Bispecific anti-vegf and anti-trkb binding molecules for the treatment of eye diseases
AssigneeBoehringer Ingelheim International GmbH
InventorsPeter Michael BENZ, Remko Alexander BAKKER, Holger FUCHS, Fei HAN, Sandeep KUMAR, Sarah LOW, Justin M. SCHEER, Leo THOMAS
Life of this patent
Estimating the term…
Abstract
This invention relates to binding molecules that bind specifically Vascular Endothelial Growth Factor (VEGF) and Tropomyosin receptor kinase B (TrkB) and their use in medicine, pharmaceutical compositions comprising the same, and methods of using the same as agents for treatment and/or prevention of diseases of the eye.
Claims39
A binding molecule comprising at least one antigen binding site that binds specifically to Vascular Endothelial Growth Factor (VEGF) and at least one antigen binding site that binds specifically to Tropomyosin receptor kinase B (TrkB).
A binding molecule comprising a light chain comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or at least 99% identical to the amino acid sequence of SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141 or 143, and a heavy chain comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or at least 99% identical to the amino acid sequence of SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102,104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136, 138, 140, 142, or 144.
A binding molecule comprising:
- (i) a light chain comprising the amino acid sequence of SEQ ID NO:41 and a heavy chain comprising the amino acid sequence of SEQ ID NO:42, or (ii) a light chain comprising the amino acid sequence of SEQ ID NO:43 and a heavy chain comprising the amino acid sequence of SEQ ID NO:44, or (iii) a light chain comprising the amino acid sequence of SEQ ID NO:45 and a heavy chain comprising the amino acid sequence of SEQ ID NO:46, or (iv) a light chain comprising the amino acid sequence of SEQ ID NO:47 and a heavy chain comprising the amino acid sequence of SEQ ID NO:48, or (v) a light chain comprising the amino acid sequence of SEQ ID NO:49 and a heavy chain comprising the amino acid sequence of SEQ ID NO:50, or (vi) a light chain comprising the amino acid sequence of SEQ ID NO:51 and a heavy chain comprising the amino acid sequence of SEQ ID NO:52, or (vii) a light chain comprising the amino acid sequence of SEQ ID NO:53 and a heavy chain comprising the amino acid sequence of SEQ ID NO:54, or (viii) a light chain comprising the amino acid sequence of SEQ ID NO:55 and a heavy chain comprising the amino acid sequence of SEQ ID NO:56, or (ix) a light chain comprising the amino acid sequence of SEQ ID NO:57 and a heavy chain comprising the amino acid sequence of SEQ ID NO:58, or (x) a light chain comprising the amino acid sequence of SEQ ID NO:59 and a heavy chain comprising the amino acid sequence of SEQ ID NO:60, or (xi) a light chain comprising the amino acid sequence of SEQ ID NO:61 and a heavy chain comprising the amino acid sequence of SEQ ID NO:62, or (xii) a light chain comprising the amino acid sequence of SEQ ID NO:63 and a heavy chain comprising the amino acid sequence of SEQ ID NO:64, or (xiii) a light chain comprising the amino acid sequence of SEQ ID NO:65 and a heavy chain comprising the amino acid sequence of SEQ ID NO:66, or (xiv) a light chain comprising the amino acid sequence of SEQ ID NO:67 and a heavy chain comprising the amino acid sequence of SEQ ID NO:68, or (xv) a light chain comprising the amino acid sequence of SEQ ID NO:69 and a heavy chain comprising the amino acid sequence of SEQ ID NO:70, or (xvi) a light chain comprising the amino acid sequence of SEQ ID NO:71 and a heavy chain comprising the amino acid sequence of SEQ ID NO:72, or (xvii) a light chain comprising the amino acid sequence of SEQ ID NO:73 and a heavy chain comprising the amino acid sequence of SEQ ID NO:74, or (xviii) a light chain comprising the amino acid sequence of SEQ ID NO:75 and a heavy chain comprising the amino acid sequence of SEQ ID NO:76, or (xix) a light chain comprising the amino acid sequence of SEQ ID NO:77 and a heavy chain comprising the amino acid sequence of SEQ ID NO:78, or (xx) a light chain comprising the amino acid sequence of SEQ ID NO:79 and a heavy chain comprising the amino acid sequence of SEQ ID NO:80, or (xxi) a light chain comprising the amino acid sequence of SEQ ID NO:81 and a heavy chain comprising the amino acid sequence of SEQ ID NO:82, or (xxii) a light chain comprising the amino acid sequence of SEQ ID NO:83 and a heavy chain comprising the amino acid sequence of SEQ ID NO:84, or (xxiii) a light chain comprising the amino acid sequence of SEQ ID NO:85 and a heavy chain comprising the amino acid sequence of SEQ ID NO:86, or (xxiv) a light chain comprising the amino acid sequence of SEQ ID NO:87 and a heavy chain comprising the amino acid sequence of SEQ ID NO:88, or (xxv) a light chain comprising the amino acid sequence of SEQ ID NO:89 and a heavy chain comprising the amino acid sequence of