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EP0506124A1 Expired / Lapsed EP ⏱️ 0.0 years remaining

Methods and substances for recruiting therapeutic agents to solid issues comprising two single chain VH-VL bifunctional binding molecules

Assignee: Tanox Inc
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Filing: 1992-03-27
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Granted: —
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Expires: 2012-03-27
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Abstract

Abstract Disclosed is a composition for enhancing delivery of a therapeutic agent to a solid tissue site, comprising: two single chain V H -V L bifunctional binding molecules which are joined together, having one specificity for a solid tissue antigen and the other for the therapeutic agent; a remover substance which binds circulating binding molecule; a therapeutic agent. The therapeutic agent is administered separately from the binding molecules and following the administration of a remover substance which aids in clearing free binding molecules in the circulation. In the preferred mode of the invention, the binding molecules have one specificity for antigens at the target site and one for the therapeutic agent. The binding molecules are adminstered and allowed time to approach a maximum concentration in the extravascular space. A remover substance, preferably a liposome conjugated with antibodies which are reactive with an antigenic epitope on the binding molecules, is then administered to remove excess binding molecules from the circulation and the extravascular space. A therapeutic agent, preferably a cytotoxic drug such as ricin A chain modified so as to enable it to enter the target cells once delivered to the target site, is then administered.

Inventors

  • 👤 Wang Chang Tse

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-10-23 15:30
CPC Classifications
C; C07; C07K; C07K16/00; C07K16/46; C07K16/468; A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/68; A61K47/6835; A61K47/6875; A61K47/6879; A61K47/69; A61K47/6905; A61K47/6911; A61K47/6913; A61K9/00; A61K9/10; A61K9/127; A61K9/1271; A61K38/00; C07K2319/00; C07K2319/33; C07K2319/55

Claims Analysis

Total Claims: 13
Claim 1
Independent Claim 55 words
A composition for enhancing delivery of a therapeutic agent to a solid tissue site, comprising: two single chain V H -V L bifunctional binding molecules which are joined together, having one specificity for a solid tissue antigen and the other for the therapeutic agent; a remover substance which binds circulating binding molecule; a therapeutic agent.
Claim 2
Dependent Claim 19 words
The composition of claim 1 wherein the remover is a liposome conjugated with antibodies specific for the binding molecules.
Claim 3
Dependent Claim 68 words
The composition of claim 1 or 2 wherein the therapeutic agent is selected from the group consisting of cytotoxic or cytolytic substances, including ricin A chain, modified Pseudomonas exotoxin A (that lacks cell binding domain and possesses translocation and ADP ribosylation activity), gelonin, abrin, diptheria toxin, pokeweed anti-viral peptide, trichothecenes, cytokines, including tumor necrosis factor ("TNF") and interleukin 1; anti-sense RNAs that inhibit the expression of tumorigenic proteins.
Claim 4
Dependent Claim 29 words
The composition of claim 1 or 2 where the therapeutic agent is ricin A chain or modified pseudomonas exotoxin A, conjugated with a membrane blending agent and a blocker.
Claim 5
Dependent Claim 12 words
Two single-chain binding molecules linked together by a small non-autologous hydrophilic peptide.
Claim 6
Dependent Claim 14 words
The linked binding molecules of claim 5 wherein the linker has a glycosylation sequence.
Claim 7
Dependent Claim 14 words
The linked binding molecules of claim 5 or 6 wherein the linker is glycosylated.
Claim 8
Dependent Claim 28 words
The linked binding molecules of any one of claims 5 to 7 wherein the linker is preferably of about 10 to about 15 amino acid residues in length.
Claim 9
Dependent Claim 28 words
The linked binding molecules of any one of claims 5 to 8 including the linker's carbohydrate moiety is linked to a non-glycosylated peptide which is non-autologous and antigenic.
Claim 10
Dependent Claim 35 words
A liposome having an antibody attached to it wherein the antibody is specific for an antigenic site associated with a linker between two single chain V H -V L binding molecules which are joined together.
Claim 11
Dependent Claim 14 words
The liposome of claim 10 wherein the antigenic site is on the peptide linker.
Claim 12
Dependent Claim 24 words
The liposome of claim 10 or 11 wherein the antigenic site is on a peptide chain attached to a carbohydrate moiety of the linker.
Claim 13
Dependent Claim 41 words
Two single chain V H -V L bifunctional binding molecules which are joined together, wherein one valency is for a tumor-associated antigen and the other is for a blocker which is linked via a membrane translocation agent to a therapeutic agent.

References Cited (Backward Citations)

WO1988009344A1 Cited
US4946778A Cited

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