HIV Antibodies
A combination of three broadly neutralizing antibodies against HIV-1 promise high potential for therapeutic and preventive use.
Polymun has generated fully human monoclonal antibodies (mAbs) against unique HIV antigens which are now widely used reference antibodies in the worldwide HIV-1 research (C2F5, C2G12 and C4E10). You can order these antibodies as research reagents.Excellent clinical phase I and phase II data were obtained in 3 different clinical trials in Europe as well as excellent data on the prevention of intravenous, intravaginal and mother-to-child virus transmission in the rhesus macaque model in the US. As a first indication we target the extension of strategic HAART interruption (STI) periods enabled by passive immunotherapy with our mAbs. Recently, an IND was filed for a phase II study in the US for treatment of chronically infected adults. A clinical study under IND of the FDA in the US was completed in August 2005 for treatment of chronically infected adults. Another phase I clinical trial is planned within the EU project EMPRO using the antibodies as a vaginally administered microbicide in a gel formulation. Broader applications are planned but deferred until sound clinical data from STI-HAART/mAb therapy trials are available.
The required clinical material for these larger trials has been already manufactured in Polymun′s own GMP-plant. Such manufacturing of biopharmaceuticals is also offered on contract basis. The economy of the mAb treatment is comparable to the currently used small-molecule antiviral therapy.
Polymun is open for strategic partnerships in clinical development and marketing.
Patents:
Human monoclonal anti-HIV-1-antibodiesgranted by: US 5,831,034
Monoclonal antibodies against HIV-1 and vaccines made thereof
granted by: CA 2,218,515; CN ZL95197896.9; EP 0 822 941 (AT CH/LI DE ES FR GB IT); MX 203743; US 5,911,989; US 6,268,484; ZA96/2629
Peptides that induce antibodies which neutralize genetically divergent HIV-1 isolates
granted by: AT 403 050; CA 2,096,159; EP 0570 357 (CH/LI DE ES FR GB IT NL PT); JP 3369246; US 5,693,752; US 5,866,694
Peptides that elicit neutralizing antibodies against genetically divergent HIV-1 strains
granted by: AU 682893; CZ 287 808; RU 2181379
Peptides mimicking a cryptic epitope of gp41 of HIV-1
granted by: AU 2002340880; EP 1 423 417 (AT BE CH/LI DE ES FR GB IE IT NL SE); JP 4243187; US 7,595,049
Antiidiotypic antibody inducing HIV-1 neutralizing antibodies
granted by: AU 2003214044; EP 1 465 928; JP 4495969; US 7,625,566
pending in: CA
Publications:
Huber M, von Wyl V, Ammann CG, Kuster H, Stiegler G, Katinger H, Weber R, Fischer M, Stoiber H, Günthard HF, Trkola A (2008) Potent HIV-Neutralizing and Complement Lysis Activity of Antibodies Are Not Obligatorily Linked. J Virol 82(8):3834-42Mehandru S, Vcelar B, Wrin T, Stiegler G, Joos B, Mohri H, Boden D, Galovich J, Tenner-Racz K, Racz P, Carrington M, Petropoulos C, Katinger H, Markowitz M (2007) Adjunctive passive immunotherapy in human immunodeficiency virus type 1-infected individuals treated with antiviral therapy during acute and early infection. J Virol 81(20):11016-31
Vcelar B, Stiegler G, Wolf H, Muntean W, Leschnik B, Mehandru S, Markowitz M, Armbruster C, Kunert R, Eibl M, Katinger H (2007) Reassessment of autoreactivity of the broadly neutralizing HIV antibodies 4E10 and 2F5 and retrospective analysis of clinical safety data. AIDS 21(16):2161-2170
Joos B, Trkola A, Kuster H, Aceto L, Fischer M, Stiegler G, Armbruster C, Vcelar B, Katinger H, Günthard H (2006) Long-Term Multiple-Dose Pharmacokinetics of Human Monoclonal Antibodies (MAbs) against Human Immunodeficiency Virus Type 1 Envelope gp120 (MAb 2G12) and gp41 (MAbs 4E10 and 2F5). Antimicrob Agents Chemother 50(5):1773-9
Trkola A, Kuster H, Rusert P, Joos B, Fischer M, Leemann C, Manrique A, Huber M, Rehr M, Oxenius A, Weber R, Stiegler G, Vcelar B, Katinger H, Aceto L, Günthard H (2005) Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies, Nature Medicine, 11(6):615-22
