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RITUXAN and AVASTIN do not infringe Sanofi’s CMV enhancer patents

The Court of Appeals for the Federal Circuit recently upheld a summary judgement decision that neither rituximab nor trastuzumab infringes two Sanofi patents (5,849,522 and 6,218,140) directed to human cytomegalovirus enhancers.  Briefly, enhancers are DNA elements capable of enhancing gene expression and find application in the pharmaceutical and biotechnology industries to increase the expression yields of protein-based products.  Representative claims of the asserted patents read as follows:

A method to increase expression of a gene in a mammalian cell comprising inserting into the mammalian cell an isolated DNA enhancer consisting of DNA from the upstream region of the
major immediate early (IE) gene of human cytomegalovirus (HCMV) and a heterologous gene that is to be expressed, wherein the DNA from the upstream region of the IE gene of HCMV is the
only HCMV material to which the mammalian cell is exposed.

A recombinant DNA plasmid comprising a DNA molecule isolated from the immediate early (IE) promoter/regulatory region of human cytomegalovirus (HCMV) and a heterologous gene positioned downstream and operatively linked to said molecule, wherein the DNA molecule enhances the transcription of DNA in an animal or mammalian host cell expression system.

Construction – Disputed Terms

  • “isolated DNA enhancer” –  The Court affirmed the district court’s construction requiring the enhancer to be separated by human intervention from the promoter DNA in its original source.  This construction was supported by statements made by the patentee to overcome art cited against a prior application in the same patent family.
  • “upstream region of the IE gene” –  The Court affirmed that this term requires the enhancer to be upstream of the HCMV IE transcription site.  The court rejected Sanofi’s construction that upstream is determined relative to the HCMV IE translation start site.
  • “plasmid” – The Court affirmed the district court’s construction of a “circular extrachromosomal molecule” and rejected Sanofi’s construction that the term also encompasses linear integrated DNA sequence. The Court’s construction was consistent with intrinsic art cited by the Examiner during prosecution and was not displaced by extrinsic art suggestive of a broader interpretation advanced by Sanofi.

Infringement

The parties had previously stipulated that “inserting”  meant “putting or introducing into”  and had also agreed that the cells lines used by the Defendants were created before the relevant patent issued. The CAFC rejected Sanofi’s argument that by propagating the relevant cell lines, the Defendants “inserted” the relevant DNA sequences into daughter cells with each round of mitosis, characterizing such arguments as contradicting “scientific understanding and common sense”.   Since the Defendants did not insert DNA into a mammalian host as required by the claims, the Court determined it need not review the Defendants’ activities in respect of the remaining claim terms.

In respect of the second patent, there was no dispute that the Defendants’ cell lines contained linear, chromosomally integrated DNA. The Court rejected Sanofi’s theory on infringement based on the doctrine of equivalents, as this theory would  “vitiate the ‘plasmid’ limitation of each asserted claim”.

A copy of the CAFC decision may be found here.