Invented by John Dixon Gray, Heyue Zhou, Sorrento Therapeutics Inc

The market for antibody therapeutics that bind CD137 is experiencing significant growth and is poised to revolutionize the field of immunotherapy. CD137, also known as 4-1BB, is a co-stimulatory molecule found on the surface of immune cells, including T cells and natural killer (NK) cells. Binding of antibodies to CD137 enhances the activation and proliferation of these immune cells, leading to a more robust and targeted immune response against cancer cells. The use of CD137-targeting antibodies in cancer treatment has gained considerable attention in recent years due to their potential to overcome the limitations of traditional therapies. Unlike chemotherapy or radiation, which often have systemic toxicities and limited efficacy, CD137 antibodies offer a more targeted approach by specifically activating immune cells to attack cancer cells. One of the key advantages of CD137-targeting antibodies is their ability to induce long-lasting immune memory. When CD137 is engaged, T cells and NK cells undergo a process called clonal expansion, resulting in the generation of a large population of activated immune cells. These cells not only eliminate the existing tumor but also persist in the body, providing long-term protection against cancer recurrence. This durable immune response is a major breakthrough in cancer treatment and has the potential to transform the way we approach cancer therapy. The market for antibody therapeutics that bind CD137 is expected to witness substantial growth in the coming years. According to a report by Grand View Research, the global cancer immunotherapy market is projected to reach $126.9 billion by 2026, with CD137-targeting antibodies playing a significant role in this growth. The increasing prevalence of cancer and the growing demand for more effective and targeted treatments are driving the adoption of CD137 antibodies in the market. Several pharmaceutical companies are actively developing CD137-targeting antibodies and conducting clinical trials to evaluate their safety and efficacy. For example, Bristol Myers Squibb’s urelumab and Merck’s utomilumab are two CD137-targeting antibodies currently in clinical development. These antibodies have shown promising results in early-phase clinical trials, demonstrating their potential as a novel class of immunotherapies. However, the market for CD137-targeting antibodies is not without challenges. One of the main concerns is the potential for immune-related adverse events (irAEs) due to the potent activation of the immune system. These irAEs can range from mild to severe and require close monitoring and management. Additionally, the high cost of antibody therapeutics remains a barrier to widespread adoption, limiting access for patients. Despite these challenges, the market for antibody therapeutics that bind CD137 holds immense potential for improving cancer treatment outcomes. The ability to harness the power of the immune system to fight cancer has already revolutionized the field of oncology, and CD137-targeting antibodies are poised to further advance this progress. As more clinical data becomes available and regulatory approvals are obtained, the market for CD137 antibodies is expected to grow exponentially, offering new hope for cancer patients worldwide.

The Sorrento Therapeutics Inc invention works as follows

Compositions and methods related to or derived by anti-CD137 antibody are disclosed. There are also disclosed CD137 antibody fragments, derivatives, and polypeptides that contain these fragments. There are also nucleic acid encoding these antibodies, polypeptides and antibody fragments as well as cells containing such polynucleotides. Methods of producing such antibodies and polypeptides have been disclosed, along with methods for making them. The diseases that are treatable include cancers, autoimmune disorders and viral infections.

Background for Antibody Therapeutics that Bind CD137

CD137 belongs to the TNF receptor family. Other names for this receptor include tumor necrosis-factor receptor superfamily 9 (TNFRSF9) and induced by Lymphocyte Activation (ILA). CD137 is expressed by activated cells of T lymphocytes, although to a greater extent on CD8 T cells than CD4 T. CD137 is also expressed on dendritic and follicular cells, natural killers, granulocytes, and blood vessel wall cells at inflammation sites. CD137’s costimulatory action on activated T-cells is one of its most notable activities. Crosslinking CD137 increases T cell proliferation, IL-2 production and cytolytic activities. It can also enhance immune activity in mice to eliminate tumors.

CD137 is an T-cell costimulatory induced receptor (Nam et.al., Curr. Cancer Drug Targets, 5:357-363 (2005); Watts et al., Annu. Rev. Immunol., 23:23-68 (2005)). CD137 is expressed not only on CD4+ and CD8+ activated T cells but also on CD4+CD25+ regulatory cells, natural killer cells (NK) and the NK-T cell, as well as on monocytes and neutrophils. Its natural ligand, CD137L, has been described on antigen-presenting cells including B cells, monocyte/macrophages, and dendritic cells (Watts et al., Annu. Rev. Immunol., 23:23-68 (2005)). CD137 interacts with its ligand to increase TCR-induced T cell proliferation, cytokine release, functional maturation and prolong CD8+ T-cell life (Nam et.al., Curr. Cancer Drug Targets, 5:357-363 (2005), Watts et al., Annu. Rev. Immunol., 23:23-68 (2005)).

The authors conclude that “signaling through CD137, either by CD137L or agonistic mAbs against CD137, leads to increased TCR induced T cell proliferation and maturation as well as prolonged CD8+ T cells survival.” These effects result from: (1) the activation of the NF-?B, c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK), and p38 mitogen-activated protein kinase (MAPK) signaling pathways, and (2) the control of anti-apoptotic and cell cycle-related gene expression. “Experiments in CD137-deficient mice and CD137L deficient mice also demonstrated the importance CD137 costimulation for the generation of fully competent T cells.

IL-2- and IL-15-activated NK cells express CD137. Ligation of CD137 with agonistic mAbs promotes NK cell proliferation and IFN? “IL-2 and IL-15 activated NK cells express CD137, and ligation of CD137 by agonistic mAbs stimulates NK cell proliferation and IFN-? In vitro, CD137-stimulated NK cell proliferation is also promoted by CD137-stimulated NK. According to their costimulatory role, agonist mAbs for CD137 have shown to promote rejection and eradication of established tumors. They also broaden antiviral CD8+T cell responses and increase the cytolytic capacity of T cells. These studies support that CD137 signaling may promote T cell function, which could enhance immunity against infections and tumors.

Other anti-CD137 antibodies were disclosed in U.S. Patent No. No. No. 7,288,638; U.S. Pat. No. No. 6,887.673 [4E9] or BMS-554271; U.S. Nos. Nos. No. No. 6,974,863; U.S. Pat. No. No. U.S. Pat. describes additional CD137-agonistic antibodies. Nos. Nos.

The present disclosure provides fully human antibodies against CD137 to overcome these and other deficiencies of the previous antibodies.

