EP0308936A2
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Antibody heteroconjugates for the killing of HIV-infected cells
Assignee: Bristol Myers Squibb Co
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Filing: 1988-09-22
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Granted: —
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Expires: 2008-09-22
Abstract
Abstract The present invention relates to novel antibody heteroconjugates and their use in methods for killing HIV-infected cells. The heteroconjugates are comprised of an antibody specific for an HIV antigen that is expressed on HIV-infected cells cross-linked to an antibody specific for an effector cell of the peripheral blood capable of killing an HIV-infected target cell. The antibody heteroconjugates of the invention physically bridge the effector cell to the target cell and may activate the lytic mechanism of the effector cell in the killing of the HIV-infected target cell. The methods, heteroconjugates, pharmaceutical compositions and combinations described herein provide a novel approach to the treatment of HIV-infected individuals by amplifying endogenous HIV-specific effector mechanisms and may also be of prophylactic value in individuals newly infected or accidentally exposed to the HIV virus.
Inventors
- 👤 Joyce M. Zarling
- 👤 Jeffrey A. Ledbetter
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-25 17:25
CPC Classifications
C; C07; C07K; C07K16/00; C07K16/46; C07K16/468; A; A61; A61K; A61K39/00; A61K39/395; A61K39/42; A61P; A61P31/00; A61P31/12; C07K16/08; C07K16/10; C07K16/112; C07K16/114; C07K16/1145; C07K16/18; C07K16/28; C07K16/2803; C07K16/2809; C07K16/283; A61K38/00
Claims Analysis
Total Claims: 35
Claim 1
Independent Claim
42 words
An antibody heteroconjugate comprising at least one antibody reactive with an HIV antigen expressed on the surface of an HIV-infected cell cross-linked to at least one antibody reactive with an effector cell of the peripheral blood capable of killing an HIV-infected cell.
Claim 2
Dependent Claim
42 words
An antibody heteroconjugate comprising at least one antibody reactive with an HIV antigen expressed on the surface of an HIV-infected cell cross-linked to at least one antibody reactive with an effector cell of the peripheral blood capable of killing an HIV-infected cell.
Claim 3
Dependent Claim
18 words
The antibody heteroconjugate of claim 1, wherein the HIV antigen is one found on an HIV envelope glycoprotein.
Claim 4
Dependent Claim
26 words
The antibody heteroconjugate of claim 1, wherein the effector cell is selected from the group consisting of T lymphocytes, large granular lymphocytes, granulocytes, monocytes and macrophages.
Claim 5
Dependent Claim
34 words
The antibody heteroconjugate of claim 1, wherein the effector cell-reactive antibody is selected from the group consisting of antibodies reactive with the T cell receptor on T lymphocytes and an Fc receptor on leukocytes.
Claim 6
Dependent Claim
26 words
The antibody heteroconjugate of claim 1, wherein the effector cell-reactive antibody is an antibody to the CD3 antigen on the T cell receptor of T lymphocytes.
Claim 7
Dependent Claim
25 words
The antibody heteroconjugate of claim 1, wherein the effector cell-reactive antibody is an antibody to the CD16 Fc receptor of large granular lymphocytes and granulocytes.
Claim 8
Dependent Claim
22 words
The antibody heteroconjugate of claim 1, wherein the antibodies are antibody fragments selected from the group consisting of Fab and F(ab′)₂ fragments.
Claim 9
Dependent Claim
12 words
The antibody heteroconjugate of claim 1, wherein the antibodies are chimeric antibodies.
Claim 10
Dependent Claim
40 words
An antibody heterconjugate comprising a first antibody reactive with an HIV antigen expressed on the surface of an HIV-infected cell cross-linked to a second antibody reactive with an effector cell of the peripheral blood capable of killing an HIV-infected cell.
Claim 11
Dependent Claim
40 words
An antibody heterconjugate comprising a first antibody reactive with an HIV antigen expressed on the surface of an HIV-infected cell cross-linked to a second antibody reactive with an effector cell of the peripheral blood capable of killing an HIV-infected cell.
Claim 12
Dependent Claim
18 words
Antibody heteroconjugates selected from the group consisting of 110.4 x G19-4, 110.4 x Fc2 and 41.1 x G19-4.
Claim 13
Dependent Claim
18 words
Antibody heteroconjugates selected from the group consisting of 110.4 x G19-4, 110.4 x Fc2 and 41.1 x G19-4.
