G.d. Searle & Company

Other

Pharmacia Corporation

G.d. Searle LLC

Alan Michael Easton

John Patrick McKearn

Sarah Ruth Braford-Goldberg

Barbara Kure Klein

S Christopher Bauer

John Warren Thomas

Peter O Olins

Mark Allen Abrams

Kumnan Paik

Maire Helena Caparon

Peter Q Olins

John S Ng

Ping T Wang

Robert Clayton

Dean M Messing

Joseph Polazzi

Beverly Reitz

Suzanne L Bolten

Marie Helena Caparon

Leslie C Engel

Mark C Walker

Sarah Ruth Bradford-Goldberg

Maire Helen Caparon

John Patrick Mckearn

The present invention relates to a novel cytochrome P450-like enzyme (11 alpha hydroxylase) and an oxidoreductase (oxidoreductase) isolated from cDNA library generated from the mRNA ofspores. When the cDNA encoding the 11 alpha hydroxylase was co-expressed in(Sf-9) insect cells with the cDNA encoding human oxidoreductase as an electron donor, it successfully catalyzed the conversion of the steroid substrate 4-androstene-3,17-dione (AD) to 11 alpha-hydroxy-AD as determined by HPLC analysis. The invention also relates to nucleic acid molecules associated with or derived from these cDNAs including complements, homologues and fragments thereof, and methods of using these nucleic acid molecules, to generate, for example, polypeptides and fragments thereof. The invention also relates to the generation of antibodies that recognizes the11 alpha hydroxylase and oxidoreductase and methods of using these antibodies to detect the presence of these native and recombinant polypeptides within unmodified and transformed host cells, respectively. The invention also provides methods of expressing the11 alpha hydroxylase gene separately, or in combination with human oroxidoreductase, in heterologous host cells, to facilitate the bioconversion of steroid substrates to their 11 alpha hydroxy-counterparts.

[object Object]

The present invention relates to fusion molecules composed of human interleukin-3 (hIL-3) variant or mutant proteins (muteins) functionally joined to a second colony stimulating factor (CSF), cytokine, lymphokine, interleukin or IL-3 variant. These hIL-3 variants contain amino acid substitutions and may also have amino acid deletions at both the N- and C-termini. The invention also relates to pharmaceutical compositions containing the fusion molecules and methods for using them.

IL-3 variant hematopoiesis fusion protein

Aspergillus ochraceus 11 alpha hydroxylase and oxidoreductase

The present invention relates to recombinant human interleukin-3 (hIL-3) variant or mutant proteins (muteins). These hIL-3 muteins contain amino acid substitutions and may also have amino acid deletions at both the N- and C-termini. The invention also relates to pharmaceutical compositions containing the hIL-3 muteins and methods for using them. Additionally, the present invention relates to recombinant expression vectors comprising nucleotide sequences encoding the hIL-3 muteins, related microbial expression systems, and processes for making the hIL-3 muteins using the microbial expression systems. Included in the present invention are deletion mutants of hIL-3 in which from 1 to 14 amino acids have been deleted from the N-terminus, and from 1 to 15 amino acids (a.a.119 to 133) have been deleted from the C-terminus, and which also contain amino acid substitutions in the polypeptide. These hIL-3 multiple mutation polypeptides may have biological activities similar to or better than hIL-3 and, in some cases, may also have an improved side effect profile.

Methods of using interleukin-3 (IL-3) mutant polypeptides for ex-vivo expansion of hematopoietic stem cells

Interleukin-3 (IL-3) multiple mutation polypeptides

The present invention relates to methods of ex-vivo expansion of hematopoietic cells by culturing hematopoietic cells in a growth medium comprising a variant of human interleukin-3 (hIL-3) which contains multiple amino acid substitutions and which may have portions of the native hIL-3 molecule deleted. The present invention also relates to the ex-vivo expansion of hematopoietic cells for gene therapy. Additionally, the present invention relates to the use of the expanded hematopoietic cells for treating patients having a hematopoietic disorder.

Methods of ex-vivo expansion of hematopoietic cells using interleukin-3 (IL-3) multiple mutation polypeptides

The present invention relates to methods of ex-vivo expansion of hematopoietic cells by culturing hematopoietic cells in a growth medium comprising a chimera protein which comprises a variant of human interleukin-3 (hIL-3) which contains multiple amino acid substitutions and which may have portions of the native hIL-3 molecule deleted and a hematopoietic growth factor. The present invention also relates to the ex-vivo expansion of hematopoietic cells for gene therapy. Additionally, the present invention relates to the use of the expanded hematopoietic cells for treating patients having a hematopoietic disorder.

Methods of ex-vivo expansion of hematopoietic cells using multivariant IL-3 hematopoiesis chimera proteins

The present invention relates to methods of ex-vivo expansion of hematopoietic cells by culturing hematopoietic cells in a growth medium comprising a variant of human interleukin-3 (hIL-3), which contains multiple amino acid substitutions and which may have portions of the native hIL-3 molecule deleted, and a hematopoietic growth factor. The present invention also relates to the ex-vivo expansion of hematopoietic cells for gene therapy. Additionally, the present invention relates to the use of the expanded hematopoietic cells for treating patients having a hematopoietic disorder.

Methods of ex-vivo expansion of hematopoietic cells using interleukin-3 mutant polypeptides with other hematopoietic growth factors

The present invention relates to human interleukin-3 (hIL-3) variant or mutant proteins (muteins) functionally co-administered with a other colony stimulating factors (CSF), cytokines, lymphokines, interleukins, hematopoietic growth factors or IL-3 variants.

Compositions for increasing hematopoiesis with interleukin-3 mutants

Co-administration of interleukin-3 mutant polypeptides with CSF's for multi-lineage hematopoietic cell production

Co-administration of interleukin-3 mutant polypeptides with CSF'S for multi-lineage hematopoietic cell production

The present invention relates to human interleukin-3 (hIL-3) variant or mutant proteins (muteins) fused with other colony stimulating factors (CSF), cytokines, lymphokines, interleukins, hematopoietic growth factors or IL-3 variants.

Methods of using multivariant IL-3 hematopoiesis fusion protein

Co-administration of interleukin-3 mutant polypeptides with CSF's or

Human interleukin-3 (IL-3) variant fusion proteins

The present invention relates to human interleukin-3 (hIL-3) variant or mutant proteins (muteins) functionally co-administered with other colony stimulating factors (CSF's), cytokines, lymphokines, interleukins, hematopoietic growth factors or IL-3 variants.

Co-administration of interleukin-3 mutant polypeptides with CSF's for

Growing community of inventors

Maryland Heights, MO, United States of America

Alan Michael Easton