SEQ ID NO:90, or (xxvi) a light chain comprising the amino acid sequence of SEQ ID NO:91 and a heavy chain comprising the amino acid sequence of SEQ ID NO:92, or (xxvii) a light chain comprising the amino acid sequence of SEQ ID NO:93 and a heavy chain comprising the amino acid sequence of SEQ ID NO:94, or (xxviii) a light chain comprising the amino acid sequence of SEQ ID NO:95 and a heavy chain comprising the amino acid sequence of SEQ ID NO:96, or (xxix) a light chain comprising the amino acid sequence of SEQ ID NO:97 and a heavy chain comprising the amino acid sequence of SEQ ID NO:98, or (xxx) a light chain comprising the amino acid sequence of SEQ ID NO:99 and a heavy chain comprising the amino acid sequence of SEQ ID NO:100, or (xxxi) a light chain comprising the amino acid sequence of SEQ ID NO:
- 101 and a heavy chain comprising the amino acid sequence of SEQ ID NO:102, or (xxxii) a light chain comprising the amino acid sequence of SEQ ID NO:103 and a heavy chain comprising the amino acid sequence of SEQ ID NO:104, or (xxxiii) a light chain comprising the amino acid sequence of SEQ ID NO:105 and a heavy chain comprising the amino acid sequence of SEQ ID NO:106, or (xxxiv) a light chain comprising the amino acid sequence of SEQ ID NO:107 and a heavy chain comprising the amino acid sequence of SEQ ID NO:108, or (xxxv) a light chain comprising the amino acid sequence of SEQ ID NO:109 and a heavy chain comprising the amino acid sequence of SEQ ID NO:110, or (xxxvi) a light chain comprising the amino acid sequence of SEQ ID NO:111 and a heavy chain comprising the amino acid sequence of SEQ ID NO:112, or (xxxvii) a light chain comprising the amino acid sequence of SEQ ID NO:113 and a heavy chain comprising the amino acid sequence of SEQ ID NO:114, or (xxxviii) a light chain comprising the amino acid sequence of SEQ ID NO:
- 115 and a heavy chain comprising the amino acid sequence of SEQ ID NO:116, or (xxxix) a light chain comprising the amino acid sequence of SEQ ID NO:
- 117 and a heavy chain comprising the amino acid sequence of SEQ ID NO:118, or (xl) a light chain comprising the amino acid sequence of SEQ ID NO:119 and a heavy chain comprising the amino acid sequence of SEQ ID NO:120, or (xli) a light chain comprising the amino acid sequence of SEQ ID NO:
- 121 and a heavy chain comprising the amino acid sequence of SEQ ID NO:122, or (xlii) a light chain comprising the amino acid sequence of SEQ ID NO:123 and a heavy chain comprising the amino acid sequence of SEQ ID NO:124, or (xliii) a light chain comprising the amino acid sequence of SEQ ID NO:125 and a heavy chain comprising the amino acid sequence of SEQ ID NO:126, or (xliv) a light chain comprising the amino acid sequence of SEQ ID NO:127 and a heavy chain comprising the amino acid sequence of SEQ ID NO:128, or (xlv) a light chain comprising the amino acid sequence of SEQ ID NO:129 and a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 130, or (xlvi) a light chain comprising the amino acid sequence of SEQ ID NO:131 and a heavy chain comprising the amino acid sequence of SEQ ID NO:132, or (xlvii) a light chain comprising the amino acid sequence of SEQ ID NO:133 and a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 134, or (xlviii) a light chain comprising the amino acid sequence of SEQ ID NO:135 and a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 136, or (xlix) a light chain comprising the amino acid sequence of SEQ ID NO:137 and a heavy chain comprising the amino acid sequence of SEQ ID NO:138, or (1) a light chain comprising the amino acid sequence of SEQ ID NO:139 and a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 140, or (li) a light chain comprising the amino acid sequence of SEQ ID NO:141 and a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 142, or (lii) a light chain comprising the amino acid sequence of SEQ ID NO:143 and a heavy chain comprising the amino acid sequence of SEQ ID NO:144.
A TrkB binding molecule comprising or consisting of two scFv's, wherein each scFv binds specifically to TrkB.
An scFv binding specifically to TrkB comprising (i) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:213 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:214, or (ii) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:215 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:216.
An antibody molecule binding specifically to VEGF comprising:
- (i) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:189, and
- a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:191;
- or
- a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:192;
- or
- a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:194;
- (ii) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:190, and
- a light chain variable domain comprising the amino acid sequence of SEQ ID NO:192;
- or
- a light chain variable domain comprising the amino acid sequence of SEQ ID NO:193.
-39. (canceled)
Dependencies are inferred from the claim text.