JP6668241B2 - 予測可能で、一貫性のある、且つ再現可能な糖型特性を示すFc含有分子 - Google Patents
予測可能で、一貫性のある、且つ再現可能な糖型特性を示すFc含有分子 Download PDFInfo
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- JP6668241B2 JP6668241B2 JP2016540433A JP2016540433A JP6668241B2 JP 6668241 B2 JP6668241 B2 JP 6668241B2 JP 2016540433 A JP2016540433 A JP 2016540433A JP 2016540433 A JP2016540433 A JP 2016540433A JP 6668241 B2 JP6668241 B2 JP 6668241B2
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- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
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Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
- C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
- C07K2317/41—Glycosylation, sialylation, or fucosylation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/524—CH2 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/71—Decreased effector function due to an Fc-modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/72—Increased effector function due to an Fc-modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Description
本出願は、参照によって本明細書に組み入れられる2013年9月5日に出願されたUS61/874,222号の利益を主張する。
本出願は、ASCII形式で電子的に提出されており、その全体が参照によって本明細書に組み入れられる配列表を含有する。2014年9月5日に作成された前記ASCIIコピーはA−1859−WO−PCT_SL.txtと名付けられ、98,304バイトのサイズである。
定義
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(配列番号1)である。
CH3ドメインに相当するVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(配列番号4)。
YTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(配列番号5)である。
Fc含有ポリペプチド
S239DとV264D
任意のさらなる修飾
S239D/I332E
S239D/A330S/I332E
S239D/A330L/I332E
S298A/D333A/K334A
P247I/A339D
P247I/A339Q
D280H/K290S
D280H/K290S/S298D
D280H/K290S/S298V
F243L/R292P/Y300L
F243L/R292P/Y300L/P396L
F243L/R292P/Y300L/V305I/P396L
G236A/S239D/I332E
K326A/E333A
K326W/E333S
K290E/S298G/T299A
K290N/S298G/T299A
K290E/S298G/T299A/K326E
K290N/S298G/T299A/K326E
K334V
L235S+S239D+K334V
Q311M+K334V
S239D+K334V
F243V+K334V
E294L+K334V
S298T+K334V
E233L+Q311M+K334V
L234I+Q311M+K334V
S298T+K334V
A330M+K334V
A330F+K334V
Q311M+A330M+K334V
Q311M+A330F+K334V
S298T+A330M+K334V
S298T+A330F+K334V
S239D+A330M+K334V
S239D+S298T+K334V
L234Y+K290Y+Y296W
L234Y+F243V+Y296W
L234Y+E294L+Y296W
L234Y+Y296W
K290Y+Y296W
N297A(IgG1)
L234A/L235A(IgG1)
V234A/G237A(IgG2)
L235A/G237A/E318A(IgG4)
H268Q/V309L/A330S/A331S(IgG2)
C220S/C226S/C229S/P238S(IgG1)
C226S/C229S/E233P/L234V/L235A(IgG1)
L234F/L235E/P331S(IgG1)
S267E/L328F(IgG1)。
操作された抗体及びFc融合タンパク質をコードするポリヌクレオチド
医薬組成物
キット
実施例1
結果
[Fc変異体mAbは予想された折り畳みを示す]
実施例2
