBRIS J ) 18 December 2008 (2008-12-18) page 7 - page 2 0 "Conformati o n o f L-cystathi oni ne, a carba anal o g o f cysti ne, and stereochemi stry o f hormone-receptor i nteracti ons" , BIOCHIMICA ET BIOPHYSICA ACTA - GENERAL SUBJECTS, ELSEVI E R SCI ENCE PUBLISHERS, NL, vol . 538, no. 3 , 1 February 1978 (1978-02-01) , pages 534-540, XP023494772 , ISSN : 0304-4165, D0I : 10. 1016/0304-4165 (78)90414-2 [retri eved o n 1978-02-01] abstract, p . 538, last paragraph - p . 539 , l i ne 2 CHENG-SAN CHEN ET AL: 1-24 Y 1-24 Y "Thioether s i d e chain cycl i zati o n for hel i cal pepti d e formation : i nhibi tors o f estrogen receptor-coacti vator i nteracti ons . " , THE JOURNAL O F PEPTIDE RESEARCH : OFFICIAL JOURNAL O F THE AMERICAN PEPTIDE SOCI ETY MAR 2004 LNKD- PUBMED: 15049842, vol . 63, no. 3 , March 2004 (2004-03) , pages 297-302 , XP002670830, ISSN : 1397-002X abstract HIDAKA Y ET AL: "Synthesi s and b i ologi cal properties o f carba-analogs o f heat-stabl e enterotoxi n (ST) produced by enterotoxi geni c Escheri chi a col i " , BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, ACADEMIC PRESS INC. ORLANDO, FL, US, vol . 176, no. 3 , 15 May 1991 (1991-05-15) , pages 958-965 , XP024835891, ISSN : 0006-291X, DOI : 10. 1O16/O0O6-291X(91)9O375-H [retri eved o n 1991-05-15] the whole document GALANDE A K ET AL: 1-24 Y 1-24 -/-- INTERNATIONAL SEARCH REPORT International application No PCT/US2011/052442 C(Continuation). Category * DOCUMENTS CONSIDERED T O B E RELEVANT Relevant t o claim No. Citation of document, with indication, where appropriate, of the relevant passages Y MOLL G N ET AL: " A b i ologi cal stabi i zation technol ogy for pepti d e drugs : enzymati c i ntroduction of thioether-bri dges" , DRUG DISCOVERY TODAY: TECHNOLOGI ES, ELSEVI ER, vol . 6 , no. 1-4, 1 January 2009 (2009-01-01) , pages E13-E18, XP027148568, ISSN : 1740-6749 [retri eved o n 2009-04-19] the whole document 1-24 X, P KNERR PATRICK J ET AL: "Synthesi s and activi t y o f thioether-containi n g anal ogues o f the complement inhi b i tor compstati n . " , ACS CHEMICAL BIOLOGY 15 JUL 2011 LNKDPUBMED.21520911, vol . 6 , no. 7 , 15 July 2011 (2011-07-15) , pages 753-760, XP002670831, ISSN : 1554-8937 the whole document 1-24 International application No. INTERNATIONAL SEARCH REPORT Box No. I I PCT/US20 1 1/052442 Observations where certain claims were found unsearchable (Continuation of item 2 of first sheet) This international search report has not been established in respect o f certain claims under Article (2) (a) for the following reasons: □ Claims Nos.: because they relate t o subject matter not required t o be searched by this Authority, namely: Claims Nos.: because they relate t o parts of the international application that d o not comply with the prescribed requirements t o such a n extent that n o meaningful international search can be carried out, specifically: F U RTH E R I NFORMATI O N sheet PCT/ I SA/2 1Q □ Claims Nos.: because they are dependent claims and are not drafted i n accordance with the second and third sentences of Rule 6.4(a). Box No. Ill Observations where unity of invention is lacking (Continuation of item 3 of first sheet) This International Searching Authority found multiple inventions i n this international application, as follows: □ i aims. A s all required additional search fees were timely paid by the applicant, this international search report covers all searchable 2. I I As all searchable claims could be searched without effort justifying a n additional fees, this Authority did not invite payment of additional fees. 3. ' A s only some o f the required additional search fees were timely paid by the applicant, this international search report covers ' only those claims for which fees were paid, specifically claims Nos. : 4. I I No required additional search fees were timely paid by the applicant. Consequently, this international search report is restricted to the invention first mentioned in the claims; it is covered by claims Nos.: Remark o n Protest ' ' The additional search fees were accompanied by the applicant's protest and, where applicable, the ' payment o f a protest fee. The additional search fees were accompanied by the applicant's protest but the applicable protest ' fee was not paid within the time limit specified i n the invitation. I INo protest accompanied the payment of additional search fees. Form PCT/ISA/21 0 (continuation of first sheet (2)) (April 2005) International Application No. PCTV US2011/ Q52442 FURTHER INFORMATION CONTINUED FROM PCT/ISA/ 210 Continuati o n o f Box 11 . 25 Cl aims Nos. : Present c l aim 2 5 encompasses compounds defined only by thei r desi red functi on, contrary t o the requi rements of clari t y of Arti cle 6 PCT, because the resul t-to-be-achieved type of defi n i t i o n does not a l low the scope of the claim t o b e ascertained. The fact that any compound could b e screened does not overcome thi s objection , a s the ski l led person would not have knowl edge beforehand a s t o whether i t would fal l wi thin the scope claimed. Undue experimentati o n would b e requi red t o screen compounds randomly. The appl i cant ' s attention i s drawn t o the fact that c l aims rel ating t o inventions i n respect of whi c h n o international search report has been establ i shed need not b e the subject of a n international prel iminary examination (Rule 66. 1(e) PCT) . The appl i cant i s advi sed that the EPO pol i cy when acting a s a n Internati onal Prel imi nary Examini n g Authori t y i s normal l y not t o carry out a prel iminary examination o n matter whi c h has not been searched. Thi s i s the case i rrespecti v e of whether or not the c l aims are amended fol lowi n g recei pt of the search report or during any Chapter I I procedure. I f the appl i cati o n proceeds into the regional phase before the EPO, the appl i cant i s reminded that a search may b e carried out during examination before the EPO (see EPO Gui del i n e C-VI , 8.2) , should the problems whi c h led t o the Arti cle 17(2) declaration be overcome. INTERNATIONAL SEARCH REPORT Information o n patent family members International application No PCT/US2011/052442 Patent family member(s) Publication date Patent document cited in search report WO Publication date 2007062249 A2 31-05-2007 AU BR CA CN EP EP EP P US US O 2006318333 PI0619Q23 2631443 101400692 1960422 2377877 2377878 2009517476 2008227717 2012004393 2007062249 Al A2 Al A A2 Al Al A Al Al A2 31-05-2007 20-09-2011 31-05-2007 01-04-2009 27-08-2008 19-10-2011 19-10-2011 30-04-2009 18-09-2008 05-01-2012 31-05-2007 10-03-2011 18-12-2008 W0 2008153963 Al 18-12-2008 US W0 2011060127 Al 2008153963 Al