HRP20150444T1 - Trovalentna, bispecifiäśna protutijela - Google Patents
Trovalentna, bispecifiäśna protutijela Download PDFInfo
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- HRP20150444T1 HRP20150444T1 HRP20150444TT HRP20150444T HRP20150444T1 HR P20150444 T1 HRP20150444 T1 HR P20150444T1 HR P20150444T T HRP20150444T T HR P20150444TT HR P20150444 T HRP20150444 T HR P20150444T HR P20150444 T1 HRP20150444 T1 HR P20150444T1
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- 108090000765 processed proteins & peptides Proteins 0.000 claims 14
- 102000004196 processed proteins & peptides Human genes 0.000 claims 11
- 229920001184 polypeptide Polymers 0.000 claims 10
- 125000000539 amino acid group Chemical group 0.000 claims 6
- 230000035772 mutation Effects 0.000 claims 4
- 239000000427 antigen Substances 0.000 claims 3
- 102000036639 antigens Human genes 0.000 claims 3
- 108091007433 antigens Proteins 0.000 claims 3
- 235000001014 amino acid Nutrition 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 2
- 239000004475 Arginine Substances 0.000 claims 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims 1
- 239000004473 Threonine Substances 0.000 claims 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims 1
- 235000004279 alanine Nutrition 0.000 claims 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 235000018417 cysteine Nutrition 0.000 claims 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims 1
- 102000039446 nucleic acids Human genes 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 150000007523 nucleic acids Chemical class 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims 1
- 239000004474 valine Substances 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- 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
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- 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
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Claims (11)
1. Trovalentno, bispecifično protutijelo, naznačeno time, da obuhvaća
a) protutijelo u punoj duljini, koje se specifično veže na prvi antigen i sastoji se od dva jaka lanca protutijela i dva slaba lanca protutijela;
b) polipeptid koji se sastoji od sljedećih:
ba) varijabilna domena jakog lanca protutijela (VH); ili
bb) varijabilna domena jakog lanca protutijela (VH) i konstantna domena 1 protutijela (CH1), pri čemu je navedeni polipeptid staljen s N-završetkom od VH-domene preko peptidne poveznice na C-završetak od jednog između dva jaka lanca od navedenog protutijela pune duljine;
c) polipetid koji se sastoji od sljedećih:
ca) varijabilna domena slabog lanca protutijela (VL); ili
cb) varijabilna domena slabog lanca protutijela (VL) i konstantna domena 1 slabog lanca protutijela (CL), pri čemu je navedeni polipeptid staljen s N-završetkom od VL-domene preko peptidne poveznice na C-završetak od preostalog između dva jaka lanca od nevedenog protutijela pune duljine;
i pritom varijabilna domena jakog lanca protutijela (VH) od polipeptida pod točkom b) i varijabilna domena slabog lanca protutijela (VL) od polipeptida pod točkom c), zajedno tvore mjesto vezanja antigena, gdje se specifično vežu na drugi antigen.
2. Trovalentno, bispecifično protutijelo prema zahtjevu 1, naznačeno time, da se CH3-domena od jednog jakog lanca i CH3-domena od drugog jakog lanca, sastaju na sučelju koje obuhvaća originalno sučelje između CH3-domena od protutijela;
pri čemu se navedeno sučelje mijenja u svrhu pokretanja tvorbe trovalentnog, bispecifičnog protutijela, gdje je ta promjena naznačena time, da se
i) mijenja CH3-domena od jednog jakog lanca,
tako da se unutar originalnog sučelja CH3-domena od jednog jakog lanca koji se sastaje s originalnim sučeljem od CH3-domene od drugog jakog lanca unutar trovalentnog, bispecifičnog protutijela,
zamjenjuje aminokiselinski ostatak s aminokiselinskim ostatkom koji ima veći volumen bočnog lanca, čime se generira izbočenje unutar sučelja od CH3-domene od jednog jakog lanca, koje se može pozicionirati u šupljini unutar sučelja od CH3-domene od drugog jakog lanca,
i
ii) mijenja CH3-domena od drugog jakog lanca,
tako da se unutar originalnog sučelja od druge CH3-domene koja se sastaje s originalnim sučeljem od prve CH3-domene unutar trovalentnog, bispecifičnog protutijela,
zamjenjuje aminokiselinski ostatak s aminokiselinskim ostatkom koji ima manji volumen bočnog lanca, čime se generira šupljina unutar sučelja od druge CH3-domene, u kojoj se može pozicionirati izbočenje unutar sučelja od prve CH3-domene.
3. Trovalentno, bispecifično protutijelo prema zahtjevu 1, naznačeno time, da se
i) navedeni aminokiselinski ostatak koji ima veći volumen bočnog lanca, odabire iz skupine koju čine arginin (R), fenilalanin (F), tirozin (Y), triptofan (W); i
ii) navedeni aminokiselinski ostatak koji ima manji volumen bočnog lanca, odabire iz skupine koju čine alanin (A), serin (S), treonin (T), valin (V).
