Analytical Chemistry Experts in Patent Litigation

Understanding When and How to Use Analytical Chemistry

Shri Thanedar, Ph.D., CEO and Chief Scientist
Ross Faith, J.D., Litigation Support Specialist

The Problem: Understanding When and How to Use Chemical Analysis in Patent Cases

Patent litigators encounter many different types of cases involving varied branches of science throughout their careers.  When a case involving the chemistry of a product, such as a pharmaceutical product, is at issue, the patent litigator may have only a hazy idea of which experts to call on to help further her client’s claim or defense.  The attorney will likely encounter cases involving issues of chemical composition infrequently and therefore may lack a network of experts who deal with chemical analysis problems.  Analytical chemistry laboratories with litigation support practices offer one solution that may work for these attorneys.

Scientists in analytical chemistry study the separation, identification, and quantification of the chemical components of natural and artificial materials.[1] Analytical chemists can provide significant support to litigators involved in patent disputes by breaking down the chemical composition of a product to demonstrate whether the product infringes on a patent and explaining their theory to a jury.

This paper explains the background and nature of this area of science and explores the role that experts in this area can play in resolving a complex patent case.

Analytical Chemistry: The Science

Analytical chemistry has been around for many years, with the first use of instrumental techniques dating back to the 1860s.[2] Modern analytical chemistry labs use instrumental methods almost exclusively.  These methods include: chromatography, spectroscopy, microscopy, molecular characterization, and testing of thermal and mechanical properties.[3] These methods can be used to deformulate (separating and identifying chemicals in a composition) a sample, identify contaminants, provide a product defect analysis, or test for materials identification and physical and thermal properties, among other services.[4]

Analytical Chemistry in Litigation – A Case Study of In re Omeprazole Patent Litigation

Background

In re Omeprazole Patent Litigation demonstrates the significant role that chemical analysis expert witnesses can play in a high stakes patent dispute.  In that case, the issue was whether several pharmaceutical manufacturers had violated AstraZeneca’s patent for its blockbuster drug, Prilosec, where the competing pharmaceutical companies marketed drugs to address heartburn with the key ingredient in Prilosec, omeprazole.[5]

AstraZeneca holds patents for an omeprazole formulation under the name Prilosec.[6] AstraZeneca claimed that several manufacturers were infringing two of the patents (the ‘505 and ‘230 patents).  The alleged infringers included: Mylan Laboratories, Inc. and Mylan Pharmaceuticals, Inc. (“Mylan”), Esteve Quimica, S.A. and Laboratorios Dr. Esteve, S.A. (“Esteve”), Apotex Corp., Apotex, Inc., and Torpham, Inc. (“Apotex”), Lek Pharmaceutical and Chemical Company D.D. and Lek USA , Inc. (“Lek”), and Impax Laboratories, Inc. (“Impax”).[7] The district court held that Mylan, Esteve, and Lek did not infringe on AstraZeneca’s patents, while Apotex and Impax did infringe claims of both patents.[8]

The role of chemical analysis experts in the case

The case turned on the testimony of more than 15 expert witnesses, many of whom had analytical chemistry backgrounds.[9] AstraZeneca’s claim against Lek provides an illustrative example of how the court used these experts to resolve the various patent claims.   Lek filed an Abbreviated New Drug Application (“ANDA”) with the Food and Drug Administration (“FDA”), seeking approval for its 10-mg and 20-mg dosage of “Omeprazole Delayed Release Capsules,” which were generic versions of AstraZeneca’s Prilosec.[10] One issue was whether Lek’s products had an alkaline reacting compound (“ARC”) or its equivalent.[11]

