JPWO2020123664A5

JPWO2020123664A5 -

Info

Publication number: JPWO2020123664A5
Application number: JP2021533155A
Authority: JP
Publication date: 2022-12-15

Claims

それを必要とする対象において卵巣癌を処置するための医薬組成物であって、前記医薬組成物が、ＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２、およびＣＤＲ－Ｈ３を含む可変重鎖ドメイン（ＶＨ）配列、ならびにＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２、およびＣＤＲ－Ｌ３を含む可変軽鎖ドメイン（ＶＬ）配列を含む単離抗体を含み、
ａ．前記ＣＤＲ－Ｈ１が配列番号９または３９に記載の配列を含み、
ｂ．前記ＣＤＲ－Ｈ２が配列番号１０または４０に記載の配列を含み、
ｃ．前記ＣＤＲ－Ｈ３が配列番号１１または４１に記載の配列を含み、
ｄ．前記ＣＤＲ－Ｌ１が配列番号１２または４２に記載の配列を含み、
ｅ．前記ＣＤＲ－Ｌ２が配列番号１３または４３に記載の配列を含み、かつ
ｆ．前記ＣＤＲ－Ｌ３が配列番号１４または４４に記載の配列を含む
医薬組成物。 1. A pharmaceutical composition for treating ovarian cancer in a subject in need thereof, said pharmaceutical composition comprising a variable heavy chain domain (VH) sequence comprising CDR-H1, CDR-H2, and CDR-H3; and an isolated antibody comprising a variable light chain domain (VL) sequence comprising CDR-L1, CDR-L2, and CDR-L3 ;
a. said CDR-H1 comprises a sequence set forth in SEQ ID NO: 9 or 39;
b. said CDR-H2 comprises a sequence set forth in SEQ ID NO: 10 or 40;
c. said CDR-H3 comprises a sequence set forth in SEQ ID NO: 11 or 41;
d. said CDR-L1 comprises the sequence set forth in SEQ ID NO: 12 or 42;
e. said CDR-L2 comprises the sequence set forth in SEQ ID NO: 13 or 43, and
f. said CDR-L3 comprises the sequence set forth in SEQ ID NO: 14 or 44
pharmaceutical composition .

前記抗体が以下を含む、請求項１に記載の医薬組成物：2. The pharmaceutical composition of claim 1, wherein said antibody comprises:
ａ．配列番号３９に記載の配列を含むＣＤＲ－Ｈ１、a. a CDR-H1 comprising the sequence set forth in SEQ ID NO:39;
ｂ．配列番号４０に記載の配列を含むＣＤＲ－Ｈ２、b. a CDR-H2 comprising the sequence set forth in SEQ ID NO:40;
ｃ．配列番号４１に記載の配列を含むＣＤＲ－Ｈ３、c. a CDR-H3 comprising the sequence set forth in SEQ ID NO:41;
ｄ．配列番号４２に記載の配列を含むＣＤＲ－Ｌ１、d. a CDR-L1 comprising the sequence set forth in SEQ ID NO:42;
ｅ．配列番号４３に記載の配列を含むＣＤＲ－Ｌ２、及びe. CDR-L2 comprising the sequence set forth in SEQ ID NO: 43, and
ｆ．配列番号４４に記載の配列を含むＣＤＲ－Ｌ３。f. CDR-L3 comprising the sequence set forth in SEQ ID NO:44.

前記抗体が、配列番号１、３、または５に示されるＶＨ配列を含む、請求項１に記載の医薬組成物。 2. The pharmaceutical composition of Claim 1 , wherein said antibody comprises a VH sequence set forth in SEQ ID NO: 1, 3, or 5.

前記抗体が、配列番号１、３、または５に示されるＶＨ配列；及び配列番号２、４、または６に示されるＶＬ配列を含む、請求項１に記載の医薬組成物。 2. The pharmaceutical composition of claim 1 , wherein said antibody comprises a VH sequence as set forth in SEQ ID NO:1, 3 or 5; and a VL sequence as set forth in SEQ ID NO:2, 4 or 6.