The present disclosure discloses a fully-human anti-CD137 IgG antibody that binds a CD137 epitope at a binding affinity at least 10?6M. This antibody has a heavy chains variable domain sequence which is at least 95 % identical to, at most 96% identical to, at most 97% identical to, at the least 98% identical to, or at the least 99% identical to, the amino acid sequences chosen from the group including SEQ ID No. 1, SEQ NO. SEQ NO. 5, SEQ NO. 6, SEQ NO. SEQ ID No. SEQ ID No. 11, SEQ NO. SEQ ID No. SEQ ID No. 16, SEQ ID No. 19 SEQ ID No. 21 SEQ ID No. 23 SEQ ID No. 25 SEQ ID No. 27 SEQ ID No. SEQ NO. 31 SEQ ID No. SEQ ID No. 33 35 SEQ ID No. 37 SEQ ID No. 39 SEQ ID No. 41, SEQ NO. 43 SEQ ID No. 45 SEQ ID No. 47 SEQ ID No. 49, SEQ NO. 51, SEQ NO. 53 SEQ ID No. 55, SEQ NO. 57, SEQ NO. 59, SEQ NO. 61, SEQ NO. 63, SEQ NO. 65, SEQ NO. SEQ ID No. 69, SEQ NO. 71, SEQ NO. 73, SEQ NO. 75, SEQ NO. SEQ ID No. 79, SEQ NO. 81, SEQ NO. 83, SEQ NO. 85, SEQ NO. 87, SEQ NO. 89, SEQ NO. 91, SEQ NO. 93, SEQ NO. 95, SEQ NO. 97, SEQ NO. 99, SEQ NO. 101, SEQ NO. SEQ ID No. 105, SEQ NO. 107, SEQ NO. 109, SEQ NO. 111, SEQ NO. 113, SEQ NO. 115, SEQ NO. 117, SEQID NO. 119, SEQ NO. 121, SEQ NO. 123, SEQ NO. 125, SEQ NO. 127, SEQ NO. 129, SEQ NO. 130, SEQ NO. 131, SEQ NO. 132, SEQ NO. 133, SEQ NO. 134, SEQ NO. 135, SEQID NO. 136, SEQ NO. 137, SEQ NO. 138, SEQ NO. 139, SEQ NO. 140, SEQ NO. 141, SEQ NO. 142, SEQ NO. SEQ ID No. 2, SEQ NO. SEQ NO. 6, SEQ NO. SEQ ID No. SEQ ID No. SEQ ID No. SEQ NO. 16, SEQ NO. 16, SEQ ID No. SEQ NO. 22 SEQ ID No. 22, SEQ ID No. SEQ ID No. 28 SEQ ID No. SEQ NO. SEQ ID No. 32 34, SEQ NO. 36, SEQ NO. 38 SEQ ID No. 40, SEQ NO. 42, SEQ NO. 44, SEQ NO. 46, SEQ NO. 48 SEQ ID No. 50 SEQ ID No. 52, SEQ NO. SEQ ID No. 54 SEQ ID No. 58, SEQ NO. 60, SEQ NO. 62, SEQ NO. 64, SEQ NO. 66, SEQ NO. 68, SEQ NO. 70, SEQ NO. 72, SEQ NO. SEQ ID No. 76, SEQ NO. 78, SEQ NO. 80, SEQ NO. 82, SEQ NO. 84, SEQ NO. 86, SEQ NO. 88, SEQ NO. 90, SEQ NO. 92, SEQ NO. 94, SEQ NO. 96, SEQ NO. 98, SEQ NO. 100, SEQ NO. 102, SEQ NO. 104, SEQ NO. 106, SEQ NO. 108, SEQ NO. 110, SEQ NO. 112, SEQ NO. 114, SEQ NO. 116, SEQ NO. 118, SEQ NO. 120, SEQ NO. SEQ ID No. 124, SEQ NO. SEQ ID No. Combinations thereof, 128, heavy chain/light chain variable domain sequences. In one embodiment the fully human antibodies has both a heavier chain and lighter chain, where the antibody has an heavy chain/lighter chain variable domain selected from a group consisting SEQ ID No. 1/SEQ NO. 2 (called A1 herein), SEQ ID NO. 3/SEQ NO. 4 (called A4 herein), SEQ ID NO. 5/SEQ NO. 6 (called A11 herein), SEQ ID NO. 7/SEQ NO. 8 (called B1 herein), SEQ ID NO. 9/SEQ NO. 10 (called B3 herein), SEQ ID NO. 11/SEQ NO. 12 (called B12 herein), SEQ ID NO. 13/SEQ NO. 14 (called C2 herein), SEQ ID NO. 15/SEQ NO. 16 (called C3 herein), SEQ ID NO. 17/SEQ NO. 18 (called C7 herein), SEQ ID NO. 19/SEQ NO. 20 (called C11 herein), SEQ ID NO. 21/SEQ NO. 22 (called C12 herein), SEQ ID NO. 23/SEQ NO. 24 (called D1 herein), SEQ ID NO. 25/SEQ NO. 26 (called D4 herein), SEQ ID NO. 27/SEQ NO. 28 (called D6 herein), SEQ ID NO. 29/SEQ NO. 30 (called D7 herein), SEQ ID NO. 31/SEQ NO. 32 (called D8 herein), SEQ ID NO. 33/SEQ NO. 34 (called D10 herein), SEQ ID NO. 35/SEQ NO. 36 (called E2 herein), SEQ ID NO. 37/SEQ NO. 38 (called E5 herein), SEQ ID NO. 39/SEQ NO. 40 (called E7 herein), SEQ ID NO. 41/SEQ NO. 42 (called F5 herein), SEQ ID NO. 43/SEQ NO. 44 (called F7 herein), SEQ ID NO. 45/SEQ NO. 46 (called F11 herein), SEQ ID NO. 47/SEQ NO. 48 (called G1 herein), SEQ ID NO. 49/SEQ NO. 50 (called G2 herein), SEQ ID NO. 51/SEQ NO. 52 (called G3 herein), SEQ ID NO. 53/SEQ NO. 54 (called G5 herein), SEQ ID NO. 55/SEQ NO. 56 (called G6 herein), SEQ ID NO. 57/SEQ NO. 58 (called G8 herein), SEQ ID NO. 59/SEQ NO. 60 (called G12 herein), SEQ ID NO. 61/SEQ NO. 62 (called H4 herein), SEQ ID NO. 63/SEQ NO. 64 (called H7 herein), SEQ ID NO. 65/SEQ NO. 66 (called H8 herein), SEQ ID NO. 67/SEQ NO. 68 (called H10 herein), SEQ ID NO. 69/SEQ NO. 70 (called H11 herein), SEQ ID NO. 71/SEQ NO. 72 (called C3sh1A1 herein), SEQ ID NO. 73/SEQ NO. 74 (called C3sh1A2 herein), SEQ ID NO. 75/SEQ NO. 76 (called C3sh1A5 herein), SEQ ID NO. 77/SEQ NO. 78 (called C3sh1A9 herein), SEQ ID NO. 79/SEQ NO. 80 (called C3sh1B2 herein), SEQ ID NO. 81/SEQ NO. 82 (called C3sh1B4 herein), SEQ ID NO. 83/SEQ NO. 84 (called C3sh1B6 herein), SEQ ID NO. SEQ ID No. 86 (called C3sh1B9 herein), SEQ ID NO. 87/SEQ NO. 88 (called C3sh1C1 herein), SEQ ID NO. 89/SEQ NO. 90 (called C3sh1C2 herein), SEQ ID NO. 91/SEQ NO. 92 (called C3sh1C7 herein), SEQ ID NO. 93/SEQ NO. 94 (called C3sh1D1 herein), SEQ ID NO. 95/SEQ NO. 96 (called C3sh1D4 herein), SEQ ID NO. 97/SEQ NO. 98 (called C3sh1D6 herein), SEQ ID NO. 99/SEQ NO. 100 (called C3sh1E2 herein), SEQ ID NO. 101/SEQ NO. 102 (called C3sh1E7 herein), SEQ ID NO. 103/SEQ NO. 104 (called C3sh1E9 herein), SEQ ID NO. 105/SEQ NO. 106 (called C3sh1F1 herein), SEQ ID NO. 107/SEQ NO. 108 (called C3sh1F10 herein), SEQ ID NO. 109/SEQ NO. 110 (called C3sh1F12 herein), SEQ ID NO. 111/SEQ NO. 112 (called C3sh1F2 herein), SEQ ID NO. 113/SEQ NO. 114 (called C3sh1G1 herein), SEQ ID NO. 115/SEQ NO. 116 (called C3sh1G11 herein), SEQ ID NO. 117/SEQ NO. 118 (called C3sh1G2 herein), SEQ ID NO. 119/SEQ NO. 120 (called C3sh1G3 herein), SEQ ID NO. 121/SEQ NO. 122 (called C3sh1G5 herein), SEQ ID NO. 123/SEQ NO. 124 (called C3sh1G8 herein), SEQ ID NO. 125/SEQ NO. 126 (called C3sh1H10 herein), SEQ ID NO. 127/SEQ NO. 128 (called C3sh1H4 herein), SEQ ID NO. 129/SEQ NO. 28 (called MA8 herein), SEQ ID NO. 130/SEQ NO. 28 (called MB1 herein), SEQ ID NO. 131/SEQ NO. 28 (called MB3 herein), SEQ ID NO. 132/SEQ NO. 28 (called MB10 herein), SEQ ID NO. 133/SEQ NO. 28 (called MB12 herein), SEQ ID NO. 134/SEQ NO. 28 (called MC8 herein), SEQ ID NO. 135/SEQ NO. 28 (called MD1 herein), SEQ ID NO. 136/SEQ NO. 28 (called MD4 herein), SEQ ID NO. 137/SEQ NO. 28 (called MSA11 herein), SEQ ID NO. 138/SEQ NO. 28 (called MSB7 herein), SEQ ID NO. 139/SEQ NO. 28 (called MSD2 herein), SEQ ID NO. 140/SEQ NO. 28 (called MSE3 herein), SEQ ID NO. 141/SEQ NO. 28 (called MSE5 herein), SEQ ID NO. 142/SEQ NO. 28 (called MSC8 herein), SEQ ID NO. SEQ ID No. 28 (called MSH1 in this document), and combinations thereof.

