Mere Hypothesis of Success is Not Reasonable Expectation of Success in Achieving the Claimed Invention

On December 18, 2017, the U.S. Court of Appeals for the Federal Circuit affirmed the District Court’s final judgement enjoining Dr. Reddy’s Laboratories and Teva Pharmaceuticals (collectively DRL) from commercially manufacturing, using, offering for sale, selling, or importing the generic version of Genzyme’s bone marrow stimulant Mozobil®. The court found that combining the prior art in the manner suggested by DRL would not create a reasonable expectation of success in achieving the claimed invention.

Genzyme, along with Sanofi Aventis, had developed a method for mobilizing and harvesting stem cells, which are immature blood cells residing in the bone marrow. Stem cells can develop into mature blood cells, including white blood cells, and are usually anchored to the bone marrow partly through a bond between a receptor (CXCR-4) located on the stem cell and a protein (SDF-1) produced in the bone marrow. Genzyme brought a Hatch-Waxman action against DRL on the basis of its’ patent which uses a combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor to increase the number of stem cells in the blood for collection (‘590 Patent). Plerixafor is the active chemical ingredient in Mozobil® .

Within the ‘590 Patent, Claim 19 was the only claim at issue. It recites a method to obtain progenitor and/or stem cells by (1) administering G-CSF to a subject; (2) administering plerixafor or a pharmaceutically acceptable salt thereof to the subject, in an amount effective to mobilize the progenitor and/or stem cells; and (3) harvesting the progenitor and/or stem cells.

After a bench trial DRL filed a motion asserting invalidity of Claim 19, citing three prior art references in support of its argument that the ‘590 Patent was invalid for obviousness:

  • First, Hendrix et al. hypothesized that the binding of plerixafor to CXCR-4 may cause the release of white blood cells from the endothelium and/or stem cells from bone marrow.
  • Second, a U.S. patent (‘304 Patent) taught a method for increasing the number of stem cells in the peripheral blood by administering both G-CSF and a blocking agent of VLA-4 antigens.
  • Third, an international patent (WO ‘814) revealed the relationship between plerixafor and white blood cell elevation.

The Federal Circuit found that combining these prior art references, as suggested by DRL, would not create a reasonable expectation of success in achieving Genzyme’s invention; In doing so, the court relied upon the following factual points found in the record:

  • CXCR-4 was in a completely different family of receptors than VLA-4.
  • The ‘304 Patent never mentioned CXCR-4, SDF-1, or plerixafor, and specifically stated that the stem cell mobilization seen with VLA-4 antagonists was due to the specific blocking of VLA-4.
  • DRL’s expert testified that a typical stem cell had around one hundred different types of receptors on its surface.
  • Claim 19 covered CXCR-1, not VLA-4.
  • There was no evidence that VLA-4 localized stem cells in the marrow like the CXCR-4/SDF-1 bond, and no expectation that VLA-4 and CSCR-4 would behave similarly concerning mobilization.
  • Hendrix et al. did not render Claim 19 obvious:
  • The hypothesis plerixafor might cause stem cell mobilization was one sentence, with no explanation,.
  • It mentioned SDF-1 and its function of attracting lymphocytes, not stem cells.
  • The discussion of CXCR-4 being widely expressed was directed to different types of white blood cells, not stem cells.
  • A skilled artisan would recognize that Hendrix never tested for the presence of stem cells.

The District Court’s finding that stem cell mobilization was highly unpredictable at the time of the invention also ran counter to an expectation of success, as there was great uncertainty about the role of SDF-1 or CXCR-4, if any, in the process of stem cell mobilization.

Finally, regarding WO ‘814, ample evidence showed that an increased white blood cell count did not necessarily correlate to stem cell mobilization. The Federal Circuit noted the gap between using plerixafor to enhance white blood cell counts and for stem cell mobilization; although DRL attempted to bridge this gap with the ‘304 Patent by analogizing plerixafor’s antagonism of CXCR-4 to the stem cell mobilizing effect of the ‘304 Patent’s anti-VLA-4 antibody, the court agreed with the district court’s rejection of this analogy.

While acknowledging the various secondary references cited by DRL, the Federal Circuit found that these did not call for a different result. Thus, the Federal Circuit affirmed the district court’s holding that the ‘590 Patent was not invalid.

 

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