Replies to post #61296 on Biotech Values

[DewDiligence]

Re: Lack of immunogenicity of Copaxone

>In general, smaller is better when it comes to immunogenicity, and the constituent peptides in Copaxone are very much smaller than ifn-beta (5-11 kD vs 23 kD).<

According to Millipore’s website, 8-10 kD is considered a minimum for eliciting a strong immune response; most of the constituent polypeptides in Copaxone are smaller than this.

http://www.millipore.com/immunodetection/id3/antibodiestutorial

>>
Characteristics of a Good Antigen Include:

• Areas of structural stability and chemical complexity within the molecule.
• Significant stretches lacking extensive repeating units.
• A minimal molecular weight of 8,000–10,000 Daltons, although haptens with molecular weights as low as 200 Da have been used in the presence of a carrier protein.
• The ability to be processed by the immune system.
• Immunogenic regions which are accessible to the antibody-forming mechanism.
• Structural elements that are sufficiently different from the host.
• For peptide antigens, regions containing at least 30% of immunogenic amino acids: K, R, E, D, Q, N.
• For peptide antigens, significant hydrophilic or charged residues.
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[genisi]

Copaxone antibodies - A study presented at ECTRIMS in 2006, showing that antibodies to Copaxone developed in 6 of 126 patients with MS treated with the drug, but did not interfere with the efficacy of the drug.

http://www.tevapharm.com/pr/2006/pr_634.asp

"Patients in this study (n=126) who had received COPAXONE® (glatiramer acetate injection) from 2 years to 15 years were surveyed to determine levels and types of antibodies to COPAXONE® and to correlate these parameters with treatment outcomes. Serum samples were collected from study participants, and were analyzed for the presence of antibodies to COPAXONE® using ELISA E (enzyme-linked immunosorbent assay) methodology. Clinical data, including the current and previous Expanded Disability Status Scale (EDSS) scores, and the relapse rates, were also collected at the time the serum samples were taken.

Over the mean COPAXONE® treatment period of 6.65 years, sera from only six patients demonstrated minimal in vitro neutralizing activity. In addition, patients were clinically stable for the whole COPAXONE® treatment period, showing a minimal mean increase in EDSS score of 0.65 (mean annual increase = 0.10 per patient). Despite mean disease duration of 10.75 years, the majority of patients (77 percent) surveyed had an EDSS score of less than 4.0, a stage at which they were still fully ambulatory."