4. Trovalentno, bispecifično protutijelo prema zahtjevima 2 ili 3, naznačeno time, da se obje CH3-domene dalje mijenjaju pomoću uvođenja cisteina (C) kao aminokiseline, na odgovarajućim pozicijama od svake CH3-domene, tako da se može stvoriti disulfidni most između obje CH3-domene.
5. Trovalentno, bispecifično protutijelo prema bilo kojem od zahtjeva 2 do 4, naznačeno time, da CH3-domena pod točkom i) sadrži mutaciju T366W; i CH3-domena pod točkom ii) sadrži mutacije: T366S, L368A, Y407V.
6. Trovalentno, bispecifično protutijelo prema zahtjevu 4, naznačeno time, da CH3-domena pod točkom i) sadrži mutacije: Y349C, T366W; i CH3-domena pod točkom ii) sadrži mutacije: S354C, T366S, L368A, Y407V.
7. Trovalentno, bispecifično protutijelo prema bilo kojem od zahtjeva 1 do 6, naznačeno time, da su varijabilna domena jakog lanca protutijela (VH) od polipeptida pod točkom b) i varijabilna domena slabog lanca od protutijela (VL) od polipeptida pod točkom c), povezane i stabilizirane preko međulanca disulfidnog mosta pomoću uvođenja disulfidne veze između sljedećih pozicija:
i) pozicija 44 varijabilne domene jakog lanca prema poziciji 100 varijabilne domene slabog lanca,
ii) pozicija 105 varijabilne domene jakog lanca prema poziciji 43 varijabilne domene slabog lanca, ili
iii) pozicija 101 varijabilne domene jakog lanca prema poziciji 100 varijabilne domene slabog lanca.
8. Trovalentno, bispecifično protutijelo prema zahtjevu 7, naznačeno time, da su varijabilna domena jakog lanca protutijela (VH) od polipeptida pod točkom b) i varijabilna domena slabog lanca od protutijela (VL) od polipeptida pod točkom c), povezane i stabilizirane preko međulanca disulfidnog mosta pomoću uvođenja disulfidne veze između sljedećih pozicija:
i) pozicija 44 varijabilne domene jakog lanca prema poziciji 100 varijabilne domene slabog lanca.
9. Trovalentno, bispecifično protutijelo prema zahtjevu 6, naznačeno time, da su peptidne poveznice pod točkama b) i c), identični peptidi s duljinom između 25 i 50 aminokiselina.
10. Farmaceutski sastav, naznačen time, da obuhvaća trovalentno, bispecifično protutijelo prema zahtjevima od 1 do 9.
11. Nukleinska kiselina, naznačena time, da kodira trovalentno, bispecifično protutijelo prema zahtjevima od 1 do 9.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09005108 | 2009-04-07 | ||
| EP10712365.5A EP2417156B1 (en) | 2009-04-07 | 2010-04-01 | Trivalent, bispecific antibodies |
| PCT/EP2010/002122 WO2010115589A1 (en) | 2009-04-07 | 2010-04-01 | Trivalent, bispecific antibodies |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20150444T1 true HRP20150444T1 (hr) | 2015-05-22 |
Family
ID=40942481
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20150444TT HRP20150444T1 (hr) | 2009-04-07 | 2015-04-24 | Trovalentna, bispecifiäśna protutijela |
Country Status (21)
| Country | Link |
|---|---|
| US (4) | US20100256340A1 (hr) |
| EP (1) | EP2417156B1 (hr) |
| JP (2) | JP5616428B2 (hr) |
| KR (1) | KR101456326B1 (hr) |
| CN (1) | CN102369214B (hr) |
| AR (1) | AR076193A1 (hr) |
| AU (1) | AU2010234031B2 (hr) |
| BR (1) | BRPI1010297A2 (hr) |
| CA (1) | CA2757931C (hr) |
| CY (1) | CY1116376T1 (hr) |
| DK (1) | DK2417156T3 (hr) |
| ES (1) | ES2537100T3 (hr) |
| HR (1) | HRP20150444T1 (hr) |
| IL (1) | IL214884A (hr) |
| MX (1) | MX2011010168A (hr) |
| PL (1) | PL2417156T3 (hr) |
| PT (1) | PT2417156E (hr) |
| SG (1) | SG175077A1 (hr) |
| SI (1) | SI2417156T1 (hr) |
| TW (1) | TW201039850A (hr) |
| WO (1) | WO2010115589A1 (hr) |
Families Citing this family (285)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2592271T3 (es) | 2005-03-31 | 2016-11-29 | Chugai Seiyaku Kabushiki Kaisha | Métodos de producción de polipéptidos mediante la regulación de la asociación de los polipéptidos |
| EP4342995A3 (en) | 2006-03-31 | 2024-05-15 | Chugai Seiyaku Kabushiki Kaisha | Methods for controlling blood pharmacokinetics of antibodies |
