JPWO2020014419A5 - - Google Patents

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JPWO2020014419A5
JPWO2020014419A5 JP2021500868A JP2021500868A JPWO2020014419A5 JP WO2020014419 A5 JPWO2020014419 A5 JP WO2020014419A5 JP 2021500868 A JP2021500868 A JP 2021500868A JP 2021500868 A JP2021500868 A JP 2021500868A JP WO2020014419 A5 JPWO2020014419 A5 JP WO2020014419A5
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domain
igg1
monomer
polypeptide
domain monomer
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JP2021500868A
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JP2021530989A (en
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Priority claimed from PCT/US2019/041306 external-priority patent/WO2020014419A2/en
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Claims (13)

ＰＤ－Ｌ１結合ドメインと、リンカーによって第２のＦｃドメインに結合された第１のＦｃドメインと、を含むＦｃ抗原結合ドメイン構築体であって、前記第１のＦｃドメインおよび前記第２のＦｃドメインが各々、ヘテロ二量体化選択性モジュールまたはホモ二量体化選択性モジュールのいずれかを含む、Ｆｃ抗原結合ドメイン構築体。 An Fc antigen-binding domain construct comprising a PD-L1 binding domain and a first Fc domain bound to a second Fc domain by a linker, wherein the first Fc domain and the second Fc domain Fc antigen-binding domain constructs, each comprising either a heterodimerization selectivity module or a homodimerization selectivity module. ＰＤ－Ｌ１結合ドメインと、
リンカーと、
ヒンジドメイン、ＣＨ２ドメイン、およびＣＨ３ドメインを含む第１のＩｇＧ１ Ｆｃドメイン単量体と、
第２のリンカーと、
ヒンジドメイン、ＣＨ２ドメイン、およびＣＨ３ドメインを含む第２のＩｇＧ１ Ｆｃドメイン単量体と、
任意選択の第３のリンカーと、
ヒンジドメイン、ＣＨ２ドメイン、およびＣＨ３ドメインを含む任意選択の第３のＩｇＧ１ Ｆｃドメイン単量体と、
を含むポリペプチドであって、
少なくとも２つのＦｃドメイン単量体が、ヘテロ二量体化選択性モジュールまたはホモ二量体化選択性モジュールのいずれかを含む、ポリペプチド。 PD-L1 binding domain and
With the linker
A first IgG1 Fc domain monomer comprising a hinge domain, a CH2 domain, and a CH3 domain, and
With the second linker
A second IgG1 Fc domain monomer comprising a hinge domain, a CH2 domain, and a CH3 domain, and
With an optional third linker,
With an optional third IgG1 Fc domain monomer comprising a hinge domain, a CH2 domain, and a CH3 domain,
It is a polypeptide containing
A polypeptide in which at least two Fc domain monomers contain either a heterodimerization selectivity module or a homodimerization selectivity module. 前記ＰＤ－Ｌ１結合ドメインが、抗体重鎖可変ドメインを含む、請求項２に記載のポリペプチド。 The polypeptide according to claim 2, wherein the PD-L1 binding domain comprises an antibody heavy chain variable domain. 前記ＰＤ－Ｌ１結合ドメインが、抗体軽鎖可変ドメインを含む、請求項２に記載のポリペプチド。 The polypeptide according to claim 2, wherein the PD-L1 binding domain comprises an antibody light chain variable domain. 前記第１のＩｇＧ１ Ｆｃドメイン単量体が、２つまたは４つの逆電荷変異を含み、前記第２のＩｇＧ１ Ｆｃドメイン単量体が、改変された突起を形成する変異を含む、請求項２に記載のポリペプチド。 2. The first IgG1 Fc domain monomer comprises two or four reverse charge mutations and the second IgG1 Fc domain monomer comprises a mutation that forms a modified process. The polypeptide described. 前記第１のＩｇＧ１ Ｆｃドメイン単量体が、改変された突起を形成する変異を含み、前記第２のＩｇＧ１ Ｆｃドメイン単量体が、２つまたは４つの逆電荷変異を含む、請求項２に記載のポリペプチド。 