The Claim Game

Patent Claim Analysis: Nuclear Factors Associated with Transcriptional Regulation

Today I am going to discuss the key patent claims involved in Ariad Pharmaceuticals et al. v. Eli Lilly and Company.

Case Background: In this case, Ariad Pharma accused Eli Lilly of infringing on a patent regarding to Eli Lilly's osteoporosis medication and sepsis treatment. Though the lower court ruled in favor of Ariad, the appellate court reversed this decision, finding that the patent claims at hand were invalid due to lack of written description.

Patent at issue: The patent at issue is US6410516 B1: Nuclear Factors Associated with Transcriptional Regulation. In this patent, the inventors claim the method of NF-kB, a transcription factor, that activates gene expression in the body's immune responses to infection.

The first 10 Patent claims follow:

1. A method for inhibiting expression in a eukaryotic cell

of a gene whose transcription is regulated by NF-.kappa.KB
the method comprising reducing NF-.kappa.B activity
in the cell such that expression of said gene is inhibited.

A method inhibiting gene expression of genes regulated by NF-.kappa.B.

2. A method for selectively inhibiting expression

in a eukaryotic cell
of genes whose transcription is regulated by NF-.kappa.B
the method comprising reducing NF-.kappa.B activity
in the cell such that expression of said genes is inhibited

A method selectively inhibiting gene expression of genes regulated by NF-.kappa.B.

3. A method for reducing the level of expression of a viral gene

whose transcription is regulated by NF-.kappa.B in a eukaryotic cell
the method comprising reducing NF-.kappa.B activity
in the cell such that expression of said viral gene is reduced.

A method reducing viral gene expression of viral genes regulated by NF-.kappa.B.

4. The method of claim 3,

wherein the viral gene is a cytomegalovirus (CMV),
human immunodeficiency virus (HIV)
or simian virus 40 (SV40) gene.

A method reducing viral gene expression of a CMV, HIV, SV40 genes regulated by NF-.kappa.B.

5. A method for reducing the level of expression

of a cytokine gene
whose transcription is regulated by NF-.kappa.B
in a eukaryotic cell
comprising reducing NF-.kappa.B activity in the cell
such that expression of said cytokine gene is reduced.

A method reducing gene expression of a cytokine gene regulated by NF-.kappa.B.

6. A method for diminishing induced NF-.kappa.B-mediated intracellular signaling

comprising reducing NF-.kappa.B activity in cells
such that NF-.kappa.B-mediated intracellular signaling is diminished.

A method for diminishing induced NF-.kappa.B-mediated intracellular signaling.

7. A method for modifying effects of external influences on a eukaryotic cell

which external influences induce NF-.kappa.B-mediated intracellular signaling
the method comprising altering NF-.kappa.B activity in the cells
such that NF-.kappa.B-mediated effects of external influences are modified.

A method for modifying the impact of extracellular influences that induce NF-.kappa.B-mediated intracellular signaling.

8. The method of claim 7

wherein NF-.kappa.B activity in the cell is reduced.

A method for modifying the impact of extracellular influences that induce NF-.kappa.B-mediated intracellular signaling such that NF-.kappa.B activity is reduced.

9. A method for reducing, in eukaryotic cells, the level of expression of genes

which are activated by extracellular influences which induce NF-.kappa.B-mediated intracellular signaling,
the method comprising reducing NF-.kappa.B activity in the cells
such that expression of said genes is reduced.

A method for reducing gene expression of genes activated by extracellular influences that induce NF-.kappa.B-mediated intracellular signaling.

10. A method for reducing the effects of bacterial infection on mammalian cells

comprising reducing NF-.kappa.B activity in mammalian cells
so as to reduce bacterial lipopolysaccharide-induced gene expression in the mammalian cells.

A method for reducing the effects of bacterial infection on mammalian cells that reduces NF-.kappa.B activity in said cells.