| EP4218801A3 (en) | 2006-03-31 | 2023-08-23 | Chugai Seiyaku Kabushiki Kaisha | Antibody modification method for purifying bispecific antibody |
| AR068563A1 (es) | 2007-09-26 | 2009-11-18 | Chugai Pharmaceutical Co Ltd | Region constante de anticuerpo mutante |
| WO2009041643A1 (ja) | 2007-09-26 | 2009-04-02 | Chugai Seiyaku Kabushiki Kaisha | Cdrのアミノ酸置換により抗体の等電点を改変する方法 |
| US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
| WO2010107110A1 (ja) | 2009-03-19 | 2010-09-23 | 中外製薬株式会社 | 抗体定常領域改変体 |
| EP3674317A1 (en) | 2009-03-19 | 2020-07-01 | Chugai Seiyaku Kabushiki Kaisha | Antibody constant region variant |
| JP5501439B2 (ja) | 2009-04-02 | 2014-05-21 | ロシュ グリクアート アクチェンゲゼルシャフト | 完全長抗体と単鎖Ｆａｂフラグメントとを含む多重特異的抗体 |
| MX2011010166A (es) * | 2009-04-07 | 2011-10-11 | Roche Glycart Ag | Anticuerpos biespecificos anti-erbb-3/anti-c-met. |
| JP5616428B2 (ja) | 2009-04-07 | 2014-10-29 | ロシュ グリクアート アクチェンゲゼルシャフト | 三価の二重特異性抗体 |
| US9676845B2 (en) | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
| US8703132B2 (en) * | 2009-06-18 | 2014-04-22 | Hoffmann-La Roche, Inc. | Bispecific, tetravalent antigen binding proteins |
| US9493578B2 (en) | 2009-09-02 | 2016-11-15 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
| WO2011034605A2 (en) | 2009-09-16 | 2011-03-24 | Genentech, Inc. | Coiled coil and/or tether containing protein complexes and uses thereof |
| WO2011037158A1 (ja) | 2009-09-24 | 2011-03-31 | 中外製薬株式会社 | 抗体定常領域改変体 |
| EP2543730B1 (en) | 2010-03-04 | 2018-10-31 | Chugai Seiyaku Kabushiki Kaisha | Antibody constant region variant |
| TW201138821A (en) | 2010-03-26 | 2011-11-16 | Roche Glycart Ag | Bispecific antibodies |
| WO2011147834A1 (en) | 2010-05-26 | 2011-12-01 | Roche Glycart Ag | Antibodies against cd19 and uses thereof |
| KR20150013949A (ko) | 2010-07-19 | 2015-02-05 | 에프. 호프만-라 로슈 아게 | 항암요법에 반응할 가능성이 증가된 환자를 확인하는 방법 |
| EP2596362A1 (en) | 2010-07-19 | 2013-05-29 | F. Hoffmann-La Roche AG | Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy |
| WO2012010582A1 (en) | 2010-07-21 | 2012-01-26 | Roche Glycart Ag | Anti-cxcr5 antibodies and methods of use |
| WO2012016227A2 (en) | 2010-07-29 | 2012-02-02 | Xencor, Inc. | Antibodies with modified isoelectric points |
| BR112013002532A2 (pt) | 2010-08-05 | 2016-05-31 | Hoffmann La Roche | proteína de fusão de citocina anti-viral do anticorpo anti-mhc |
| WO2012025530A1 (en) | 2010-08-24 | 2012-03-01 | F. Hoffmann-La Roche Ag | Bispecific antibodies comprising a disulfide stabilized - fv fragment |
| US9217039B2 (en) * | 2010-11-01 | 2015-12-22 | Symphogen A/S | Anti-HER3 antibodies and compositions |
| PT2644698T (pt) | 2010-11-17 | 2018-01-31 | Chugai Pharmaceutical Co Ltd | Molécula multiespecífica de ligação ao antigénio com uma função alternativa à função do fator viii de coagulação do sangue |
| JP5766296B2 (ja) | 2010-12-23 | 2015-08-19 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | ポリペプチド−ポリヌクレオチド複合体、およびエフェクター成分の標的化された送達におけるその使用 |
| US10689447B2 (en) | 2011-02-04 | 2020-06-23 | Genentech, Inc. | Fc variants and methods for their production |
| MX355255B (es) * | 2011-02-04 | 2018-04-11 | Genentech Inc | Variantes de fc y métodos para su producción. |
| MX342034B (es) | 2011-02-28 | 2016-09-12 | Hoffmann La Roche | Proteinas monovalentes que se unen a antigenos. |
| RU2607038C2 (ru) | 2011-02-28 | 2017-01-10 | Ф. Хоффманн-Ля Рош Аг | Антигенсвязывающие белки |
| US9624291B2 (en) | 2011-03-17 | 2017-04-18 | Ramot At Tel-Aviv University Ltd. | Bi- and monospecific, asymmetric antibodies and methods of generating the same |
| CA2828662A1 (en) | 2011-04-20 | 2012-10-26 | Roche Glycart Ag | Method and constructs for the ph dependent passage of the blood-brain-barrier |
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