Radiolabeled anti-LAG3 antibodies for immuno-PET imaging
Radiolabeled anti-LAG3 antibodies and their use in immuno-PET imaging are provided herein. Included are methods of detecting the presence of LAG3 proteins in a patient or sample.
1. A compound of Formula (III):
wherein A is an antibody or antigen-binding fragment thereof that binds LAG3 and k is from 1-30, and
wherein the antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (HCDRs) in a heavy chain variable region (HCVR), wherein the HCVR has an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 18, 34, 50, 66, 82, 98, 130, 146, 162, 178, 194, 210, 226, 242, 258, 274, 290, 322, 338, 354, 370, 386, 402, 418, 434, 458, 466, 474, 482, 490, 498, 506, 514, 538, and 554; and three light chain complementarity determining regions (LCDRs) in a light chain variable region (LCVR), wherein the LCVR has an amino acid sequence selected from the group consisting of SEQ ID NOs: 10, 26, 42, 58, 74, 90, 106, 122, 138, 154, 170, 186, 202, 218, 234, 250, 266, 282, 298, 314, 330, 346, 362, 378, 394, 410, 426, 442, 522, 530, 546, and 562.
2. The compound of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (HCDRs) and three light chain complementarity determining regions (LCDRs) within the heavy chain variable region (HCVR)/light chain variable region (LCVR) sequence pair selected from the group consisting of SEQ ID NOs: 2/10, 18/26, 34/42, 50/58, 66/74, 82/90, 98/106, 130/138, 146/154, 162/170, 178/186, 194/202, 210/218, 226/234, 242/250, 258/266, 274/282, 290/298, 322/330, 338/346, 354/362, 370/378, 386/394, 402/410, 418/426, 434/442, 458/522, 466/522, 474/522, 482/522, 490/522, 498/530, 506/530, 514/530, 538/546, and 554/562.
3. The compound of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises three HCDRs and three LCDRs selected from the group consisting of SEQ ID NOs: 4/6/8/12/14/16, 20/22/24/28/30/32, 36/38/40/44/46/48, 52/54/56/60/62/64, 68/70/72/76/78/80, 84/86/88/92/94/96, 100/102/104/108/110/112, 132/134/136/140/142/144, 148/150/152/156/158/160, 164/166/168/172/174/176, 180/182/184/188/190/192, 196/198/200/204/206/208, 212/214/216/220/222/224, 228/230/232/236/238/240, 244/246/248/252/254/256, 260/262/264/268/270/272, 276/278/280/284/286/288, 292/294/296/300/302/304, 324/326/328/332/334/336, 340/342/344/348/350/352, 356/358/360/364/366/368, 372/374/376/380/382/384, 388/390/392/396/398/400, 404/406/408/412/414/416, 420/422/424/428/430/432, 436/438/440/444/446/448, 460/462/464/524/526/528, 468/470/472/524/526/528, 476/478/480/524/526/528, 484/486/488/524/526/528, 492/494/496/524/526/528, 500/502/504/532/534/536, 508/510/512/532/534/536, 516/518/520/532/534/536, 540/542/544/548/550/552, and 556/558/560/564/566/568.
4. The compound of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises three HCDRs in a HCVR of SEQ ID NO: 418; and three LCDRs in a LCVR of SEQ ID NO: 426.
5. The compound of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region (HCDR)-1 comprising SEQ ID No: 420; an HCDR2 comprising SEQ ID NO: 422; and an HCDR3 comprising SEQ ID NO: 424; a light chain complementarity determining region (LCDR)-1 comprising SEQ ID NO: 428; an LCDR2 comprising SEQ ID NO: 430; and an LCDR3 comprising SEQ ID NO: 432.
6. The compound of claim 1 , wherein k is greater than or equal to 1 but less than or equal to 2.
7. The compound of claim 1 , wherein k is 1 or 2.