Lectin-like oxidized LDL receptor 1 antibodies and methods of use

Heldwein, Kurt Alex ; Brogdon, Jennifer ; et al.

2017

Online Patent

Zugriff:

Diesen Eintrag von USPTO Patent Grants anschauen (Volltext)

The present invention relates to monoclonal antibodies binding to human lectin-like oxidized LDL (low density lipoprotein) receptor 1 (hereinafter, sometimes referred to as “LOX-1”), and pharmaceutical compositions and methods of treatment comprising the same.

Titel:	Lectin-like oxidized LDL receptor 1 antibodies and methods of use
Autor/in / Beteiligte Person:	Heldwein, Kurt Alex ; Brogdon, Jennifer ; Dole, William ; Trauger, John ; Tang, Yuting ; Neugebauer, Julia ; Schmid, Annika
Link:	Diesen Eintrag von USPTO Patent Grants anschauen (Volltext)
Veröffentlichung:	2017
Medientyp:	Patent
Sonstiges:	Nachgewiesen in: USPTO Patent Grants Sprachen: English Patent Number: 9,562,101 Publication Date: February 07, 2017 Appl. No: 14/307519 Application Filed: June 18, 2014 Assignees: NOVARTIS AG (Basel, CH) Claim: 1. An isolated antibody or antigen binding fragment thereof that binds human lectin-type oxidized low density lipoprotein receptor 1 (LOX-1), comprising a variable heavy chain (VH) comprising the amino acid sequence of SEQ ID NO: 309; and a variable light chain (VL) comprising the amino acid sequence of SEQ ID NO: 319. Claim: 2. The antibody or fragment of claim 1 , which comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 311 and a light chain comprising the amino acid sequence of SEQ ID NO: 321. Claim: 3. The antibody of claim 1 , which is a monoclonal antibody. Claim: 4. The antibody of claim 1 , which is a human antibody. Claim: 5. A pharmaceutical composition comprising the antibody or fragment of claim 1 and a pharmaceutically acceptable carrier. Claim: 6. An isolated antibody or antigen binding fragment thereof that binds human LOX-1, comprising a heavy chain variable region (VH) comprising complementarity determining regions HCDR1, HCDR2, and HCDR3 and a light chain variable region (VL) comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 303; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 304; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 305; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 313; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 314; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 315. Claim: 7. The antibody or fragment of claim 6 , wherein the VH comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 309, and wherein the VL comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 319. Claim: 8. The antibody or fragment of claim 6 , wherein the VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 309, and wherein the VL comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 319. Claim: 9. The antibody or fragment of claim 6 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 309. Claim: 10. The antibody or fragment of claim 6 , wherein the VL comprises the amino acid sequence of SEQ ID NO: 319. Claim: 11. The antibody of claim 6 , which is a monoclonal antibody. Claim: 12. The antibody of claim 6 , which is a human antibody. Claim: 13. The antibody or fragment of claim 6 , which is a single chain antibody, Fab fragment, Fv fragment, F(ab)2 fragment, or scFv fragment. Claim: 14. The antibody or fragment of claim 6 , which is an IgG1 isotype. Claim: 15. A pharmaceutical composition comprising the antibody or fragment of claim 6 and a pharmaceutically acceptable carrier. Claim: 16. An isolated antibody or antigen binding fragment thereof, comprising a heavy chain variable region (VH) comprising complementarity determining regions HCDR1, HCDR2, and HCDR3, and a light chain variable region (VL) comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 306; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 307; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 308; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 316; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 317; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 318. Claim: 17. The antibody or fragment of claim 16 , wherein the VH comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 309, and wherein the VL comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 319. Claim: 18. The antibody or fragment of claim 16 , wherein the VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 309, and wherein the VL comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 319. Claim: 19. The antibody or fragment of claim 16 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 309. Claim: 20. The antibody or fragment of claim 16 , wherein the VL comprises the amino acid sequence of SEQ ID NO: 319. Claim: 21. The antibody of claim 16 , which is a monoclonal antibody. Claim: 22. The antibody of claim 16 , which is a human antibody. Claim: 23. The antibody or fragment of claim 16 , which is a single chain antibody, Fab fragment, Fv fragment, F(ab)2 fragment, or scFv fragment. Claim: 24. The antibody or fragment of claim 6 , which is an IgG1 isotype. Claim: 25. A pharmaceutical composition comprising the antibody or fragment of claim 16 and a pharmaceutically acceptable carrier. Claim: 26. An isolated antibody or antigen binding fragment thereof that binds human LOX-1, comprising a heavy chain variable region (VH) comprising complementarity determining regions HCDR1, HCDR2, and HCDR3, and a light chain variable region (VL) comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein: (i) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 3; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 4; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 5; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 15; (ii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 23; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 24; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 25; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 33; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 34; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 35; (iii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 43; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 44; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 45; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 53; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 54; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 55; (iv) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 63; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 64; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 65; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 73; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 74; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 75; (v) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 83; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 84; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 85; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 93; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 94; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 95; (vi) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 103; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 104; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 105; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 113; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 114; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 115; (vii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 123; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 124; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 125; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 133; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 134; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 