Aventis Pharma S.A. v. Amphastar Pharmaceuticals, Inc.

525 F.3d 1334, 87 U.S.P.Q. 2d (BNA) 1110, 2008 U.S. App. LEXIS 10357, 2008 WL 2039065
CourtCourt of Appeals for the Federal Circuit
DecidedMay 14, 2008
Docket2007-1280
StatusPublished
Cited by25 cases

This text of 525 F.3d 1334 (Aventis Pharma S.A. v. Amphastar Pharmaceuticals, Inc.) is published on Counsel Stack Legal Research, covering Court of Appeals for the Federal Circuit primary law. Counsel Stack provides free access to over 12 million legal documents including statutes, case law, regulations, and constitutions.

Bluebook
Aventis Pharma S.A. v. Amphastar Pharmaceuticals, Inc., 525 F.3d 1334, 87 U.S.P.Q. 2d (BNA) 1110, 2008 U.S. App. LEXIS 10357, 2008 WL 2039065 (Fed. Cir. 2008).

Opinions

PROST, Circuit Judge.

This infringement case returns to us for the second time after remand to the district court on the issue of whether Aventis committed inequitable conduct before the United States Patent and Trademark Office (“PTO”). In our earlier opinion, we held that the dosage of the prior art composition used in half-life comparisons with the patented composition was information material to patentability, but we remanded to the district court to determine whether ' there was an intent to deceive by Aventis in failing to disclose the dosage. After a trial on the matter, the district court found that there was intent to deceive and held the patents unenforceable for inequitable conduct. Because we find no abuse of discretion by the district court in its holding of inequitable conduct, we affirm.

I

Aventis is the owner of U.S. Patent No. RE 38,743 (“the '743 patent”) and U.S. Patent No. 5,389,618 (“the '618 patent”), which was surrendered upon the issuance of the '743 Patent. The patents are directed to a composition comprising low molecular weight heparins (“LMWHs”). Claim 1 of the '618 patent recites:

A heterogeneous intimate admixture of sulfated heparinic polysaccharides, such sulfated polysaccharides having a weight average molecular weight less than that of heparin and said admixture consisting essentially of
from 9% to 20% of polysaccharide chains having a molecular weight less than 2,000 daltons
from 5% to 20% of polysaccharide chains having a molecular weight greater than 8,000 daltons, and
from 60-86% of polysaccharide chains having a molecular weight of between 2,000 and 8,000 daltons,
the ratio between the weight average molecular weight and the number average molecular weight thereof ranging from 1.3 to 1.6
said admixture (i) exhibiting a bioa-vailability and antithrombotic activity greater than heparin and (ii) having an average molecular weight of between approximately 3,500 and 5,500 daltons.

The drug is marketed as Lovenox® in the United States and Clexane® in Europe and is effective in preventing thromboses (blood clotting) while minimizing the possibility of hemorrhaging, especially during high-risk surgery. According to the specification, the advantage of the claimed LMWHs as compared to heparin is that they exhibit a longer half-life, excellent bioavailability, higher rate of absorption, low clearance, resistance to degradation, increased residence time, and reduced sensitivity to serum factors. '618 patent, col. 2,1. 55-col. 3,1. 26.

A

The prosecution history of the '618 patent is germane to the issue of inequitable conduct. Original claim 1 of the '618 patent application recited as follows:

A heterogeneous intimate admixture of sulfated heparinic polysaccharides, such sulfated polysaccharides having a weight [1338]*1338average molecular weight less that that of heparin and which comprise from 9% to 20% of polysaccharide chains having a molecular weight less than 2,000 daltons and from 5% to 20% of polysaccharide chains having a molecular weight greater than 8,000 daltons, the ratio between the weight average molecular weight and the number average molecular weight thereof ranging from 1.3 to 1.6.

In the first office action, the patent examiner rejected the claims under 35 U.S.C. §§ 102(b)/103 over several references, including European Patent 40,144 (“EP 144”). The examiner stated that each of the prior art references teaches sulfated heparinic admixtures within the molecular weight (“MW”) range of the claims and is considered to be inherently the same as the claimed admixtures. In particular, the examiner explained that

the Patent and Trademark Office does not have facilities for testing and comparing various products, and where the prior art teaches a product which is identical or nearly identical to that claimed, it is incumbent upon the Applicant to convincingly demonstrate that the claimed product provides some unexpected or unobvious property not demonstrated by the prior art products.

(Emphases added).

In response to the office action, Aventis independently addressed the anticipation and obviousness portion of the rejection.1 With respect to anticipation, Aventis argued that EP 144 does not expressly state that the mixture contains two types of polysaccharides, one with a MW less than 2,000 daltons and one with a MW greater than 8,000 daltons, nor does it state the number average/weight average MW ratio. Presuming, therefore, that the examiner’s anticipation rejection rested on inherency, Aventis argued that the evidence in the specification rebuts inherency. In particular, Aventis pointed to example 6 in the specification, which provides in relevant part:

This example illustrates the increase in stability, in vivo, of the mixtures of the invention, expressed by their plasma half-life.
(1) From the mixtures produced in Examples 3 and 4:
40 mg dose: in 75% of the cases, the half-life was longer than 4 hours, and was even longer than 4% hours in approximately 45% of the cases;
60 mg dose: in 75% of the cases, the half-life was longer than 3.7 hours.
(3) When the product was prepared according to the process described in European Patent EP 40,144, the half-life was longer than 4% hours in 17% of the cases.

'618 patent, col. 9, 11. 33-58 (emphases added). Example 6 was prepared with the assistance of Dr. André Uzan, a French chemist who was a non-inventor. Based on the example, Aventis argued that the claimed LMWHs exhibit a significantly longer half-life than formulations prepared in accordance with EP '144. Aventis went on to explain that, because it is well established that compounds are inseparable from their properties, the evidence of a difference in a property, i.e., half-life, serves as evidence of a difference in structure. With regard to the obviousness portion of the rejection, Aventis contended that, under 35 U.S.C. § 103, the prior art must suggest the modification to one of skill in the art, yet EP '144 provides absolutely no suggestion to select the particular combination of oligosaccharide chains of specified lengths as claimed.

[1339]*1339The examiner was not convinced and issued a second (final) office action, maintaining the prior 102/103 rejection “for the reasons of record in the last Office action.” The examiner reiterated that the MW requirements of the claimed compounds are within the range of the compounds disclosed in EP '144 and that any properties would be inherent in the prior art compounds because they have the same structure as the claimed compounds.2

Thereafter, Aventis amended claim 1 to read:

A heterogeneous intimate admixture of sulfated heparinic polysaccharides, such sulfated polysaccharides having a weight average molecular weight less that that of heparin and said admixture comprising [3]

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525 F.3d 1334, 87 U.S.P.Q. 2d (BNA) 1110, 2008 U.S. App. LEXIS 10357, 2008 WL 2039065, Counsel Stack Legal Research, https://law.counselstack.com/opinion/aventis-pharma-sa-v-amphastar-pharmaceuticals-inc-cafc-2008.