EP0259904A1
Expired / Lapsed
EP
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Advanced anticancer therapy and cytotoxic medicaments for its implementation
Assignee: Intracel Corp
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Filing: 1987-08-05
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Granted: —
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Expires: 2007-08-05
Abstract
Abstract A therapeutic composition comprising a chemical conjugate including a first moiety, other than an immunoglobulin or fragment thereof, such as epidermal growth factor, which preferentially binds to a tumor cell, and is internalized by the cell, and a second moiety linked to the first moiety, and comprising a biodegradable polymeric carrier, such as polyglutamic acid, to which one or more cytotoxic molecules, for instance, daunomycin, are attached. The degradation of the carrier by intracellular enzymes releases a cytotoxic agent, resulting in selective destruction of the tumor cells.
Inventors
- 👤 Andrew Myers
- 👤 Daniel Bichon
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-29 17:42
CPC Classifications
A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/62; A61K47/64; A61K47/645; A61K47/642; A61P; A61P35/00
Claims Analysis
Total Claims: 41
Claim 1
Independent Claim
108 words
A therapeutic composition comprising a chemical conjugate including a first moiety, other than an immunoglobulin or fragment thereof, which preferentially binds to a tumor cell, and a second moiety linked to the first moiety, said second moiety comprising a plurality of repeated units, each unit having the structure where p and x are integers, where A x is a bifunctional linker, and where T is selected from the group consisting of free hydroxyl and a cytotoxic substance, where said units may be the same or may vary, T being a cytotoxic substance in at least one of said units, and where said conjugate is internalized by tumor cells.
Claim 2
Dependent Claim
108 words
A therapeutic composition comprising a chemical conjugate including a first moiety, other than an immunoglobulin or fragment thereof, which preferentially binds to a tumor cell, and a second moiety linked to the first moiety, said second moiety comprising a plurality of repeated units, each unit having the structure where p and x are integers, where A x is a bifunctional linker, and where T is selected from the group consisting of free hydroxyl and a cytotoxic substance, where said units may be the same or may vary, T being a cytotoxic substance in at least one of said units, and where said conjugate is internalized by tumor cells.
Claim 3
Dependent Claim
58 words
The composition of claim 1, where p is 1 or 2, where x is in the range of 0-20, where A x is an amino acid introduced to provide a functional group for convenient coupling of various cyctotoxic substances, and where if x is greater than 1, the amino acids A x may be the same or different.
Claim 4
Dependent Claim
59 words
The composition of claim 1 where the first moiety is selected from the group consisting of mouse epidermal growth factor (EGF), other animal EGF species, human EGF (also known as urogastrone), alpha-transforming growth factor (TGF), vaccinia virus growth factor (VGF), and any other peptides which bind preferentially to tumor cell receptors for EGF and are internalized by those receptors.
Claim 5
Dependent Claim
51 words
The composition of claim 1 where the first moiety is selected from the group consisting of nerve growth factor (NGF), platelet-derived growth factor (PDGF), melanocyte-stimulating hormone (MSH), thyrotropin releasing hormone (TRH), transferrin, low density lipoprotein (LDL), and any other non-immunoglobulin substances also bound by tumor cell receptors of the foregoing substances.
Claim 6
Dependent Claim
22 words
The composition of claim 1 wherein the first moiety is a substance which promotes internalization of the conjugate by a tumor cell.
Claim 7
Dependent Claim
11 words
The composition of claim 1 wherein the first moiety is EGF.
Claim 8
Dependent Claim
14 words
The composition of claim 1 where the EGF is essentially identical to human EGF.
Claim 9
Dependent Claim
17 words
The composition of claim 1 wherein the first moiety has a mitogenic effect on a tumor cell.
Claim 10
Dependent Claim
22 words
The composition of claim 1 wherein the first moiety is directly linked to the second moiety by means of a peptidyl linkage.
Claim 11
Dependent Claim
43 words
The composition of claim 2 wherein the first moiety is linked to the second moiety by a structure having the formula: where R¹ is: alkylene (C₁-C₄); 1,3-phenylene; cyclohexylene-4-methylene; or alkylene (C₁-C₄)-phenylene (1,4); R² is H, or carboxyl; and m = 1 or 2.
Claim 12
Dependent Claim
16 words
The composition of claim 1, where the molecular weight is also less than about 100,000 D.
Claim 13
Dependent Claim
19 words
The composition of claim 1, wherein T is a cytotoxic substance in at least about 10% of the units.
Claim 14
Dependent Claim
17 words
The composition of claim 1 wherein the cytotoxic substance is an inhibitor of DNA synthesis and function.
Claim 15
Dependent Claim
23 words
The composition of claim 10 wherein the cytotoxic substance is selected from the group consisting of anthracycline drugs, bleomycin, melphalan, chlorambucil, and cis-platinum.