135; (viii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 143; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 144; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 145; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 153; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 154; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 155; (ix) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 163; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 164; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 165; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 173; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 174; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 175; (x) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 183; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 184; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 185; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 193; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 194; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 195; (xi) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 203; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 204; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 205; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 213; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 214; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 215; (xii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 223; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 224; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 225; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 233; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 234; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 235; (xiii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 243; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 244; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 245; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 253; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 254; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 255; (xiv) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 263; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 264; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 265; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 273; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 274; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 275; (xv) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 283; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 284; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 285; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 293; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 294; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 295; (xvi) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 303; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 304; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 305; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 313; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 314; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 315; (xvii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 323; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 324; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 325; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 333; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 334; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 335; (xviii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 343; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 344; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 345; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 353; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 354; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 355; (xix) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 363; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 364; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 365; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 373; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 374; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 375; (xx) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 6; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 7; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 8; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 16; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 17; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 18; (xxi) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 26; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 27; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 28; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 36; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 37; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 38; (xxii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 46; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 47; the HCDR3 comprises the amino acid sequence of SEQ ID NO:48; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 56; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 57; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 58; (xxiii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 66; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 67; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 68; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 76; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 77; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 78; (xxiv) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 86; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 87; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 88; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 96; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 97; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 98; (xxv) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 106; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 107; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 108; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 116; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 117; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 118; (xxvi) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 126; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 127; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 128; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 136; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 137; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 138; (xxvii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 146; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 147; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 148; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 156; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 157; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 158; (xxviii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 166; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 167; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 168; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 176; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 177; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 178; (xxix) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 186; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 187; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 188; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 196; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 197; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 198; (xxx) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 206; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 207; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 208; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 216; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 217; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 218; (xxxi) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 226; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 227; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 228; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 236; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 237; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 238; (xxxii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 246; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 247; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 248; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 256; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 257; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 258; (xxxiii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 266; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 267; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 268; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 276; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 277; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 278; (xxxiv) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 286; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 287; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 288; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 296; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 297; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 298; (xxxv) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 306; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 307; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 308; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 316; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 317; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 318; (xxxvi) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 326; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 327; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 328; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 336; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 337; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 338; (xxxvii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 346; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 347; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 348; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 356; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 357; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 358; or (xxxviii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 366; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 367; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 368; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 376; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 377; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 378. Claim: 27. The antibody or antigen binding fragment of claim 26 , wherein: (i) the VH comprises the amino acid sequence of SEQ ID NO: 9, and the VL comprises the amino acid sequence of SEQ ID NO: 19; (ii) the VH comprises the amino acid sequence of SEQ ID NO: 29, and the VL comprises the amino acid sequence of SEQ ID NO: 39; (iii) the VH comprises the amino acid sequence of SEQ ID NO: 49, and the VL comprises the amino acid sequence of SEQ ID NO: 59; (iv) the VH comprises the amino acid sequence of SEQ ID NO: 69, and the VL comprises the amino acid sequence of SEQ ID NO: 79; (v) the VH comprises the amino acid sequence of SEQ ID NO: 89, and the VL comprises the amino acid sequence of SEQ ID NO: 99; (vi) the VH comprises the amino acid sequence of SEQ ID NO: 109, and the VL comprises the amino acid sequence of SEQ ID NO: 119; (vii) the VH comprises the amino acid sequence of SEQ ID NO: 129, and the VL comprises the amino acid sequence of SEQ ID NO: 139; (viii) the VH comprises the amino acid sequence of SEQ ID NO: 149, and the VL comprises the amino acid sequence of SEQ ID NO: 159; (ix) the VH comprises the amino acid sequence of SEQ ID NO: 169, and the VL comprises the amino acid sequence of SEQ ID NO: 179; (x) the VH comprises the amino acid sequence of SEQ ID NO: 189, and the VL comprises the amino acid sequence of SEQ ID NO: 199; (xi) the VH comprises the amino acid sequence of SEQ ID NO: 209, and the VL comprises the amino acid sequence of SEQ ID NO: 219; (xii) the VH comprises the amino acid sequence of SEQ ID NO: 229, and the VL comprises the amino acid sequence of SEQ ID NO: 239; (xiii) the VH comprises the amino acid sequence of SEQ ID NO: 249, and the VL comprises the amino acid sequence of SEQ ID NO: 259; (xiv) the VH comprises the amino acid sequence of SEQ ID NO: 269, and the VL comprises the amino acid sequence of SEQ ID NO: 279; (xv) the VH comprises the amino acid sequence of SEQ ID NO: 289, and the VL comprises the amino acid sequence of SEQ ID NO: 299; (xvi) the VH comprises the amino acid sequence of SEQ ID NO: 309, and the VL comprises the amino acid sequence of SEQ ID NO: 319; (xvii) the VH comprises the amino acid sequence of SEQ ID NO: 329, and the VL comprises the amino acid sequence of SEQ ID NO: 339; (xviii) the VH comprises the amino acid sequence of SEQ ID NO: 349, and the VL comprises the amino acid sequence of SEQ ID NO: 359; or (xix) the VH comprises the amino acid sequence of SEQ ID NO: 369, and the VL comprises the amino acid sequence of SEQ ID NO: 379. Patent References Cited: 6197937 March 2001 Sawamura et al. ; 7993643 August 2011 Kobayashi et al. ; 2008/0152657 June 2008 Horowitz et al. ; 2012/0087926 April 2012 Matsuda ; 2014/0377281 December 2014 Heldwein et al. ; 2015/0004168 January 2015 Heldwein et al. ; 1 418 234 May 2004 ; 2 048 161 April 2009 ; 2 444 492 April 2012 ; 2012/009709 January 2012 ; 2014/205300 December 2014 ; 2014/205302 December 2014 Other References: Sakamoto et al, 2009. J Cell Physiol. 220:706-715. cited by examiner ; Tickle et al, 2009. JALA. 14:303-307. cited by examiner ; Rudikoff et al (Proc Natl Acad Sci USA 1982 vol. 79 pp. 1979-1983). cited by examiner ; MacCallum et al. (Journal of Molecular. Biology, 1996, vol. 262, pp. 732-745). cited by examiner ; Pascalis et al (Journal of Immunology, 2002, vol. 169, pp. 3076-3084). cited by examiner ; Casset et al (Biochemical and Biophysical Research Communications, 2003, vol. 307, pp. 198-205. cited by examiner ; Vajdos et al (Journal of Molecular biology, 2002, vol. 320, pp. 415-428). cited by examiner ; Holm et al (Molecular Immunology, 2007, vol. 44, pp. 1075-1084). cited by examiner ; Chen et al. (Journal of Molecular Biology, 1999, vol. 293, pp. 865-881). cited by examiner ; Wu et al. (Journal of Molecular Biology, 1999, vol. 294, pp. 151-162). cited by examiner ; Brown et al., Tolerance of single, but not multiple, amino acid replacements in antibody VH CDR 2: a means of minimizing B cell wastage from somatic hypermutation? J Immunol. May 1, 1996;156(9):3285-91. cited by applicant ; Ohki et al., Crystal structure of human lectin-like, oxidized low-density lipoprotein receptor 1 ligand binding domain and its ligand recognition mode to OxLDL. Structure. Jun. 2005;13(6):905-17. cited by applicant ; Wark et al., Latest technologies for the enhancement of antibody affinity. Adv Drug Deliv Rev. Aug. 7, 2006;58(5-6):657-70. cited by applicant ; Xu et al., Anti-LOX-1 rescues endothelial function in coronary arterioles in atherosclerotic ApoE knockout mice. Arterioscler Thromb Vasc Biol. Apr. 2007;27(4):871-7. cited by applicant Primary Examiner: Howard, Zachary Attorney, Agent or Firm: Le, Hong-Van M.

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