In one embodiment of the invention, it includes an isolated antigen-binding anti-CD137 antibodies, or an antigen binding fragment thereof. The antigen-binding antigens are comprised of a heavy-chain variable domain containing complementarity-determining regions (CDRs), as specified in the heavy-chain variable

The present disclosure discloses a Fab anti-CD137 fully human antibody fragment with a variable region of a heavy and a light chains, the heavy chain having a sequence that is 95%, 96%, 97%, 98%, or 99% identical to the amino acids sequences chosen from the group consisting SEQ ID No. 1, SEQ NO. SEQ NO. 5, SEQ NO. SEQ NO. SEQ ID No. SEQ ID No. SEQ ID No. SEQ ID No. SEQ NO. 16, SEQ ID No. 19 SEQ ID No. 21 SEQ ID No. 23 SEQ ID No. 25 SEQ ID No. 27 SEQ ID No. 29, SEQ NO. 31 SEQ ID No. SEQ ID No. 33 35 SEQ ID No. 37 SEQ ID No. 39 SEQ ID No. 41, SEQ NO. 43 SEQ ID No. 45 SEQ ID No. 47 SEQ ID No. 49, SEQ NO. 51, SEQ NO. 53 SEQ ID No. 55, SEQ NO. 57, SEQ NO. 59, SEQ NO. 61, SEQ NO. 63, SEQ NO. 65, SEQ NO. 67, SEQ NO. 69, SEQ NO. 71, SEQ NO. 73, SEQ NO. 75, SEQ NO. 77, SEQ NO. 79, SEQ NO. 81, SEQ NO. 83, SEQ NO. 85, SEQ NO. 87, SEQ NO. 89, SEQ NO. 91, SEQ NO. 93, SEQ NO. 95, SEQ NO. 97, SEQ NO. 99, SEQ NO. 101, SEQ NO. SEQ ID No. 105, SEQ NO. 107, SEQ NO. 109, SEQ NO. 111, SEQ NO. 113, SEQ NO. 115, SEQ NO. 117, SEQID NO. 119, SEQ NO. 121, SEQ NO. 123, SEQ NO. 125, SEQ NO. 127, SEQ NO. 129, SEQ NO. 130, SEQ NO. SEQ ID No. 131 132, SEQ NO. 133, SEQ NO. 134, SEQ NO. 135, SEQID NO. 136, SEQ NO. 137, SEQ NO. 138, SEQ NO. 139, SEQ NO. SEQ ID No. 141, SEQ NO. 142, SEQ NO. 143 and combinations thereof and having a light-chain variable domain sequence which is at least 95 % identical to the amino acid series consisting of SEQID NO. 2, SEQ NO. SEQ NO. SEQ ID No. 8, SEQ NO. SEQ ID No. SEQ ID No. SEQ NO. SEQ NO. 16, SEQ ID No. SEQ NO. 22 SEQ ID No. 22, SEQ ID No. 26, SEQ NO. 28 SEQ ID No. 30, SEQ NO. SEQ ID No. 32 34, SEQ NO. 36, SEQ NO. 38 SEQ ID No. 40, SEQ NO. 42, SEQ NO. 44, SEQ NO. 46, SEQ NO. 48 SEQ ID No. SEQ ID No. 50 52, SEQ NO. SEQ ID No. 54 SEQ ID No. 58, SEQ NO. 60, SEQ NO. 62, SEQ NO. 64, SEQ NO. SEQ ID No. 66 68, SEQ NO. 70, SEQ NO. 72, SEQ NO. 74, SEQ NO. 76, SEQ NO. 78, SEQ NO. 80, SEQ NO. 82, SEQ NO. 84, SEQ NO. 86, SEQ NO. 88, SEQ NO. 90, SEQ NO. 92, SEQ NO. 94, SEQ NO. 96, SEQ NO. 98, SEQ NO. 100, SEQ NO. 102, SEQ NO. 104, SEQ NO. 106, SEQ NO. 108, SEQ NO. SEQ ID No. 112, SEQ NO. 114, SEQ NO. 116, SEQ NO. 118, SEQ NO. 120, SEQ NO. 122, SEQ NO. 124, SEQ NO. 126. SEQ ID No. “128, and combinations thereof.