Taken together, these claims, along with the rest of the patent describe methods of modifying genes involved in NF-.kappa.B activity to inhibit, reduce, or modify in a particularized way, NF-.kappa.B activity. Though the claims are very particular about the cells in which or the genes involved with NF-.kappa.B activity, the claims fail to elaborate on the methods of reducing/inhibiting/modifying. The failure to write a written description describing these methods led the appellate court to declare the claims as invalid, finding Eli Lilly to not have infringed on Ariad's patents.

Sources:
http://www.casebriefs.com/blog/law/intellectual-property-law/intellectual-property-keyed-to-merges/patent-law-intellectual-property-keyed-to-merges/ariad-pharmaceuticals-inc-v-eli-lilly-co/
http://patft.uspto.gov/netacgi/nph-Parser?Sect2=PTO1&Sect2=HITOFF&p=1&u=/netahtml/PTO/search-bool.html&r=1&f=G&l=50&d=PALL&RefSrch=yes&Query=PN/6410516
http://www.washingtonpost.com/wp-dyn/content/article/2006/05/04/AR2006050401787.html

Gene Patents: Association for Molecular Pathology v. Myriad Genetics

One of the more recent, significant patent litigation cases within biotechnology is the Association for Molecular Pathology v. Myriad Genetics decided by the Supreme Court in 2013.

In this case, the Association for Molecular Pathology challenged Myriad Genetics for its patents relating to BRCA1 and BRCA2 genes and particular mutations in these genes that are strongly associated with the development of breast cancer. As noted by the majority opinion in this case,

"the average American woman has a 12- to 12-percent risk of developing breast cancer, but for women with certain genetic mutations, the risk can range between 50 and 80 percent for breast cancer and between 20 and 50 percent for ovarian cancer (2)."

The specific patents in question regard mutation diagnostic methods that allowed Myriad to exclusively control diagnostic testing and scientific research on the BRCA genes. Myriad received these patents based on its research

The plaintiff, the Association for Molecular Pathology, argued that the patents on the BRCA1/2 genes are patents on products of nature. Since Section 101 of Title 35 of the United States Code defines patentable subject matter as

"any new and useful process, machine, manufacture, or compositions of matter, or any new and useful improvement thereof"

if the genes claimed are merely products of nature, they are not patent eligible. Therefore, the plaintiffs claimed that Myriad Genetics' patents are invalid based on Section 101. Myriad's defense is based on the argument that its patents are valid because once a gene is isolated, it is distinguishable from other genes.

Additionally, the plaintiffs noted that Myriad's exclusivity in regards to BRCA research is an impediment to further scientific research.

This case originated at the district court, which ruled in favor of the Association for Molecular Pathology, invalidating Myriad Genetics BRCA patents. Myriad appealed this case to the U.S. Court of Appeals for the Federal Circuit. The appeal court reversed the district court decision and held Myriad's patents valid on the grounds that isolated genes are chemically and structurally distinct from genes in the body. The Association for Molecular Pathology appealed this decision to the U.S. Supreme Court where in a unanimous 9-0 decision, SCOTUS decided that naturally occurring gene sequences are not patent eligible, however gene sequences that are not occurring in nature are indeed patent eligible. This decision reverses in part and affirms in part the decision of the appeals court.

To understand the two-fold implications of this Supreme Court decision, some molecular biology background is required. Genes are sequences of DNA. This case sets the precedent that naturally occurring sequences of DNA cannot be patented because they are products of nature, and merely isolation does not, on its own, make these sequences of DNA patent eligible. However, there are sequences of DNA that are not occurring naturally in nature. The prime example of these sequences include cDNA. cDNA is DNA that is made in laboratory settings, excluding introns - noncoding regions of DNA.

Therefore, this decision sets precedent for gene patents in that naturally occurring sequences cannot be patented, however cDNA can be patented.

Sources:
(1) https://www.ocf.berkeley.edu/~edy/genomics/cdna.jpg
(2) https://www.oyez.org/cases/2012/12-398
(3) http://i2.cdn.turner.com/cnnnext/dam/assets/130523190137-sulik-myriad-genetics-protest-horizontal-large-gallery.jpg