Immunoglobulins directed to bacterial, viral and endogenous polypeptides
View Patent ↗Disclosed are antibodies (immunoglobulins) and fragments thereof that hydrolyze or bind polypeptide antigens belonging to Staphyloccus aureus , hepatitis C virus, human immunodeficiency virus and Alzheimer's disease. Also disclosed are novel methods to improve the antigen reactivity of the immunoglobulins and to treat a pathophysiological condition using the immunoglobulins as therapeutics.
1. An isolated or purified immunoglobulin (Ig) variable (V) domain, said immunoglobulin variable domain comprising a sequence selected from the group consisting of GL2-FR1m (SEQ ID NO: 64), GL2-FR3m (SEQ ID NO: 65), GL2-CDR1m (SEQ ID NO: 67), GL2-CDR2m (SEQ ID NO: 68), and GL2-VHm (SEQ ID NO: 63).
2. An isolated or purified immunoglobulin (Ig) variable (V) domain, said immunoglobulin variable domain comprising a sequence selected from the group consisting of 2E6 (SEQ ID NO: 8), 5D3 (SEQ ID NO: 9), 1E4 (SEQ ID NO: 10), 5H3 (SEQ ID NO: 11), 1B4 (SEQ ID NO: 30 or SEQ ID NO: 34), GL2 (SEQ ID NO: 47 or SEQ ID NO: 48), GL59 (SEQ ID NO: 53 or SEQ ID NO: 54), GL1 (SEQ ID NO: 59), JL683 (SEQ ID NO: 60), JL651 (SEQ ID NO: 61), JL606 (SEQ ID NO: 51 or SEQ ID NO: 52), JL678 (SEQ ID NO: 55 or SEQ ID NO: 56), SK18 (SEQ ID NO: 43), and SK45 (SEQ ID NO: 44).
3. The IgV domain of claim 1 , wherein said IgV domain is covalently linked to a second IgV domain to form a dimer, and wherein said dimer comprises two VL domains or two VH domains.
4. The IgV domain of claim 1 , wherein said IgV domain comprises a peptide tag at a termini.
5. The IgV domain of claim 4 , wherein the peptide tag comprises a six histidine motif.
6. The IgV domain of claim 2 , wherein said IgV domain is covalently linked to a second IgV domain to form a dimer, and wherein said dimer comprises two VL domains or two VH domains.
7. The IgV domain of claim 2 , wherein said IgV domain comprises a peptide tag at a termini.
8. The IgV domain of claim 7 , wherein the peptide tag comprises a six histidine motif.
9. The IgV domain of claim 7 , wherein the peptide tag comprises a c-Myc peptide.
10. The IgV domain of claim 7 , wherein said peptide tag is effective to reduce or to eliminate intermolecular V domain aggregation reactions.
11. The IgV domain of claim 7 , wherein the peptide tag facilitates delivery of the IgV domain(s) to an anatomic site of interest.
12. The IgV domain of claim 11 , wherein the anatomic site of interest is the blood-brain barrier.
13. The IgV domain of claim 11 , wherein the tag is putrescine, TAT peptide or an antibody to a molecule expressed on cells forming the blood-brain barrier.