In one embodiment the fully human antigen Fab fragment includes both a heavy-chain variable domain and a lighter-chain variable domain, wherein the antibody contains a heavy-chain/lightchain variable domain sequence that is selected from a group consisting of SEQ ID No. 1/SEQ NO. 2, SEQ NO. 3/SEQ NO. 4, SEQ NO. 5, SEQ ID No. 6, SEQ NO. 7, SEQ ID No. 8, SEQ NO. 9, SEQ ID No. 10, SEQ NO. 11, SEQ ID No. 12 SEQ ID No. 13/SEQ NO. 14 SEQ ID No. 15/SEQ NO. 16 SEQ ID No. 17, SEQ ID No. 18 SEQ ID No. 19/SEQ NO. 20 SEQ ID No. 21/SEQ NO. 22 SEQ ID No. 23/SEQ NO. 24 SEQ ID No. 25/SEQ NO. 26 SEQ ID No. 27/SEQ NO. 28 SEQ ID No. 29/SEQ NO. 30 SEQ ID No. 31/SEQ NO. 32 SEQ ID No. 32, SEQ ID No. 34 SEQ ID No. 35/SEQ NO. 36 SEQ ID No. 37/SEQ NO. 38 SEQ ID No. 39/SEQ NO. 40 SEQ ID No. 41/SEQ NO. 42, SEQ NO. 43/SEQ NO. SEQ ID No. 44 45/SEQ NO. 46, SEQ NO. 47/SEQ NO. 48 SEQ ID No. 49/SEQ NO. 50 SEQ ID No. 51/SEQ NO. 52, SEQ NO. 53/SEQ NO. 54, SEQ NO. 55/SEQ NO. 56, SEQ NO. 57/SEQ NO. 58, SEQ NO. 59/SEQ NO. 60, SEQ NO. 61/SEQ NO. 62, SEQ NO. 63/SEQ NO. 64, SEQ NO. 65/SEQ NO. 66/SEQ ID No. 67/SEQ NO. 68, SEQ NO. 69/SEQ NO. SEQ ID No. 71/SEQ NO. 72, SEQ NO. 73/SEQ NO. 74, SEQ NO. 75/SEQ NO. 76/SEQ ID No. 77/SEQ NO. 78, SEQ NO. 79/SEQ NO. 80, SEQ NO. 81/SEQ NO. 82, SEQ NO. 83/SEQ NO. 84, SEQ NO. 85/SEQ NO. 86 SEQ ID No. 87/SEQ NO. 88, SEQ NO. 89/SEQ NO. 90, SEQ NO. 91/SEQ NO. 92, SEQ NO. 93/SEQ NO. 94, SEQ NO. 95/SEQ NO. 96, SEQ NO. 97/SEQ NO. 98, SEQ NO. 99/SEQ NO. SEQ ID No. 100 101/SEQ NO. SEQ ID No. 102 103/SEQID NO. 104 SEQ ID No. 105/SEQ NO. 106, SEQ NO. 107/SEQ NO. 108, SEQ NO. 109/SEQ NO. 110, SEQ NO. SEQ ID NO. 112, SEQ NO. 113/SEQ NO. SEQ ID No. 114 115/SEQ NO. 116, SEQ NO. 117/SEQID NO. 118, SEQID NO. 119/SEQID NO. 120, SEQID NO. 121/SEQ NO. 122 SEQ ID No. 123/SEQID NO. 124 SEQ ID No. 125/SEQ NO. 126, SEQ NO. 127/SEQ NO. 128, SEQ NO. 129/SEQ NO. 28, SEQ NO. 129/SEQ NO. 28 SEQ ID No. 13, SEQ ID No. 28 SEQ ID No. 13, SEQ ID No. 28 SEQ ID No. 133/SEQ NO. 28 SEQ ID No. 28, SEQ ID No. 28 SEQ ID No. 135/SEQ NO. 28 SEQ ID No. 136/SEQ NO. 28, SEQ NO. 28, SEQ ID No. 28, SEQ NO. 138/SEQ NO. SEQ ID No. 139/SEQ NO. SEQ ID No. 140/SEQ NO. 28 SEQ ID No. 14, SEQ ID No. 28 SEQ ID No. 142/SEQ NO. 28 and SEQ ID No. SEQ ID No. 28.