Claim 16
Dependent Claim
19 words
The composition of claim 14 wherein the substance is selected from the group consisting of adriamycin, daunomycin, and daunorubicin.
Claim 17
Dependent Claim
17 words
The composition of claim 1 wherein the cytotoxic substance is an inhibitor of microtubule formation and function.
Claim 18
Dependent Claim
19 words
The composition of claim 16 wherein the cytotoxic substance is selected from the group consisting of vinblastine and vincristine.
Claim 19
Dependent Claim
12 words
The composition of claim 1 wherein the cytotoxic substance is an antimetabolite.
Claim 20
Dependent Claim
11 words
The composition of claim 18 wherein the cytotoxic substance is methotrexate.
Claim 21
Dependent Claim
13 words
The composition of claim 1 wherein the cytotoxic substance is a radioactive substance.
Claim 22
Dependent Claim
15 words
The composition of claim 1 wherein the cytotoxic substance is an enzymatic inhibitor of metabolism.
Claim 23
Dependent Claim
36 words
The composition of claim 21 wherein the cytotoxic substance is selected from the group consisting of the following intact proteins, subunits or modified forms thereof: Recin (particularly the A chain), diptheria toxin, Pseudomonas exotoxin, and abrin.
Claim 24
Dependent Claim
20 words
The composition of claim 1 wherein the cytotoxic substance is selected from the group consisting of aureomycin, gelonin, and hematoporphyrin.
Claim 25
Dependent Claim
11 words
The composition of claim 1 wherein the cytotoxic substance is daunomycin.
Claim 26
Dependent Claim
72 words
A therapeutic method for preferentially destroying tumor cells, comprising administering a covalent conjugate of a cytotoxic substance and a homing substance which non-immunologically and preferentially binds to tumor cells, said cytotoxic substance and said homing substance being conjugated by a polymeric carrier having a nontoxic, biodegradable, polyaminoacid backbone, and permitting said conjugate to bind to and be internalized by said tumor cells, wherein said polyaminoacid backbone is degraded, releasing said cytotoxic substance.
Claim 27
Dependent Claim
72 words
A therapeutic method for preferentially destroying tumor cells, comprising administering a covalent conjugate of a cytotoxic substance and a homing substance which non-immunologically and preferentially binds to tumor cells, said cytotoxic substance and said homing substance being conjugated by a polymeric carrier having a nontoxic, biodegradable, polyaminoacid backbone, and permitting said conjugate to bind to and be internalized by said tumor cells, wherein said polyaminoacid backbone is degraded, releasing said cytotoxic substance.
Claim 28
Dependent Claim
27 words
The method of claim 25 wherein said polyaminoacid backbone is selected to control the rate of biodegradation and hence the rate of release of the cytotoxic substance.
Claim 29
Dependent Claim
15 words
The method of claim 25 wherein said polyaminoacid backbone is preferentially degraded by tumor cells.
Claim 30
Dependent Claim
15 words
The method of claim 25 wherein the conjugate is essentially incapable of penetrating normal cells.
Claim 31
Dependent Claim
19 words
The method of claim 25 wherein said homing substance promotes the internalization of the conjugate by the tumor cells.
Claim 32
Dependent Claim
21 words
The method of claim 25 wherein the conjugate is of reduced cytotoxicity to normal cells relative to the free cytotoxic substance.
Claim 33
Dependent Claim
12 words
The method of claim 25 wherein the tumor cells are carcinoma cells.
Claim 34
Dependent Claim
13 words
The method of claim 31 wherein the tumor cells are squamous carcinoma cells.
Claim 35
Dependent Claim
21 words
The method of claim 25 wherein intracellular release of the cytotoxic substance in toxic form occurs essentially only in tumor cells.
Claim 36
Dependent Claim
21 words
The method of claim 25 wherein the conjugate also increases tumor cell metabolism, thereby increasing its sensitivity to the cytotoxic substance.
Claim 37
Dependent Claim
13 words
The method of claim 25 wherein the homing substance is epidermal growth factor.
Claim 38
Dependent Claim
49 words
A therapeutic composition consrising a chemical conjugate including a first moiety which preferntially binds to a tumor cell, a second moiety which promotes the internalization of the conjugate by the cell, and a third moiety comprising a polyaminoacid carrier and one or more cytotoxic molecules attached to said carrier.
Claim 39
Dependent Claim
49 words
A therapeutic composition consrising a chemical conjugate including a first moiety which preferntially binds to a tumor cell, a second moiety which promotes the internalization of the conjugate by the cell, and a third moiety comprising a polyaminoacid carrier and one or more cytotoxic molecules attached to said carrier.
Claim 40
Dependent Claim
16 words
The composition of claim 1, further comprising a substance which promotes the internalization of the conjugate.
Claim 41
Dependent Claim
10 words
The composition of claim 1, further comprising a mitogenic substance.
References Cited (Backward Citations)
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