2. The first IgG1 Fc domain monomer comprises a mutation that forms a modified protrusion, and the second IgG1 Fc domain monomer comprises two or four reverse charge mutations. The polypeptide described. 前記第１のＩｇＧ１ Ｆｃドメイン単量体および第２のＩｇＧ定常ドメイン単量体の両方が、改変された突起を形成する変異を含む、請求項２に記載のポリペプチド。 The polypeptide of claim 2, wherein both the first IgG1 Fc domain monomer and the second IgG constant domain monomer contain mutations that form modified protrusions. 第３のリンカーと、第３のＩｇＧ１ Ｆｃドメイン単量体と、を含み、前記第１のＩｇＧ１ Ｆｃドメイン単量体、前記第２のＩｇＧ１ Ｆｃドメイン単量体、および前記第３のＩｇＧ１ Ｆｃドメイン単量体が各々、改変された突起を形成する変異を含む、請求項２に記載のポリペプチド。 It comprises a third linker and a third IgG1 Fc domain monomer, said first IgG1 Fc domain monomer, said second IgG1 Fc domain monomer, and said third IgG1 Fc domain. The polypeptide of claim 2, wherein each monomer comprises a mutation that forms a modified protrusion. 第３のリンカーと、第３のＩｇＧ１ Ｆｃドメイン単量体と、を含み、前記第１のＩｇＧ１ Ｆｃドメイン単量体および前記第２のＩｇＧ１ Ｆｃドメイン単量体の両方が各々、改変された突起を形成する変異を含み、前記第３のＩｇＧ１ Ｆｃドメイン単量体が、２つまたは４つの逆電荷変異を含む、請求項２に記載のポリペプチド。 A protrusion containing a third linker and a third IgG1 Fc domain monomer, each of which is a modified form of both the first IgG1 Fc domain monomer and the second IgG1 Fc domain monomer. The polypeptide of claim 2, wherein the third IgG1 Fc domain monomer comprises two or four reverse charge mutations. 第３のリンカーと、第３のＩｇＧ１ Ｆｃドメイン単量体と、を含み、前記第１のＩｇＧ１ Ｆｃドメイン単量体および前記第３のＩｇＧ１ Ｆｃドメイン単量体の両方が各々、改変された突起を形成する変異を含み、前記第２のＩｇＧ１ドメイン単量体が、２つまたは４つの逆電荷変異を含む、請求項２に記載のポリペプチド。 A protrusion containing a third linker and a third IgG1 Fc domain monomer, each of which is a modified form of both the first IgG1 Fc domain monomer and the third IgG1 Fc domain monomer. The polypeptide of claim 2, wherein the second IgG1 domain monomer comprises two or four reverse charge mutations. 第３のリンカーと、第３のＩｇＧ１ Ｆｃドメイン単量体と、を含み、前記第２のＩｇＧ１ Ｆｃドメイン単量体および前記第３のＩｇＧ１ Ｆｃドメイン単量体の両方が各々、改変された突起を形成する変異を含み、前記第１のＩｇＧ１ドメイン単量体が、２つまたは４つの逆電荷変異を含む、請求項２に記載のポリペプチド。 A protrusion containing a third linker and a third IgG1 Fc domain monomer, each of which is a modified form of both the second IgG1 Fc domain monomer and the third IgG1 Fc domain monomer. The polypeptide of claim 2, wherein the first IgG1 domain monomer comprises two or four reverse charge mutations. Ｆｃ抗原結合ドメイン構築体であって、
ａ）第１のポリペプチドであって、
ｉ）第１のＦｃドメイン単量体、
ｉｉ）第２のＦｃドメイン単量体、および
ｉｉｉ）前記第１のＦｃドメイン単量体と前記第２のＦｃドメイン単量体を結合する
リンカー
を含む、第１のポリペプチドと、
ｂ）第３のＦｃドメイン単量体を含む第２のポリペプチドと、
ｃ）第４のＦｃドメイン単量体を含む第３のポリペプチドと、
ｄ）前記第１のポリペプチド、前記第２のポリペプチド、または前記第３のポリペプチドに結合された抗原結合ドメインと
を含み、
前記第１のＦｃドメイン単量体と前記第３のＦｃドメイン単量体が組み合わさって第１のＦｃドメインを形成し、前記第２のＦｃドメイン単量体と前記第４のＦｃドメイン単量体が組み合わさって第２のＦｃドメインを形成し、前記Ｆｃ抗原結合ドメイン構築体が、単一Ｆｃドメインおよび前記ＰＤ－Ｌ１結合ドメインを有する構築体によって呈されない生物学的活性を含む、Ｆｃ抗原結合ドメイン構築体。 Fc antigen-binding domain construct
a) The first polypeptide,
i) First Fc domain monomer,
ii) a second Fc domain monomer, and ii) a first polypeptide comprising a linker that binds the first Fc domain monomer to the second Fc domain monomer.
b) With a second polypeptide containing a third Fc domain monomer,
c) With a third polypeptide containing a fourth Fc domain monomer,
