Momenta Pharmaceuticals, Inc. (MNTA)

[investorgold2002]

Copaxone Characterization

I should say I am no expert in chemistry..I did a bit of digging to kinda understand this better.

Basically there is another patent pending application from Momenta

http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=2&f=G&l=50&co1=AND&d=PG01&s1=copaxone&s2=momenta&OS=copaxone+AND+momenta&RS=copaxone+AND+momenta

If you read this, you will get an idea on how they go about characterizing product and proving structural sameness criteria(3)
mentioned in FDA's response to citizen's petition on lovenox

1) Basically they test various random samples of commercial copaxone manufactured with process mentioned in the original 1974 patent
(TEVA uses same process). Per that patent that product (as in RTM label) has manufacturing/measurement variance of +/- 25%

2) They measure their identified structural signature (in this case amount of Pyro-gluco content) during the test. They basically
found for any commercial product manufactured by following process mentioned in 74 patent(as described above in step 1) within specified manufacturing/measure allowance, the Pyro-gluco content is b/w 2500-6500 ppm

3) Keep in mind, molar mass(5,000-9,000kda) and amino acid composition(Amino acid ratio: Tyrosine: 0.098; Alanine: 0.435; Lysine 0.343; glutamic acid: 0.141 ) of Product could be the same as Copaxone, but yet fail to satisfy
"sameness" criteria described in Step 2). See the quote from this patent
"both deviating samples A and B were outside of the range for pyro-Glu content determined for Copaxone.RTM.. Sample A was within the range for Copaxone.RTM. molar mass and amino acid composition"


The indian company looks like has come up with a different process of making a product with same molar mass and amino acid
composition as Copaxone.
However, the product cannot be guaranteed to be the same as Copaxone unless they come up with a new structural signature and prove that
structural signature identifies commercial product manufactured by process mentioned in 74 patent which TEVA uses within specified tolerance
I don't think Nacto/Mylan will be able to get their ANDA application anywhere without this.


Below I have quoted relevant section of the patent
"Example 5

Pyro-Glu Content can Distinguish Glatiramer Acetate

[0047]Using the method described in Example 3, the pyro-Glu content of commercial Copaxone.RTM. was compared to several other copolymer samples.
A sample of glatiramer acetate (M-GA) prepared according to the method described in U.S. Pat. No. 3,849,550 was evaluated for pyro-Glu content.
Table 2, below, provides the results of the analysis of a number of compositions, this sample conforms to the range found for pyro-Glu content from a sampling of Copaxone.RTM. lots, or between 2500-6500 ppm.

TABLE-US-00002 TABLE 2 Analysis of Samples Analysis of Samples Molecular Amino acid P-Glu weight (Mp) composition content Sample (Da)
(avg. molar fraction).sup.2 (ppm) Copaxone .RTM. 5,000-9,000.sup.1 0.141 L-Glutamic acid 2500-6500 0.427 L-alanine ppm.sup.4 0.095 L-tyrosine 0.338 L-lysine Glatiramer acetate 8407 (conforms).sup.3 4900 ppm sample (M-GA) (conforms) (conforms) Deviating sample A 6579 (conforms).sup.3 8200 ppm (conforms) (fails) Deviating sample B 4808 (conforms).sup.3 7500 ppm (fails) (fails) .sup.1Molecular weight range specified in Copaxone .RTM. product label and prescription information .sup.2Average molar fraction target specified in Copaxone .RTM. product label and prescription information .sup.3Conforms relative to specification range based on label target plus allowance for manufacturing and measurement variability .sup.4Range is 75%/125% of Copaxone min/max for 30 commercial samples

[0048]To test the ability of pyro-Glu content to distinguish glatiramer acetate from non-conforming copolymers, two control copolymers were tested. The control copolymers were made with deliberate and specific deviations in the timing of NCA addition or in the duration of step 2. As shown in Table 1, both deviating samples A and B were outside of the range for pyro-Glu content determined for Copaxone.RTM.. Sample A was within the range for Copaxone.RTM. molar mass and amino acid composition while Sample B failed molar mass but conformed in amino acid composition. This data shows that evaluation of pyro-Glu content can identify differences in materials and process not observed by looking at molar mass and amino acid composition alone and illustrates the ability of pyro-Glu measurement to identify non-conforming copolymer. Accordingly, pyro-Glu content can be used to evaluate product and process quality for glatiramer acetate. "