前記抗体が、配列番号１に示されるＶＨ配列を含む、請求項１に記載の医薬組成物。 2. The pharmaceutical composition of claim 1 , wherein said antibody comprises the VH sequence shown in SEQ ID NO:1.

前記抗体が、配列番号２に示されるＶＬ配列を含む、請求項１に記載の医薬組成物。2. The pharmaceutical composition of claim 1, wherein said antibody comprises the VL sequence shown in SEQ ID NO:2.

前記抗体が、配列番号１に示されるＶＨ配列及び配列番号２に示されるＶＬ配列を含む、請求項１に記載の医薬組成物。 2. The pharmaceutical composition of claim 1 , wherein said antibody comprises the VH sequence set forth in SEQ ID NO:1 and the VL sequence set forth in SEQ ID NO:2.

前記抗体が、配列番号２５に示される重鎖配列及び配列番号２６に示される軽鎖配列を含む、請求項１に記載の医薬組成物。 2. The pharmaceutical composition of claim 1 , wherein said antibody comprises the heavy chain sequence set forth in SEQ ID NO:25 and the light chain sequence set forth in SEQ ID NO:26.

前記抗体が、表面プラズモン共鳴（ＳＰＲ）アッセイで測定された、約１、２、３、４、５、または５．１２×１０^－９Ｍ以下のＫ_ＤでヒトＴＲＥＭ２に結合する、請求項１に記載の医薬組成物。 The antibody is about 1, 2, 3, 4, 5, or 5 . 2. The pharmaceutical composition of claim 1 , which binds to human _TREM2 with a KD of 12 x ^10-9 M or less.

前記抗体が、ＴＲＥＭ２＋骨髄細胞、任意で、非刺激性骨髄細胞、任意で、腫瘍内骨髄細胞を、特異的に殺傷、枯渇、または無効化することが可能である、請求項１に記載の医薬組成物。 2. A medicament according to claim 1 , wherein said antibody is capable of specifically killing, depleting or neutralizing TREM2+ myeloid cells, optionally non-stimulated myeloid cells, optionally intratumoral myeloid cells. composition .

前記抗体が、抗体依存性細胞媒介性細胞傷害（ＡＤＣＣ）活性、抗体媒介性細胞貪食（ＡＤＣＰ）活性、または補体依存性細胞傷害（ＣＤＣ）活性を有する、請求項１に記載の医薬組成物。 2. The pharmaceutical composition of claim 1 , wherein said antibody has antibody-dependent cell-mediated cytotoxicity (ADCC) activity , antibody-mediated cytophagocytosis (ADCP) activity, or complement-dependent cytotoxicity (CDC) activity. things .

前記抗体が、モノクローナル抗体である、請求項１に記載の医薬組成物。 2. The pharmaceutical composition of claim 1 , wherein said antibody is a monoclonal antibody.

前記抗体が、アフコシル化されている、請求項１に記載の医薬組成物。 2. The pharmaceutical composition of claim 1 , wherein said antibody is afucosylated.

前記抗体が、ヒトＩｇＧ１の重鎖定常領域を含む、請求項１に記載の医薬組成物。 2. The pharmaceutical composition of claim 1 , wherein said antibody comprises a human IgGl heavy chain constant region.

前記対象が、免疫療法を以前に受けているか、同時に受けるか、またはその後に受けることになる、請求項１に記載の医薬組成物。 2. The pharmaceutical composition of claim 1 , wherein the subject has previously received, concurrently received, or will receive immunotherapy.