Claim 14
Dependent Claim
32 words
The use of effector cells of the peripheral blood in the presence of at least one antibody heteroconjugate according to claim 1 for preparing a pharmaceutical composition for killing HIV infected cells.
Claim 15
Dependent Claim
23 words
The use of claim 11, wherein the effector cells are selected from the group consisting of peripheral blood lymphocytes, granulocytes, monocytes and macrophages.
Claim 16
Dependent Claim
17 words
The use of claim 11, wherein the effector cells are obtained from HIV seropositive or seronegative individuals.
Claim 17
Dependent Claim
25 words
The use of claim 11, wherein the effector cells are pretreated with a compound selected from the group consisting of interleukin-2, β-interferon, α-interferon and γ-interferon.
Claim 18
Dependent Claim
19 words
The use of claim 11, wherein the effector cells are pretreated with an antibody specific for the effector cells.
Claim 19
Dependent Claim
19 words
The use of claim 15, wherein the antibody is one that stimulates the lytic mechanism of the effector cells.
Claim 20
Dependent Claim
12 words
The use of claim 16, wherein the antibody is an anti-CD3 antibody.
Claim 21
Dependent Claim
33 words
The use of claim 11 or 14, wherein the effector cells are cytotoxic T lymphocytes and the antibody heteroconjugate is selected from the group consisting of 110.4 x G19-4 and 41.1 x G19-4.
Claim 22
Dependent Claim
23 words
The use of claim 11 or 14, wherein the effector cells are large granular lymphocytes and the antibody heteroconjugate is 110.4 x Fc2.
Claim 23
Dependent Claim
27 words
A pharmaceutically acceptable composition useful in the treatment of HIV infections which comprises a pharmaceutically effective amount of at least one antibody heteroconjugate according to claim 1.
Claim 24
Dependent Claim
30 words
The use of a pharmaceutically effective amount of at least one antibody heteroconjugate according to anyone of claims 1 to 10 for preparing a pharmaceutical composition for treating HIV infections.
Claim 25
Dependent Claim
27 words
The use of claim 21, wherein additionally a pharmaceutically effective amount of a compound selected from the group consisting of interleukin-2, β-interferon, α-interferon and γ-interferon is employed.
Claim 26
Dependent Claim
48 words
The use of effector cells of the peripheral blood capable of killing HIV-infected cells which effector cells were treated with at least one antibody heteroconjugate according to anyone of claims 1 to 10 in vitro and of said heteroconjugate for preparing a pharmaceutical composition for treating HIV infections.
Claim 27
Dependent Claim
25 words
The use of claim 23, wherein the effector cell is selected from the group consisting of T lymphocytes, large granular lymphocytes, granulocytes, monocytes and macrophages.
Claim 28
Dependent Claim
25 words
The use of claim 23, wherein the effector cells are pretreated with a compound selected from the group consisting of interleukin-2, β-interferon, α-interferon and γ-interferon.
Claim 29
Dependent Claim
19 words
The use of claim 23, wherein the effector cells are pretreated with an antibody specific for the effector cells.
Claim 30
Dependent Claim
19 words
The use of claim 26, wherein the antibody is one that stimulates the lytic mechanism of the effector cell.
Claim 31
Dependent Claim
12 words
The use of claim 27, wherein the antibody is an anti-CD3 antibody.
Claim 32
Dependent Claim
63 words
A process for preparing an antibody heteroconjugate having at least one first antibody reactive with an HIV antigen expressed on the surface of an HIV-infected cell cross-linked to at least one second antibody reactive with an effector cell of the peripheral blood capable of killing an HIV-infected cell, comprising the step of reacting said first and second antibody with a heterobifunctional cross-linking agent.
Claim 33
Dependent Claim
63 words
A process for preparing an antibody heteroconjugate having at least one first antibody reactive with an HIV antigen expressed on the surface of an HIV-infected cell cross-linked to at least one second antibody reactive with an effector cell of the peripheral blood capable of killing an HIV-infected cell, comprising the step of reacting said first and second antibody with a heterobifunctional cross-linking agent.
Claim 34
Dependent Claim
13 words
The process of claim 1, wherein the cross-linking agent is SPDP or GMBS.
Claim 35
Dependent Claim
40 words
The process of claim 1, wherein said first antibody is 110.4 and said second antibody is G19-4; said first antibody is 110.4 and said second antibody is Fc2; or said first antibody is 41.1 and said second antibody is G19-4.
References Cited (Backward Citations)
No citation records indexed.
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