[N−グリコシル化操作のための位置の選択]。
[DNA構築物、細胞培養、形質移入、増幅及び産生]。
[MAbの精製及び定量]。
[MAb生成物の質的解析]。
[親水性相互作用クロマトグラフィ(HILIC−MS)−グリカンマッピング法]。
[示差走査熱量測定(DSC)]。
[Fc変異体のFcγRIIAへの相対的な結合の測定]
[FcRnのAlphaScreenに基づく結合アッセイ]。
[マウスにおける薬物動態(PK)試験]
結果
[mAbのグリカンのプロセッシングに影響を与える残基の選択]
Claims (20)
- Fc内で2以上のアミノ酸置換を含むFc含有分子であって、前記FcがS239D及びV264L、S239D及びV264D、又はS239D及びD265Aの置換の組み合わせを含み、及び、前記FcがヒトIgG1又はヒトIgG2に由来する、前記Fc含有分子。
- 前記Fcが、配列番号1又は配列番号5で示されるアミノ酸配列に対して少なくとも90%同一であるアミノ酸配列を含む、請求項1に記載のFc含有分子。
- 前記Fc含有分子が抗体又はFc融合タンパク質である、請求項1〜2のいずれか一項に記載のFc含有分子。
- 前記Fc含有分子がN結合型グリコシル化を含む、請求項1〜3のいずれか一項に記載のFc含有分子。
- 前記Fc含有分子が哺乳類宿主細胞における発現によってグリコシル化される、請求項4に記載のFc含有分子。
- 前記哺乳類宿主細胞がチャイニーズハムスター卵巣(CHO)細胞株である、請求項5に記載のFc含有分子。
- Fc含有分子の40%を超えるものが成熟N結合型グリコシル化を含む、請求項4〜6のいずれか一項に記載のFc含有分子を含む組成物。
- Fc含有分子の50%未満が未成熟のN結合型グリコシル化を含む、請求項4〜7のいずれか一項に記載のFc含有分子を含む組成物。
- Fc含有分子の5%未満がマンノース5(M5)N結合型グリコシル化を含む、請求項4〜8のいずれか一項に記載の組成物。
- 前記組成物が医薬組成物である、請求項7〜9のいずれか一項に記載の組成物。
- 請求項10に記載の医薬組成物を含むバイアル。
- 請求項10に記載の医薬組成物を含む注射器。
- Fc領域を含むポリペプチドであって、前記Fc領域がS239D及びV264L、S239D及びV264D、又はS239D及びD265Aの置換の組み合わせを含み、及び、前記Fc領域がヒトIgG1又はヒトIgG2に由来する、前記ポリペプチド。
- 請求項13に記載のポリペプチドをコードする核酸。
- プロモータに作動可能に連結されている請求項14に記載の核酸を含む発現ベクター。
- 請求項14に記載の1以上の核酸を含む宿主細胞。
- 前記核酸がプロモータに作動可能に連結される請求項16に記載の宿主細胞。
- 前記宿主細胞がチャイニーズハムスター卵巣(CHO)細胞株である、請求項16に記載の宿主細胞。
- Fc含有分子の産生方法であって、前記方法が
(a)Fc含有ポリペプチドの発現を生じる条件下で請求項16〜18のいずれか一項に記載の宿主細胞を培養することと、
(b)前記培養物から前記Fc含有分子を単離することと
を含む、前記方法。 - Fc含有分子の組成物の製造方法であって、前記方法が
(a)Fc含有ポリペプチドの発現を生じる条件下で請求項16〜18のいずれか一項に記載の宿主細胞を培養することと、
(b)前記培養物から前記Fc含有分子を単離してFc含有分子の組成物を得ることと
を含む、前記方法。
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MX341925B (es) | 2010-03-29 | 2016-09-07 | Zymeworks Inc | Anticuerpos con funcion efectora suprimida o mejorada. |
US8722044B2 (en) | 2011-03-15 | 2014-05-13 | Janssen Biotech, Inc. | Human tissue factor antibody and uses thereof |
TW201326209A (zh) | 2011-09-30 | 2013-07-01 | Chugai Pharmaceutical Co Ltd | 具有促進抗原清除之FcRn結合域的治療性抗原結合分子 |
WO2013180295A1 (ja) | 2012-06-01 | 2013-12-05 | 日本電信電話株式会社 | パケット転送処理方法およびパケット転送処理装置 |
US9300829B2 (en) | 2014-04-04 | 2016-03-29 | Canon Kabushiki Kaisha | Image reading apparatus and correction method thereof |
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EP3041863A1 (en) | 2016-07-13 |
EP3041863A4 (en) | 2017-08-16 |
US20160207980A1 (en) | 2016-07-21 |
US20230235024A1 (en) | 2023-07-27 |
JP2016531581A (ja) | 2016-10-13 |
US11427627B2 (en) | 2022-08-30 |
EP3712166A1 (en) | 2020-09-23 |
AU2014318017B2 (en) | 2020-02-06 |
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