前記免疫療法が、チェックポイント阻害薬；Ｔ細胞のチェックポイント阻害薬；抗ＰＤ１抗体；抗ＰＤＬ１抗体；抗ＣＴＬＡ４抗体；養子Ｔ細胞療法；ＣＡＲ－Ｔ細胞療法；樹状細胞ワクチン；単球ワクチン；Ｔ細胞及び抗原提示細胞の両方に結合する抗原結合タンパク質；ＢｉＴＥ二重抗原結合タンパク質；トール様受容体リガンド；サイトカイン；細胞傷害療法；化学療法；放射線療法；小分子阻害薬；小分子アゴニスト；免疫調節薬；ならびにエピジェネティック調節薬のうちの少なくとも１つである、請求項１５に記載の医薬組成物。 T cell checkpoint inhibitor; anti-PD1 antibody; anti-PDL1 antibody; anti-CTLA4 antibody; adoptive T cell therapy; CAR-T cell therapy; BiTE dual antigen binding proteins; toll-like receptor ligands; cytokines; cytotoxic therapies; chemotherapy; radiotherapy; small molecule inhibitors; 16. The pharmaceutical composition of claim 15 , which is at least one of: a modulatory agent; and an epigenetic modulatory agent.

前記免疫療法が、抗ＰＤ１抗体、抗ＰＤＬ１抗体、または抗ＣＴＬＡ４抗体からなる群から選択される、請求項１６に記載の医薬組成物。 17. The pharmaceutical composition of claim 16 , wherein said immunotherapy is selected from the group consisting of anti-PDl antibodies, anti-PDLl antibodies, or anti-CTLA4 antibodies.

それを必要とする対象において胃癌を処置するための医薬組成物であって、前記医薬組成物が、ＣＤＲ－Ｈ１、ＣＤＲ－Ｈ２、およびＣＤＲ－Ｈ３を含む可変重鎖ドメイン（ＶＨ）配列、ならびにＣＤＲ－Ｌ１、ＣＤＲ－Ｌ２、およびＣＤＲ－Ｌ３を含む可変軽鎖ドメイン（ＶＬ）配列を含む単離抗体を含み、
ａ．前記ＣＤＲ－Ｈ１が配列番号９または３９に記載の配列を含み、
ｂ．前記ＣＤＲ－Ｈ２が配列番号１０または４０に記載の配列を含み、
ｃ．前記ＣＤＲ－Ｈ３が配列番号１１または４１に記載の配列を含み、
ｄ．前記ＣＤＲ－Ｌ１が配列番号１２または４２に記載の配列を含み、
ｅ．前記ＣＤＲ－Ｌ２が配列番号１３または４３に記載の配列を含み、かつ
ｆ．前記ＣＤＲ－Ｌ３が配列番号１４または４４に記載の配列を含む
医薬組成物。 A pharmaceutical composition for treating gastric cancer in a subject in need thereof, said pharmaceutical composition comprising a variable heavy chain domain (VH) sequence comprising CDR-H1, CDR-H2, and CDR-H3; an isolated antibody comprising a variable light domain (VL) sequence comprising CDR-L1, CDR-L2, and CDR-L3 ;
a. said CDR-H1 comprises a sequence set forth in SEQ ID NO: 9 or 39;
b. said CDR-H2 comprises a sequence set forth in SEQ ID NO: 10 or 40;
c. said CDR-H3 comprises a sequence set forth in SEQ ID NO: 11 or 41;
d. said CDR-L1 comprises the sequence set forth in SEQ ID NO: 12 or 42;
e. said CDR-L2 comprises the sequence set forth in SEQ ID NO: 13 or 43, and
f. said CDR-L3 comprises the sequence set forth in SEQ ID NO: 14 or 44
pharmaceutical composition .

対象由来の試料中のＴＲＥＭ２タンパク質の発現レベルを決定する方法であって、前記試料と抗ＴＲＥＭ２抗体とを接触させる工程、および免疫組織化学アッセイを実施する工程を含む、方法。A method of determining the expression level of TREM2 protein in a sample from a subject, comprising contacting said sample with an anti-TREM2 antibody, and performing an immunohistochemical assay.

前記抗体が、ＰＩＴ２Ｄを含む、請求項１９に記載の方法。20. The method of claim 19, wherein said antibody comprises PIT2D.