The present disclosure discloses an anti-CD137 human single chain antibody with a variable region of a heavy and light chains, and a peptide linking the heavy and light chains variable domain regions. In this case, the heavy chain’s variable region is at least 95 percent identical to amino acid sequences chosen from the group consisting SEQ ID No. 1. SEQ ID No. 3, SEQ NO. SEQ NO. SEQ NO. 7, SEQ NO. SEQ ID No. SEQ ID No. 13, SEQ NO. SEQ ID No. 16, SEQ ID No. 19 SEQ ID No. 21 SEQ ID No. 23 SEQ ID No. 25 SEQ ID No. 27 SEQ ID No. SEQ NO. 31 SEQ ID No. SEQ ID No. 33 35 SEQ ID No. 37 SEQ ID No. 39 SEQ ID No. 41, SEQ NO. SEQ ID No. 43 45 SEQ ID No. 47 SEQ ID No. 49, SEQ NO. 51, SEQ NO. 53 SEQ ID No. 55, SEQ NO. 57, SEQ NO. 59, SEQ NO. 61, SEQ NO. 63, SEQ NO. 65, SEQ NO. SEQ ID No. 69, SEQ NO. 71, SEQ NO. 73, SEQ NO. 75, SEQ NO. 77, SEQ NO. 79, SEQ NO. 81, SEQ NO. 83, SEQ NO. 85, SEQ NO. 87, SEQ NO. 89, SEQ NO. 91, SEQ NO. 93, SEQ NO. 95, SEQ NO. 97, SEQ NO. 99, SEQ NO. 101, SEQ NO. 103, SEQ NO. 105, SEQ NO. 107, SEQ NO. 109, SEQ NO. 111, SEQ NO. 113, SEQ NO. 115, SEQ NO. 117, SEQID NO. 119, SEQ NO. 121, SEQ NO. 123, SEQ NO. 125, SEQ NO. 127, SEQ NO. 129, SEQ NO. 130, SEQ NO. 131, SEQ NO. 132, SEQ NO. 133, SEQ NO. 134, SEQ NO. 135, SEQID NO. 136, SEQ NO. 137, SEQ NO. 138, SEQ NO. 139, SEQ NO. SEQ ID No. 141, SEQ NO. 142, SEQ NO. SEQ ID No. SEQ ID No. SEQ NO. SEQ ID No. SEQ ID No. SEQ ID No. SEQ ID No. SEQ NO. SEQ NO. 16, SEQ ID No. 20, SEQ NO. 22 SEQ ID No. 22, SEQ ID No. SEQ ID No. 28 SEQ ID No. SEQ NO. 32, SEQ NO. SEQ ID No. 34 36, SEQ NO. 38 SEQ ID No. 40, SEQ NO. 42, SEQ NO. SEQ ID No. 44 46, SEQ NO. 48 SEQ ID No. 50 SEQ ID No. 52, SEQ NO. SEQ ID No. 54 56, SEQ NO. 58, SEQ NO. 60, SEQ NO. 62, SEQ NO. 64, SEQ NO. SEQ ID No. 66 68, SEQ NO. 70, SEQ NO. 72, SEQ NO. 74, SEQ NO. 76, SEQ NO. 78, SEQ NO. SEQ ID No. 82, SEQ NO. 84, SEQ NO. 86, SEQ NO. 88, SEQ NO. 90, SEQ NO. 92, SEQ NO. 94, SEQ NO. 96, SEQ NO. 98, SEQ NO. 100, SEQ NO. SEQ ID No. 104, SEQ NO. 106, SEQ NO. 108, SEQ NO. 110, SEQ NO. 112, SEQ NO. 114, SEQ NO. 116, SEQ NO. 118, SEQ NO. 120, SEQ NO. 122, SEQ NO. 124, SEQ NO. SEQ ID No. “128, and combinations thereof.

In certain embodiments the fully human single-chain antibody has both a region of heavy chain variable and a region of light chain variable, wherein the fully human single-chain antibody has a sequence for the heavy chain/light domain that is selected from a group consisting SEQ ID No. 1/SEQ NO. SEQ ID No. 3/SEQ NO. 4, SEQ NO. 5, SEQ ID No. SEQ NO. 7, SEQ ID No. 8, SEQ NO. 9, SEQ ID No. SEQ ID No. 11, SEQ ID No. 12 SEQ ID No. 13/SEQ NO. 14 SEQ ID No. 15/SEQ NO. 16 SEQ ID No. 17, SEQ ID No. 18 SEQ ID No. 19/SEQ NO. 20 SEQ ID No. 21/SEQ NO. 22 SEQ ID No. 23/SEQ NO. 24 SEQ ID No. 25/SEQ NO. 26 SEQ ID No. 27/SEQ NO. 28 SEQ ID No. 29/SEQ NO. 30 SEQ ID No. 31/SEQ NO. 32 SEQ ID No. 32, SEQ ID No. 34 SEQ ID No. 35/SEQ NO. 36 SEQ ID No. 37/SEQ NO. 38 SEQ ID No. 39/SEQ NO. 40 SEQ ID No. 41/SEQ NO. 42, SEQ NO. 43/SEQ NO. 44 SEQ ID No. 45/SEQ NO. 46, SEQ NO. 47/SEQ NO. 48 SEQ ID No. 49/SEQ NO. 50 SEQ ID No. 51/SEQ NO. 52, SEQ NO. 53/SEQ NO. 54, SEQ NO. 55/SEQ NO. SEQ ID No. 57/SEQ NO. 58, SEQ NO. 59/SEQ NO. 60, SEQ NO. 61/SEQ NO. 62, SEQ NO. 63/SEQ NO. 64, SEQ NO. 65/SEQ NO. SEQ ID No. 66 67/SEQ NO. 68, SEQ NO. 69/SEQ NO. SEQ ID No. 71/SEQ NO. 72, SEQ NO. 73/SEQ NO. SEQ ID No. 75/SEQ NO. 76/SEQ ID No. 77/SEQ NO. 78, SEQ NO. 79/SEQ NO. 80, SEQ NO. 81/SEQ NO. 82, SEQ NO. 83/SEQ NO. 84, SEQ NO. 85/SEQ NO. 86 SEQ ID No. 87/SEQ NO. 88, SEQ NO. 89/SEQ NO. 90, SEQ NO. 91/SEQ NO. 92, SEQ NO. 93/SEQ NO. 94, SEQ NO. 95/SEQ NO. 96, SEQ NO. 97/SEQ NO. 98, SEQ NO. 99/SEQ NO. 100 SEQ ID No. 101/SEQ NO. 102, SEQ NO. 103/SEQID NO. 104 SEQ ID No. 105/SEQ NO. 106, SEQ NO. 107/SEQ NO. 108, SEQ NO. 109/SEQ NO. 110, SEQ NO. SEQ ID NO. 112, SEQ NO. 112/SEQ ID No. SEQ ID No. 114 115/SEQ NO. 116, SEQ NO. 117/SEQID NO. 118, SEQID NO. 119/SEQID NO. 120, SEQID NO. 121/SEQ NO. 122 SEQ ID No. 123/SEQID NO. SEQ ID No. 124 125/SEQ NO. 126, SEQ NO. 127/SEQ NO. 128, SEQ NO. 129/SEQ NO. 28, SEQ NO. SEQ ID No. 28 SEQ ID No. 13, SEQ ID No. 28 SEQ ID No. 13, SEQ ID No. 28 SEQ ID No. 133/SEQ NO. 28 SEQ ID No. 28, SEQ ID No. 28 SEQ ID No. 135/SEQ NO. 28 SEQ ID No. 136/SEQ NO. 28, SEQ NO. 28, SEQ ID No. SEQ ID No. 138/SEQ NO. SEQ ID No. 139/SEQ NO. 28, SEQ ID No. 140/SEQ NO. 28 SEQ ID No. 14, SEQ ID No. 28 SEQ ID No. 14, SEQ ID No. 28 SEQ ID No. SEQ ID No. 143/28 28 and combinations thereof.