Zwick MB, Jensen R, Church S, Wang M, Stiegler G, Kunert R, Katinger H, Burton DR (2005) Anti-human immunodeficiency virus type 1 (HIV-1) antibodies 2F5 and 4E10 require surprisingly few crucial residues in the membrane-proximal external region of glycoprotein gp41 to neutralize HIV-1. J Virol 79(2):1252-61
Armbruster C, Stiegler G, Vcelar B, Jager W, Koller U, Jilch R, Ammann CG, Pruenster M, Stoiber H, Katinger H (2004) Passive immunization with the anti-HIV-1 human monoclonal antibody (hMAb) 4E10 and the hMAb combination 4E10/2F5/2G12. J Antimicrob Chemother 54(5):915-20
Binley JM, Wrin T, Korber B, Zwick MB, Wang M, Chappey C, Stiegler G, Kunert R, Zolla-Pazner S, Katinger H, Petropoulos CJ, Burton DR (2004) Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J Virol 78(23):13232-52
Mehandru S, Wrin T, Galovich J, Stiegler G, Vcelar B, Hurley A, Hogan C, Vasan S, Katinger H, Petropoulos CJ, Markowitz M (2004) Neutralization profiles of newly transmitted human immunodeficiency virus type 1 by monoclonal antibodies 2G12, 2F5, and 4E10. J Virol 78(24):14039-42
Ferrantelli F, Hofmann-Lehmann R, Rasmussen RA, Wang T, Xu W, Li PL, Montefiori DC, Cavacini LA, Katinger H, Stiegler G, Anderson DC, McClure HM, Ruprecht RM (2003) Post-exposure prophylaxis with human monoclonal antibodies prevented SHIV89.6P infection or disease in neonatal macaques. AIDS 17:301-9
Mascola JR, Lewis MG, VanCott TC, Stiegler G, Katinger H, Seaman M, Beaudry K, Barouch DH, Korioth-Schmitz B, Krivulka G, Sambor A, Welcher B, Douek DC, Montefiori DC, Shiver JW, Poignard P, Burton DR, Letvin NL (2003) Cellular immunity elicited by human immunodeficiency virus type 1/ simian immunodeficiency virus DNA vaccination does not augment the sterile protection afforded by passive infusion of neutralizing antibodies. J Virol 77:10348-56
Armbruster C, Stiegler GM, Vcelar BA, Jager W, Michael NL, Vetter N, Katinger H (2002) A phase Itrial with two human monoclonal antibodies (hMAb 2F5, 2G12) against HIV-1. AIDS 16:227-33
Stiegler G, Armbruster C, Vcelar B, Stoiber H, Kunert R, Michael NL, Jagodzinski LL, Ammann C, Jager W, Jacobson J, Vetter N, Katinger H (2002) Antiviral activity of the neutralizing antibodies 2F5 and 2G12 in asymptomatic HIV-1-infected humans: a phase I evaluation. AIDS 16:2019-25
Stiegler G, Kunert R, Purtscher M, Wolbank S, Voglauer R, Steindl F, Katinger H (2001) A potent cross-clade neutralizing human monoclonal antibody against a novel epitope on gp41 of human immunodeficiency virus type 1. AIDS Res Hum Retroviruses 17:1757-65
Baba TW, Lska V, Hofmann-Lehmann R, Vlasak J, Xu W, Ayehunie S, Cavacini LA, Posner, MR, Katinger H, Stiegler G, Gernacky BJ, Rizvi TA, Schmidt R, Hill LR, Keeling ME, Lu Y, Wright JE, Chou TC, Ruprecht RM (2000) Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian human immunodeficiency virus infection. Nat Med 6:200-206
Mascola JR, Stiegler G, VanCott TC, Katinger H, Carpenter CB, Hanson CE, Beary H, Hayes D, Frankel SS, Birx DL, Lewis MG (2000) Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat Med 6:207-210
Mascola JR, Lewis MG, Stiegler G, Harris D, VanCott TC, Hayes D, Louder MK, Brown CR, Sapan CV, Frankel SS, Lu Y, Robb ML, Katinger H, Birx DL (1999) Protection of macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies. J Virol 73:4009-4018
Trkola A, Purtscher M, Muster T, Ballaun C, Buchacher A, Sullivan N, Srinivasan K, Sodroski J, Moore JP, Katinger H (1996) Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J Virol 70:1100-1108
Purtscher M, Trkola A, Gruber G, Buchacher A, Predl R, Steindl F, Tauer Ch, Berger R, Barrett N, Jungbauer A, Katinger H (1994) A broadly neutralizing human monoclonal antibody against gp41 of human immunodeficiency virus type 1. Aids Research and Human Retroviruses 10:1651-1658