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Last Updated: March 29, 2024

Claims for Patent: 8,410,259


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Summary for Patent: 8,410,259
Title:Recombinant expression vector elements (REVES) for enhancing expression of recombinant proteins in host cells
Abstract: Compositions and methods comprising recombinant expression vector elements (rEVEs) to enhance the level of expression of recombinant proteins are described. Other compositions and methods for lowering, substantially suppressing, or essentially silencing expression of a recombinant protein are also described.
Inventor(s): Gion; Wendy R. (Charlton, MA), Carson; Gerald R. (Belmont, MA), Gao; Hong (Allston, MA), Kunes; Yune Z. (Winchester, MA)
Assignee: AbbVie Inc. (North Chicago, IL)
Application Number:13/098,337
Patent Claims:1. A yeast host cell comprising a recombinant vector, wherein the recombinant vector comprises a recombinant expression vector element (rEVE) polynucleotide molecule comprising a nucleotide sequence selected from the group consisting of: the nucleotide base sequence of SEQ ID NO:1, the nucleotide base sequence of SEQ ID NO:2, a sequence complementary to any foregoing sequence, an expression-enhancing portion of any foregoing sequence, and combinations thereof; and wherein the yeast host cell is selected from the group consisting of: Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, Schizosaccharomyces pombe, and Yarrowia lipolytica.

2. A nematode host cell comprising a recombinant vector, wherein the recombinant vector comprises a recombinant expression vector element (rEVE) polynucleotide molecule comprising a nucleotide sequence selected from the group consisting of: the nucleotide base sequence of SEQ ID NO:1, the nucleotide base sequence of SEQ ID NO:2, a sequence complementary to any foregoing sequence, an expression-enhancing portion of any foregoing sequence, and combinations thereof; and wherein the nematode host cell is Caenorhabditis elegans.

3. A prokaryotic host cell comprising a recombinant vector, wherein the recombinant vector comprises a recombinant expression vector element (rEVE) polynucleotide molecule comprising a nucleotide sequence selected from the group consisting of: the nucleotide base sequence of SEQ ID NO:1, the nucleotide base sequence of SEQ ID NO:2, a sequence complementary to any foregoing sequence, an expression-enhancing portion of any foregoing sequence, and combinations thereof; and wherein the prokaryotic host cell is selected from the group consisting of: Escherichia coli, a serovar of Salmonella enterica, a Shigella species, Wollinella succinogenes, Proteus vulgaris, Proteus mirabilis, Edwardsiella tarda, Citrobacter freundii, a Pasteurella species, a Haemophilus species, a Pseudomonas species, a Bacillus species, a Staphyloccocus species, and a Streptococcus species.

4. A method of producing a recombinant protein of interest comprising: inserting into a host cell a recombinant expression vector wherein the recombinant expression vector comprises: one or more genes encoding the recombinant protein of interest; and a nucleotide base sequence selected from the group consisting of: the nucleotide base sequence of SEQ ID NO:1, the nucleotide base sequence of SEQ ID NO:2, a sequence complementary to any foregoing sequence, an expression-enhancing portion of any foregoing sequence, and combinations thereof; and culturing the host cell under conditions promoting expression of the recombinant protein of interest.

5. The method according to claim 4, wherein said recombinant protein of interest is selected from the group consisting of a soluble protein, a membrane protein, a structural protein, a ribosomal protein, an enzyme, a zymogen, an antibody molecule, a cell surface receptor protein, a transcription regulatory protein, a translation regulatory protein, a chromatin protein, a hormone, a cell cycle regulatory protein, a G protein, a neuroactive peptide, an immunoregulatory protein, a blood component protein, an ion gate protein, a heat shock protein, a dihydrofolate reductase (DHFR), an antibiotic resistance protein, a functional fragment of any of the preceding proteins, an epitope-containing fragment of any of the preceding proteins, and combinations thereof.

6. The method according to claim 5, wherein the antibody molecule is selected from the group consisting of an antibody to an immunoregulatory protein, an antibody to a selectin, an antibody to a cell surface receptor, and a dual variable domain immunoglobulin (DVD-Ig) molecule.

7. The method according to claim 6, wherein the antibody to an immunoregulatory protein is an anti-IL-13 antibody or an anti-TNF-.alpha. antibody.

8. The method according to claim 7, wherein the anti-TNF-.alpha. antibody is adalimumab.

9. The method according to claim 6, wherein the antibody molecule is a dual variable domain immunoglobulin (DVD-Ig) molecule.

10. The method according to any one of claims 4-9, wherein the recombinant expression vector comprises at least one copy of a gene encoding a dihydrofolate reductase.

11. The method according to any one of claims 4-9, wherein the host cell is selected from the group consisting of: a Chinese Hamster Ovary (CHO) cell, a COS cell, a Vero cell, an SP2/0 cell, an NS/0 myeloma cell, a human embryonic kidney (HEK 293) cell, a baby hamster kidney (BHK) cell, a HeLa cell, a human B cell, a CV-1/EBNA cell, an L cell, a 3T3 cell, an HEPG2 cell, a PerC6 cell, and an MDCK cell.

12. The method according to claim 11, wherein the recombinant expression vector comprises at least one copy of a gene encoding a dihydrofolate reductase.

Details for Patent 8,410,259

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Abbvie Inc. HUMIRA adalimumab Injection 125057 12/31/2002 ⤷  Try a Trial 2027-03-30
Abbvie Inc. HUMIRA adalimumab Injection 125057 02/21/2008 ⤷  Try a Trial 2027-03-30
Abbvie Inc. HUMIRA adalimumab Injection 125057 04/24/2013 ⤷  Try a Trial 2027-03-30
Abbvie Inc. HUMIRA adalimumab Injection 125057 09/23/2014 ⤷  Try a Trial 2027-03-30
Abbvie Inc. HUMIRA adalimumab Injection 125057 11/23/2015 ⤷  Try a Trial 2027-03-30
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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