The present disclosure also provides a method to treat a disease that requires either stimulation or suppression of immune responses, which includes administering an anti CD137 polypeptide. This fully human antibody contains a heavy-chain variable domain sequence at least 95 percent identical or 96% identical or 97% identical or 98% identical or 99% identical with the amino acid sequences chosen from the group of SEQID NO. “The present disclosure further provides a method for treating a disease requiring either stimulation of immune responses or suppression, comprising administering an anti-CD137 polypeptide. The fully human antibody has a heavy chain variable domain sequence that is at least 95% identical, at least 96% identical, at least 97% identical,at most 99% identical to the amino acid sequences selected from the group consisting of SEQ ID No. 3, SEQ NO. SEQ NO. 6, SEQ NO. SEQ ID No. SEQ ID No. 11, SEQ NO. SEQ ID No. SEQ NO. 16, SEQ ID No. 19 SEQ ID No. 21 SEQ ID No. 23 SEQ ID No. 25 SEQ ID No. 27 SEQ ID No. SEQ NO. 31 SEQ ID No. SEQ ID No. 33 35 SEQ ID No. 37 SEQ ID No. 39 SEQ ID No. 41, SEQ NO. 43 SEQ ID No. 45 SEQ ID No. 47 SEQ ID No. 49, SEQ NO. 51, SEQ NO. 53 SEQ ID No. 55, SEQ NO. 57, SEQ NO. 59, SEQ NO. 61, SEQ NO. 63, SEQ NO. SEQ ID No. 65 67, SEQ NO. 69, SEQ NO. 71, SEQ NO. 73, SEQ NO. 75, SEQ NO. 77, SEQ NO. 79, SEQ NO. 81, SEQ NO. 83, SEQ NO. SEQ ID No. 87, SEQ NO. 89, SEQ NO. 91, SEQ NO. 93, SEQ NO. 95, SEQ NO. 97, SEQ NO. 99, SEQ NO. 101, SEQ NO. SEQ ID No. 105, SEQ NO. 107, SEQ NO. 109, SEQ NO. 111, SEQ NO. 113, SEQ NO. 115, SEQ NO. 117, SEQID NO. 119, SEQ NO. 121, SEQ NO. 123, SEQ NO. 125, SEQ NO. 127, SEQ NO. 129, SEQ NO. 130, SEQ NO. 131, SEQ NO. 132, SEQ NO. 133, SEQ NO. 134, SEQ NO. 135, SEQID NO. 136, SEQ NO. 137, SEQ NO. 138, SEQ NO. 139, SEQ NO. 140, SEQ NO. 141, SEQ NO. 142, SEQ NO. 143 and combinations thereof and having a light-chain variable domain sequence at least 95% the same as that of an amino acid consisting SEQ ID No. 2, SEQ NO. SEQ NO. SEQ ID No. SEQ ID No. SEQ ID No. SEQ ID No. SEQ NO. 16, SEQ NO. 16, SEQ ID No. SEQ NO. 22 SEQ ID No. 22, SEQ ID No. 26, SEQ NO. 28 SEQ ID No. SEQ NO. SEQ ID No. 32 34, SEQ NO. 36, SEQ NO. 38 SEQ ID No. SEQ ID No. 40 42, SEQ NO. 44, SEQ NO. 46, SEQ NO. 48 SEQ ID No. 50 SEQ ID No. 52, SEQ NO. 54, SEQ NO. 56, SEQ NO. 58, SEQ NO. 60, SEQ NO. 62, SEQ NO. 64, SEQ NO. 66, SEQ NO. 68, SEQ NO. 70, SEQ NO. 72, SEQ NO. 74, SEQ NO. 76, SEQ NO. 78, SEQ NO. 80, SEQ NO. 82, SEQ NO. 84, SEQ NO. 86, SEQ NO. 88, SEQ NO. 90, SEQ NO. SEQ ID No. 94, SEQ NO. 96, SEQ NO. 98, SEQ NO. 100, SEQ NO. SEQ ID No. 104, SEQ NO. 106, SEQ NO. 108, SEQ NO. 110, SEQ NO. 112, SEQ NO. 114, SEQ NO. 116, SEQ NO. 118, SEQ NO. 120, SEQ NO. SEQ ID No. 124, SEQ NO. 126, SEQID NO. SEQ ID No. 1, SEQ NO. SEQ NO. SEQ NO. SEQ NO. SEQ ID No. SEQ ID No. SEQ ID No. SEQ ID No. SEQ NO. 16, SEQ ID No. 19 SEQ ID No. 21 SEQ ID No. 23 SEQ ID No. 25 SEQ ID No. 27 SEQ ID No. SEQ NO. 31 SEQ ID No. SEQ ID No. 33 35 SEQ ID No. 37 SEQ ID No. 39 SEQ ID No. 41, SEQ NO. SEQ ID No. 43 45 SEQ ID No. 47 SEQ ID No. 49, SEQ NO. 51, SEQ NO. 53 SEQ ID No. 55, SEQ NO. 57, SEQ NO. 59, SEQ NO. 61, SEQ NO. 63, SEQ NO. 65, SEQ NO. 67, SEQ NO. 69, SEQ NO. 71, SEQ NO. 73, SEQ NO. 75, SEQ NO. 77, SEQ NO. 79, SEQ NO. 81, SEQ NO. 83, SEQ NO. SEQ ID No. 87, SEQ NO. 89, SEQ NO. 91, SEQ NO. 