In order to resolve the competing claims, the court examined testimony of expert witnesses for AstraZeneca and Lek.  For AstraZeneca, the court accepted Dr. Martyn Davies as an expert in the testing, analysis, and characterization of drug formulations; Dr. Robert Langer as an expert in drug delivery and pharmaceutical dosage forms; and Dr. Klibanov as an expert in pharmaceutical chemistry and pharmaceutical formulation chemistry.[12] For Lek, the court accepted Dr. Gary Christian as an expert in analytical chemistry; Dr. Phillip E. Russell as an expert in microsopy and microanalysis; Dr. John Coates as an expert in attenuated total reflectance Fourier Transform-Infrared Spectroscopy (“ATR-FTIR”), analytical chemistry, and spectral data handling; Dr. Brian Herman as an expert in fluorescent spectroscopy and optical microscopy; Dr. Yuval Garini as an expert in optical microsopy  and spectroscopy, including fluorescence microscopy and confocal laser scanning microscopy; and Dr. Albert Padwa as an expert organic and heterocyclic chemistry.[13]

To determine whether there was an ARC, the court needed to know what the pH of the composition was.  It was necessary for the court to find that the pH was alkaline in order to find that there was an ARC in the composition.  Analytical chemistry helped resolve this question.  Both Dr. Davies for the AstraZeneca and the Dr. Christian for Lek tested the pH of the omeprazole alone and pH after adding a small sample of water to the mixture of omeprazole and excipients that compose the core of Lek’s product.[14] Both scientists found that the mixture with water had an acidic composition, but each came to a different conclusion about the omeprazole alone.  The court concluded that the appropriate measure was the reading of the mixture with water because there was no discussion in the patent of measuring the pH of omeprazole alone.[15] The court also held that the readings of the omeprazole alone were too inconsistent to warrant a conclusion that it was alkaline.[16]

Finally, the court had to determine whether the addition of methylamine (“MA”), a colorless gas derivative of ammonia, to the solution resulted in an ARC.  Again, analytical chemistry was instrumental in deciding the issue.  Dr. Padwa claimed that Lek added MA during the crystallization process to purify the omeprazole in the manufacturing process.[17] Dr. Davies asserted that the purpose of the MA is to “[help] stabilize the omeprazole.”[18] Because MA is an alkaline organic base, if it survived the manufacturing process, then Lek’s formulation could be said to contain an ARC.  To determine whether the MA survived, the court evaluated a mass spectrometry reading from Dr. Davies.  After significant testimony on both sides, the court concluded that Lek had cast sufficient doubt on Dr. Davies’ particular use of mass spectrometry warranted a conclusion that the final product contained MA.[19] As a result, AstraZeneca’s claim against Lek was dismissed.

Conclusion

As the Omeprazole case demonstrates, patent cases often benefit from chemical analysis expert witnesses.  When the chemical formula must be broken down and separated in order to understand the nature of an alleged infringer’s product, chemical analysts with expertise in instrumentation such as mass spectrometry can shape the outcome of the case.  Analytical chemistry labs that use a problem-solving approach can help attorneys to identify when chemical analysis expert witness services are needed.

For more information related to this white paper, please visit /litigation-support.


[1] Holler, F. James; Skoog, Douglas A.; West, Donald M. (1996). Fundamentals of analytical chemistry. Philadelphia: Saunders College Pub. ISBN 0-03-005938-0.

[2] ANALYTICAL SCIENCES 2001, VOL.17 SUPPLEMENT, Basic Education in Analytical Chemistry

[3] For an extended discussion of these methods and the instrumentation behind them, see /about-us/methods.

[4] For more, see /services.

[5] In re Omeprazole Patent Litigation, 490 F.Supp.2d 381 (S.D.N.Y. 2007).

[6] Id. at 391.

[7] Id. at 390.

[8] Id. at

[9] Id. at 402-12.

[10] Id. at 448.

[11] Id.

[12] Id. at 402.

[13] Id. at 405-406

[14] Id. at 451-54.

[15] Id. at 453.

[16] Id. at 454-55.

[17] Id. at 456.

[18] Id. at 455.

[19] Id. at 462.