d) Containing the first polypeptide, the second polypeptide, or an antigen binding domain bound to the third polypeptide.
The first Fc domain monomer and the third Fc domain monomer are combined to form a first Fc domain, and the second Fc domain monomer and the fourth Fc domain single amount are formed. Fc antigens that combine the bodies to form a second Fc domain, wherein the Fc antigen binding domain construct comprises a biological activity that is not exhibited by a single Fc domain and a construct having the PD-L1 binding domain. Combined domain construct. Ｆｃ抗原結合ドメイン構築体であって、
ａ）第１のポリペプチドであって、
ｉ）第１のＦｃドメイン単量体、
ｉｉ）第２のＦｃドメイン単量体、および
ｉｉｉ）前記第１のＦｃドメイン単量体と前記第２のＦｃドメイン単量体を結合するスペーサー
を含む、第１のポリペプチドと、
ｂ）第３のＦｃドメイン単量体を含む第２のポリペプチドと、
ｃ）第４のＦｃドメイン単量体を含む第３のポリペプチドと、
ｄ）前記第１のポリペプチド、前記第２のポリペプチド、または前記第３のポリペプチドに結合された抗原結合ドメインと
を含み、
前記第１のＦｃドメイン単量体と前記第３のＦｃドメイン単量体が組み合わさって第１のＦｃドメインを形成し、前記第２のＦｃドメイン単量体と前記第４のＦｃドメイン単量体が組み合わさって第２のＦｃドメインを形成する、Ｆｃ抗原結合ドメイン構築体。
Fc antigen-binding domain construct
a) The first polypeptide,
i) First Fc domain monomer,
ii) A second Fc domain monomer, and ii) A first polypeptide comprising a spacer that binds the first Fc domain monomer to the second Fc domain monomer.
b) With a second polypeptide containing a third Fc domain monomer,
c) With a third polypeptide containing a fourth Fc domain monomer,
d) Containing the first polypeptide, the second polypeptide, or an antigen binding domain bound to the third polypeptide.
The first Fc domain monomer and the third Fc domain monomer are combined to form a first Fc domain, and the second Fc domain monomer and the fourth Fc domain monomer are used. An Fc antigen-binding domain construct in which the bodies combine to form a second Fc domain.
JP2021500868A 2018-07-11 2019-07-11 Compositions and Methods for Modified Fc Antigen Binding Domain Constructs Targeting PD-L1 Withdrawn JP2021530989A (en)

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US201862696711P 2018-07-11 2018-07-11
US62/696,711 2018-07-11
PCT/US2019/041306 WO2020014419A2 (en) 2018-07-11 2019-07-11 Compositions and methods related to engineered fc-antigen binding domain constructs targeted to pd-l1

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JP2021530989A JP2021530989A (en) 2021-11-18
JPWO2020014419A5 true JPWO2020014419A5 (en) 2022-07-20

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KR (1) KR20210044782A (en)
CN (1) CN112996910A (en)
AU (1) AU2019299935A1 (en)
BR (1) BR112021000383A2 (en)
CA (1) CA3106108A1 (en)
IL (1) IL280038A (en)
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CA2865594C (en) * 2012-03-08 2021-07-27 Crucell Holland B.V. Human binding molecules capable of binding to and neutralizing influenza b viruses and uses thereof
US20150203591A1 (en) * 2012-08-02 2015-07-23 Regeneron Pharmaceuticals, Inc. Mutivalent antigen-binding proteins
WO2015168643A2 (en) * 2014-05-02 2015-11-05 Momenta Pharmaceuticals, Inc. Compositions and methods related to engineered fc constructs
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