93, SEQ NO. 95, SEQ NO. 97, SEQ NO. 99, SEQ NO. 101, SEQ NO. 103, SEQ NO. 105, SEQ NO. 107, SEQ NO. 109, SEQ NO. 111, SEQ NO. 113, SEQ NO. 115, SEQ NO. 117, SEQID NO. 119, SEQ NO. 121, SEQ NO. 123, SEQ NO. 125, SEQ NO. 127, SEQ NO. 129, SEQ NO. 130, SEQ NO. 131, SEQ NO. 132, SEQ NO. 133, SEQ NO. 134, SEQ NO. 135, SEQID NO. 136, SEQ NO. 137, SEQ NO. 138, SEQ NO. 139, SEQ NO. 140, SEQ NO. 141, SEQ NO. 142, SEQ NO. SEQ ID No. SEQ ID No. SEQ NO. SEQ ID No. SEQ ID No. SEQ ID No. SEQ ID No. SEQ NO. SEQ NO. 16, SEQ ID No. 20, SEQ NO. 22 SEQ ID No. 22, SEQ ID No. SEQ ID No. 28 SEQ ID No. 30, SEQ NO. SEQ ID No. 32 SEQ ID No. 34 36, SEQ NO. 38 SEQ ID No. SEQ ID No. 40 SEQ ID No. 42 SEQ ID No. 44 46, SEQ NO. 48 SEQ ID No. SEQ ID No. 50 52, SEQ NO. 54, SEQ NO. 56, SEQ NO. 58, SEQ NO. 60, SEQ NO. 62, SEQ NO. 64, SEQ NO. SEQ ID No. 66 68, SEQ NO. 70, SEQ NO. 72, SEQ NO. SEQ ID No. 76, SEQ NO. 78, SEQ NO. 80, SEQ NO. 82, SEQ NO. 84, SEQ NO. 86, SEQ NO. 88, SEQ NO. 90, SEQ NO. 92, SEQ NO. 94, SEQ NO. 96, SEQ NO. 98, SEQ NO. 100, SEQ NO. 102, SEQ NO. 104, SEQ NO. 106, SEQ NO. 108, SEQ NO. SEQ ID No. 112, SEQ NO. SEQ ID No. 116, SEQ NO. 118, SEQ NO. 120, SEQ NO. 122, SEQ NO. 124, SEQ NO. 126, SEQID NO. The single chain human antibodies have the heavy chain variable sequences that are at least 95%, 96%, 97%, 98%, or 99% identical to the amino acids sequences selected in the group consisting SEQ ID No. 1, SEQ NO. SEQ NO. SEQ NO. SEQ NO. 7, SEQ NO. SEQ ID No. SEQ ID No. 13, SEQ NO. SEQ NO. 16, SEQ ID No. 19 SEQ ID No. 21 SEQ ID No. 23 SEQ ID No. 25 SEQ ID No. 27 SEQ ID No. SEQ NO. 31 SEQ ID No. SEQ ID No. 33 35 SEQ ID No. 37 SEQ ID No. 39 SEQ ID No. 41, SEQ NO. 43 SEQ ID No. 45 SEQ ID No. 47 SEQ ID No. 49, SEQ NO. 51, SEQ NO. 53 SEQ ID No. 55, SEQ NO. 57, SEQ NO. 59, SEQ NO. 61, SEQ NO. 63, SEQ NO. 65, SEQ NO. 67, SEQ NO. 69, SEQ NO. 71, SEQ NO. 73, SEQ NO. 75, SEQ NO. SEQ ID No. 79, SEQ NO. 81, SEQ NO. 83, SEQ NO. 85, SEQ NO. 87, SEQ NO. 89, SEQ NO. 91, SEQ NO. 93, SEQ NO. 95, SEQ NO. 97, SEQ NO. 99, SEQ NO. 101, SEQ NO. SEQ ID No. 105, SEQ NO. 107, SEQ NO. 109, SEQ NO. 111, SEQ NO. 113, SEQ NO. 115, SEQ NO. 117, SEQID NO. 119, SEQ NO. 121, SEQ NO. 123, SEQ NO. 125, SEQ NO. 127, SEQ NO. 129, SEQ NO. 130, SEQ NO. 131, SEQ NO. 132, SEQ NO. 133, SEQ NO. 134, SEQ NO. 135, SEQID NO. SEQ ID No. 136 137, SEQ NO. 138, SEQ NO. 139, SEQ NO. 140, SEQ NO. 141, SEQ NO. 142, SEQ NO. 143 and combinations thereof. The light chain variable sequence must be at least 95 percent identical to the amino acids sequence consisting SEQ ID No. SEQ ID No. SEQ NO. 6, SEQ NO. 8, SEQ NO. SEQ ID No. SEQ ID No. SEQ NO. SEQ NO. 16, SEQ ID No. SEQ NO. 22 SEQ ID No. 22, SEQ ID No. SEQ ID No. 28 SEQ ID No. 30, SEQ NO. 32, SEQ NO. 34, SEQ NO. 36, SEQ NO. 38 SEQ ID No. 40, SEQ NO. 42, SEQ NO. 44, SEQ NO. 46, SEQ NO. 48 SEQ ID No. 50 SEQ ID No. 52, SEQ NO. 54, SEQ NO. 56, SEQ NO. 58, SEQ NO. 60, SEQ NO. 62, SEQ NO. 64, SEQ NO. SEQ ID No. 66 68, SEQ NO. 70, SEQ NO. 72, SEQ NO. 74, SEQ NO. 76, SEQ NO. 78, SEQ NO. 80, SEQ NO. 82, SEQ NO. 84, SEQ NO. 86, SEQ NO. 88, SEQ NO. 90, SEQ NO. 92, SEQ NO. 94, SEQ NO. 96, SEQ NO. 98, SEQ NO. 100, SEQ NO. 102, SEQ NO. 104, SEQ NO. 106, SEQ NO. 108, SEQ NO. 110, SEQ NO. 112, SEQ NO. SEQ ID No. 116, SEQ NO. SEQ ID No. 120, SEQ NO. 122, SEQ NO. 124, SEQ NO. 126. SEQ ID No. “128, and combinations thereof.

