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US4863727A Expired / Lapsed US ⏱️ 0.0 years remaining

Combination therapy using interleukin-2 and tumor necrosis factor

Assignee: Novartis Vaccines and Diagnostics Inc
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Filing: 1988-11-16
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Granted: 1989-09-05
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Expires: 2008-11-16
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Abstract

Abstract Anti-tumor activity in mammals can be augmented by administering to the mammalian host a synergistically effective amount of TNF and IL-2 or of TNF and IFN-β, or of TNF, IL-2 and IFN-β in combination. The composition of TNF and IL-2 and/or IFN-β may be prepared in vitro or administered separately to the host. If the TNF and IL-2 are administered sequentially, the TNF must be administered prior to the IL-2 to obtain synergy. The composition is useful for treating such cancers as mastocytoma, melanoma, leukemia, lymphoma, mammary adenocarcinoma, and pharyngeal squamous cell carcinoma.

Inventors

  • 👤 Robert Zimmerman
  • 👤 Jeffrey L. Winkelhake

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-04 23:07
CPC Classifications
A; A61; A61K; A61K38/00; A61K38/16; A61K38/17; A61K38/19; A61K38/20; A61K38/2013; A61K38/21; A61K38/215

Claims Analysis

Total Claims: 21
Claim 1
Independent Claim 53 words
A composition for therapeutic treatment of cancers in a mammalian host, comprising a mixture of TNF and IL-2 in synergistically effective amounts, wherein the TNF and IL-2 are from a mammalian species and said cancers are selected from the group consisting of leukemia, melanoma, mastocytoma, lymphoma, mammary adenocarcinoma, or pharyngeal squamous cell carcinoma.
Claim 2
Dependent Claim 53 words
A composition for therapeutic treatment of cancers in a mammalian host, comprising a mixture of TNF and IL-2 in synergistically effective amounts, wherein the TNF and IL-2 are from a mammalian species and said cancers are selected from the group consisting of leukemia, melanoma, mastocytoma, lymphoma, mammary adenocarcinoma, or pharyngeal squamous cell carcinoma.
Claim 3
Dependent Claim 17 words
The composition of claim 1 further comprising a pharmaceutically acceptable carrier medium for the TNF and IL-2.
Claim 4
Dependent Claim 19 words
The composition of claim 1 wherein the TNF is human or rabbit TNF and the IL-2 is human IL-2.
Claim 5
Dependent Claim 18 words
The composition of claim 3 wherein the TNF and IL-2 are recombinant, and the TNF is human TNF.
Claim 6
Dependent Claim 27 words
The composition of claim 4 wherein the TNF is a mutein with the first eight amino acids deleted and the IL-2 is des-ala 1 -IL-2 ser125 .
Claim 7
Dependent Claim 35 words
The composition of claim 5 wherein the amount of TNF is about 230-260 μg TNF per kg of host weight and the amount of IL-2 is about 15,000-800,000 units IL-2 per kg of host weight.
Claim 8
Dependent Claim 16 words
The composition of claim 4 wherein the IL-2 is attached to polyethylene glycol prior to administration.
Claim 9
Independent Claim 61 words
A method for therapeutic treatment of cancers in mammalian host comprising administering a synergistically effective amount of TNF and IL-2 wherein the TNF and IL-2 are from a mammalian species, and the administration of TNF precedes the administration of IL-2, and said cancers are selected from the group consisting of leukemia, melanoma, mastocytoma, lymphoma, mammary adenocarcinoma, or pharyngeal squamous cell carcinoma.
Claim 10
Independent Claim 61 words
A method for therapeutic treatment of cancers in mammalian host comprising administering a synergistically effective amount of TNF and IL-2 wherein the TNF and IL-2 are from a mammalian species, and the administration of TNF precedes the administration of IL-2, and said cancers are selected from the group consisting of leukemia, melanoma, mastocytoma, lymphoma, mammary adenocarcinoma, or pharyngeal squamous cell carcinoma.
Claim 11
Dependent Claim 19 words
The method of claim 8, wherein the TNF is human or rabbit TNF, and the IL-2 is human IL-2.
Claim 12
Dependent Claim 18 words
The method of claim 9 wherein the TNF and IL-2 are recombinant and the TNF is human TNF.
Claim 13
Dependent Claim 17 words
The method of claim 10 wherein the TNF and IL-2 are microbially produced and are administered parenterally.
Claim 14
Dependent Claim 27 words
The method of claim 11 wherein the TNF is a mutein with the first eight amino acids deleted and the IL-2 is des-ala 1 -IL-2 ser125 .
Claim 15
Dependent Claim 38 words
The method of claim 12 wherein the amount of TNF is about 100-1200 μg TNF per square meter of host surface and the amount of IL-2 is about 2.4-12 million units IL-2 per square meter of host surface.
Claim 16
Dependent Claim 24 words
The method of claim 13 wherein the TNF is administered daily for three days and the IL-2 is then administered daily for nine days.
Claim 17
Dependent Claim 17 words
The method of claim 14 wherein the TNF is administered intravenously and the IL-2 is administered subcutaneously.
Claim 18
Dependent Claim 14 words
The method of claim 15 wherein the host is a dog, cat or human.
Claim 19
Dependent Claim 10 words
The method of claim 15 wherein the host is human.
Claim 20
Dependent Claim 16 words
The method of claim 11 wherein the IL-2 is conjugated to polyethylene glycol prior to administration.
Claim 21
Dependent Claim 22 words
The method of claim 8 wherein the TNF and IL-2 are in admixture with a pharmaceutically acceptable carrier medium prior to administration.

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1992-09-04 1993-03-06 1993-09-05 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1996-09-04 1997-03-06 1997-09-05 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2000-09-04 2001-03-06 2001-09-05 $7700.00 Window Closed / Lapsed

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