Synthetic transmembrane components

• US 7,052,906 B1
• Filed: 04/17/2000
• Issued: 05/30/2006
• Est. Priority Date: 04/16/1999
• Status: Expired due to Fees

• Current Assignee: Celltech Group Limited (UCB SA)
• Original Assignee: Celltech Group Limited (UCB SA)
• Inventors: Lawson, Alastair David Griffiths, Finney, Helene Margaret
• Primary Examiner(s): Li, Ruixiang
• Application Number:
  US09/958,646
• Time in Patent Office: 2,234 Days
• Field of Search: 536/234, 536/235, 536/23.1, 435/320.1, 435/325, 530/350, 514/2, 514/44
• US Class Current: 435/325
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 14/70521 CD28, CD152
• CPC Class Codes: C07K 14/70535 Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

The invention relates to nucleic acids encoding a synthetic transmembrane region as well as to membrane associated proteins containing these synthetic transmembrane regions. The design of the synthetic transmembrane region allows various properties of a protein, such as its level of expression, and relative response to ligand binding to be tailored as required for a specific purpose.

Claims

1. A nucleic acid encoding a chimeric receptor comprising

an extracellular ligand binding domain comprising a binding domain derived from a V_H or V_L antibody variable domain;

a TCRα

, TCRβ

, TCRγ

, or TRCδ

T-cell receptor variable region domain;

or a CD8α

, CD8β

, CD11A, CD11B, CD11C, CD18, CD29, CD49A, CD49B, CD49C, CD49D, CD49E, CD49F, CD61, CD41, or CD51 chain,

an extracellular spacer domain,

a synthetic transmembrane domain comprising TM24 (SEQ ID NO;

22),

and an intracellular signaling domain comprising a signaling domain derived from the zeta, eta, or epsilon chain of the T-cell receptor;

CD28;

CD4;

CD8;

the gamma chain of the Fc receptor;

or a signaling component from an interleukin, TNF, or interferon receptor, or from GMCSF, ZAP-70, fyn, lck, Itk, syk, LFA-1, LFA-2, B29, MB-1, CD3δ

, CD3γ

, CD5, or CD2.

2. A nucleic acid according to claim 1, wherein the intracellular signaling domain is synthetic.

3. A vector comprising a nucleic acid according to claim 1.

4. A chimeric receptor encoded by a nucleic acid according to claim 1.

5. An isolated host cell comprising a nucleic acid according to claim 1.

6. A composition comprising a nucleic acid according to claim 1 in conjunction with a pharmaceutically acceptable excipient.

7. A composition comprising a vector according to claim 3 in conjunction with a pharmaceutically acceptable excipient.

8. A composition comprising a chimeric receptor according to claim 4 in conjunction with a pharmaceutically acceptable excipient.

9. An isolated host cell comprising a vector according to claim 3.

10. An isolated host cell comprising a chimeric receptor according to claim 4.