In one embodiment the fully human antibodies has both a heavier chain and a lighter chain, wherein the antibody contains a heavy-chain/light-chain variable domain sequence that is selected from a group consisting SEQ ID No. 1/SEQ NO. 2 (called A1 herein), SEQ ID NO. 3/SEQ NO. 4 (called A4 herein), SEQ ID NO. 5/SEQ NO. 6 (called A11 herein), SEQ ID NO. 7/SEQ NO. 8 (called B1 herein), SEQ ID NO. 9/SEQ NO. 10 (called B3 herein), SEQ ID NO. 11/SEQ NO. 12 (called B12 herein), SEQ ID NO. 13/SEQ NO. 14 (called C2 herein), SEQ ID NO. 15/SEQ NO. 16 (called C3 herein), SEQ ID NO. 17/SEQ NO. 18 (called C7 herein), SEQ ID NO. 19/SEQ NO. 20 (called C11 herein), SEQ ID NO. 21/SEQ NO. 22 (called C12 herein), SEQ ID NO. 23/SEQ NO. 24 (called D1 herein), SEQ ID NO. 25/SEQ NO. 26 (called D4 herein), SEQ ID NO. 27/SEQ NO. 28 (called D6 herein), SEQ ID NO. 29/SEQ NO. 30 (called D7 herein), SEQ ID NO. 31/SEQ NO. 32 (called D8 herein), SEQ ID NO. 33/SEQ NO. 34 (called D10 herein), SEQ ID NO. 35/SEQ NO. 36 (called E2 herein), SEQ ID NO. 37/SEQ NO. 38 (called E5 herein), SEQ ID NO. 39/SEQ NO. 40 (called E7 herein), SEQ ID NO. 41/SEQ NO. 42 (called F5 herein), SEQ ID NO. 43/SEQ NO. 44 (called F7 herein), SEQ ID NO. 45/SEQ NO. 46 (called F11 herein), SEQ ID NO. 47/SEQ NO. 48 (called G1 herein), SEQ ID NO. 49/SEQ NO. 50 (called G2 herein), SEQ ID NO. 51/SEQ NO. 52 (called G3 herein), SEQ ID NO. 53/SEQ NO. 54 (called G5 herein), SEQ ID NO. 55/SEQ NO. 56 (called G6 herein), SEQ ID NO. 57/SEQ NO. 58 (called G8 herein), SEQ ID NO. 59/SEQ NO. 60 (called G12 herein), SEQ ID NO. 61/SEQ NO. 62 (called H4 herein), SEQ ID NO. 63/SEQ NO. 64 (called H7 herein), SEQ ID NO. 65/SEQ NO. 66 (called H8 herein), SEQ ID NO. 67/SEQ NO. 68 (called H10 herein), SEQ ID NO. 69/SEQ NO. 70 (called H11 herein), SEQ ID NO. 71/SEQ NO. 72 (called C3sh1A1 herein), SEQ ID NO. 73/SEQ NO. 74 (called C3sh1A2 herein), SEQ ID NO. 75/SEQ NO. 76 (called C3sh1A5 herein), SEQ ID NO. 77/SEQ NO. 78 (called C3sh1A9 herein), SEQ ID NO. 79/SEQ NO. 80 (called C3sh1B2 herein), SEQ ID NO. 81/SEQ NO. 82 (called C3sh1B4 herein), SEQ ID NO. 83/SEQ NO. 84 (called C3sh1B6 herein), SEQ ID NO. SEQ ID No. 86 (called C3sh1B9 herein), SEQ ID NO. 87/SEQ NO. 88 (called C3sh1C1 herein), SEQ ID NO. 89/SEQ NO. 90 (called C3sh1C2 herein), SEQ ID NO. 91/SEQ NO. 92 (called C3sh1C7 herein), SEQ ID NO. 93/SEQ NO. 94 (called C3sh1D1 herein), SEQ ID NO. 95/SEQ NO. 96 (called C3sh1D4 herein), SEQ ID NO. 97/SEQ NO. 98 (called C3sh1D6 herein), SEQ ID NO. 99/SEQ NO. 100 (called C3sh1E2 herein), SEQ ID NO. 101/SEQ NO. 102 (called C3sh1E7 herein), SEQ ID NO. 103/SEQ NO. 104 (called C3sh1E9 herein), SEQ ID NO. 105/SEQ NO. 106 (called C3sh1F1 herein), SEQ ID NO. 107/SEQ NO. 108 (called C3sh1F10 herein), SEQ ID NO. 109/SEQ NO. 110 (called C3sh1F12 herein), SEQ ID NO. 111/SEQ NO. 112 (called C3sh1F2 herein), SEQ ID NO. 113/SEQ NO. 114 (called C3sh1G1 herein), SEQ ID NO. 115/SEQ NO. 116 (called C3sh1G11 herein), SEQ ID NO. 117/SEQ NO. 118 (called C3sh1G2 herein), SEQ ID NO. 119/SEQ NO. 120 (called C3sh1G3 herein), SEQ ID NO. 121/SEQ NO. 122 (called C3sh1G5 herein), SEQ ID NO. 123/SEQ NO. 124 (called C3sh1G8 herein), SEQ ID NO. 125/SEQ NO. 126 (called C3sh1H10 herein), SEQ ID NO. 127/SEQ NO. 128 (called C3sh1H4 herein), SEQ ID NO. 129/SEQ NO. 28 (called MA8 herein), SEQ ID NO. 130/SEQ NO. 28 (called MB1 herein), SEQ ID NO. 131/SEQ NO. 28 (called MB3 herein), SEQ ID NO. 132/SEQ NO. 28 (called MB10 herein), SEQ ID NO. 133/SEQ NO. 28 (called MB12 herein), SEQ ID NO. 134/SEQ NO. 28 (called MC8 herein), SEQ ID NO. 135/SEQ NO. 28 (called MD1 herein), SEQ ID NO. 136/SEQ NO. 28 (called MD4 herein), SEQ ID NO. 137/SEQ NO. 28 (called MSA11 herein), SEQ ID NO. 138/SEQ NO. 28 (called MSB7 herein), SEQ ID NO. 139/SEQ NO. 28 (called MSD2 herein), SEQ ID NO. 140/SEQ NO. 28 (called MSE3 herein), SEQ ID NO. 141/SEQ NO. 28 (called MSE5 herein), SEQ ID NO. 142/SEQ NO. 28 (called MSC8 herein), SEQ ID NO. SEQ ID No. 28 (called MSH1 in this document), and combinations thereof. Preferably, a fully human single-chain antibody will have both a heavy-chain variable domain and a lighter-chain variable domain, with the heavy chain/light-chain variable domain selected from a group consisting SEQ ID No. 1/SEQ NO. 2, SEQ NO. 3/SEQ NO. SEQ ID No. 5, SEQ ID No. SEQ NO. 7, SEQ ID No. 8, SEQ NO. 9, SEQ ID No. SEQ ID No. 11, SEQ ID No. 12 SEQ ID No. 13/SEQ NO. 14 SEQ ID No. 15/SEQ NO. 16 SEQ ID No. 17, SEQ ID No. 18 SEQ ID No. 19/SEQ NO. 20 SEQ ID No. 21/SEQ NO. 22 SEQ ID No. 23/SEQ NO. 24 SEQ ID No. 25/SEQ NO. 26 SEQ ID No. 27/SEQ NO. 28 SEQ ID No. 29/SEQ NO. 30 SEQ ID No. 31/SEQ NO. 32 SEQ ID No. 32, SEQ ID No. SEQ ID No. 34 35/SEQ NO. 36 SEQ ID No. 37/SEQ NO. 38 SEQ ID No. 39/SEQ NO. 40 SEQ ID No. 41/SEQ NO. 42 and combinations thereof

Preferred, the disease should be selected from the group of cancers and autoimmune diseases, or viral infections.

In certain embodiments the anti-CD137 antibodies is IgG1 in isotype. In some embodiments, anti-CD137 antibodies are IgG4 isotypes.

In certain embodiments the anti-CD137 antibodies, or antigen binding fragments, described herein are recombinant.

The invention also provides pharmaceutical compositions containing an effective amount or anti-CD137 fragments or antibodies disclosed herein and a pharmaceutically accepted carrier.

The invention, in certain embodiments, features a method for treating cancer on a human being in need of it. This involves administering to the patient an effective amount (or antigen-binding fraction thereof) of the anti-CD137 antigen, so that the cancer is treated. Cancers that can be treated include ovarian, colorectal, melanoma and renal cancers, as well as hepatocellular cancer, breast, head and neck, lung and liver cancers.

DESCRIPTION DU DRAWINGS

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