University of Utah v. Max-Planck-Gesellschaft Zur Föerderung Der Wissenschaften e.V.

134 F. Supp. 3d 576, 2015 WL 5698398
CourtDistrict Court, D. Massachusetts
DecidedSeptember 28, 2015
DocketCivil Action No. 11-10484-PBS
StatusPublished
Cited by3 cases

This text of 134 F. Supp. 3d 576 (University of Utah v. Max-Planck-Gesellschaft Zur Föerderung Der Wissenschaften e.V.) is published on Counsel Stack Legal Research, covering District Court, D. Massachusetts primary law. Counsel Stack provides free access to over 12 million legal documents including statutes, case law, regulations, and constitutions.

Bluebook
University of Utah v. Max-Planck-Gesellschaft Zur Föerderung Der Wissenschaften e.V., 134 F. Supp. 3d 576, 2015 WL 5698398 (D. Mass. 2015).

Opinion

MEMORANDUM AND ORDER

Patti B. Saris, Chief United States District Judge

INTRODUCTION

This case concerns the field of RNA interference (RNAi), which is a process for inhibiting gene expression also known as “gene silencing.” RNAi plays an important role in defending cells against viruses and other diseases.1 In 2011, plaintiff University of Utah (UUtah) brought this action against Max-Planck-Gesellschaft Zur Foer-derung Der Wissenschaften e.V. (Max Planck), the Whitehead Institute for Biomedical Research (Whitehead), the Massachusetts Institute of Technology (MIT), Alnylam Pharmaceuticals, Inc. (Al-nylam), and others, seeking correction of inventorship under 35 U.S.C. § 256 (Docket No. 8). The key contention is that a UUtah faculty member, Dr. Brenda Bass, should be named a joint inventor of a family of patents known as the “Tuschl II Patents.” The defendants moved for summary judgment (Docket No. 165). After hearing, the motion is ALLOWED.2

FACTUAL BACKGROUND

The following facts are undisputed except where stated.

I. Science of RNA Interference

A brief tutorial explaining RNA interference is helpful in understanding the inven-torship dispute. The human genome is comprised of approximately 22,000 genes, each embodied as a region of deoxyribonu-cleic acid (DNA) that contains codes for the synthesis of certain proteins. DNA, which consists of building blocks known as “nucleotides,” occurs in the familiar “double helix” shape, with two strands coiled around the same axis. One end of a chain of DNA is known as the three prime (3’) end, while the other is called the five prime (5’) end.

The process by which a cell makes a protein involves two steps, transcription and translation. When a gene coding for a particular protein becomes active within a cell, the two strands of DNA for that gene unwind. During transcription, the cell reads the code in one DNA strand and produces a smp'ie-stranded chain of ribonucleic acid (RNA) called messenger RNA (mRNA), which contains the code to produce the protein. During translation, the cell reads the code in the mRNA strand and produces the protein.

[580]*580During RNAi, a form of double-stranded RNA (dsRNA) is introduced into a cell. Since RNA is typically single-stranded, this double-stranded form triggers the destruction of the dsRNA and any mRNA having a substantially similar genetic code. Once an mRNA strand is destroyed, it cannot be translated into a protein. This effectively “silences” the gene that codes for that protein and prevents it from promoting disease. The process of gene silencing has potential therapeutic value because it provides a defense against viral infections and other diseases.

II. The Tuschl I and Tuschl II Patents

The Tuschl I patents, filed by inventors Thomas Tuschl, Philip Sharp, David Bar-tel, and Philip Zamore in March 2000, involved the discovery of the molecular mechanism underlying RNAi in a Droso-phila lysate (a composition of fruit fly embryos whose cell walls have broken down).

The inventors learned that long dsRNA introduced into the Drosophila lysate were cleaved into short dsRNA fragments. Specifically, the inventors found, most of the cleavage sites occurred at intervals of 21-23 nucleotides, and short dsRNAs of this specific length that were isolated from the Drosophila lysate caused RNAi. These findings appeared in an article in the prestigious scientific journal Cell on March 31, 2000, titled “RNAi: Double-Stranded RNA Directs the ATP-Dependent Cleavage of mRNA at 21 to 23 Nucleotide Intervals.” Docket No. 182, Boebel Deck, Ex. 67. The article does not discuss the presence of 3’ overhangs on short dsRNAs, or RNase III family enzymes as they relate to the generation of short dsRNAs.

The Tuschl II patents, filed by Tuschl, Sayda Elbashir, and Winifried Lendeckel in December 2000, claim a molecule with short dsRNA fragments known as short-interfering RNA (siRNA). Claim One of U.S. Patent No. 8,372,968 reads:

An isolated double-stranded RNA molecule, which is a non-enzymatically cleaved RNA molecule, wherein:
(i) each RNA strand independently consists of 19-23 nucleotides in length, and
(ii) at least one strand has a single-stranded 3’ — overhang from 1 to 3 nucleotides,
wherein said double-stranded RNA molecule is capable of target-specific RNA interference.

Docket No. 172, Haberny Aff., Ex. 14, Column 65-66, No. 1. The underlined portion has particular significance for purposes of the present inventorship dispute. The Tuschl II patents also claim methods of preparing siRNAs with 3’ overhangs ranging from 1-5 nucleotides. One such claim reads:

A method for preparing a double stranded RNA molecule which mediates the cleavage of an mRNA in a mammalian cell, comprising
(a) synthesizing two RNA strands each having a length from 19-25 nucleotides, and
(b) combining the synthesized RNA strands under conditions suitable to form a double stranded RNA molecule, wherein said double stranded RNA molecule has a double stranded region of 14-24 nucleotides in length and one or two 3’ overhang regions of 1-5 nucleotides in length.

Haberny Aff., Ex. 11 at Column 65-66, No. 1. One key difference between the Tuschl I and Tuschl II patents is that the Tuschl II patents claim RNA molecules with 3’ overhangs that can cause RNAi in mammalian cells. See Max-Planck-Gesellschaft, 650 F.Supp.2d at 117-18. As discussed below, a description of the inventions in the Tuschl II patents was ultimately published in an [581]*581article titled “RNA interference is mediated by 21- and 22-nucleotide RNAs.”

III. Dr. Bass’s Minireview

On April 28, 2000, Dr. Brenda Bass, a tenured professor at UUtah,3 published a minireview in Cell magazine. Cell asked Bass to review the Tuschl I article published on March 31, 2000, as well as several others, and to summarize the state of RNAi research. Bass’s minireview included a prediction about how a natural enzymatic cellular process might cleave long dsRNA into the shorter dsRNA fragments described in the Tuschl I article. Specifically, Bass proposed that a certain enzyme in the RNase III family — known by the scientific community as “Dicer” — might cleave long dsRNA into siRNA. She also stated that the resulting siRNA fragments might contain one or two single-stranded nucleotides that extend beyond the double-stranded portion of the fragment at the 3’ end of the molecule, but that these 3’ overhangs would ultimately be “trimmed” to 21 and 22 nucleotide pieces. Bass stated,

If RNAi involves an RNase Ill-like enzyme, it might explain why the small RNAs observed by Zamore and Tuschl range from 21-23 nucleotides. The initial cleavage might produce dsRNAs comprised of sense and antisense 23-mers, but the 3’ overhangs would be more accessible to single-strand-specific nu-cleases present in the extract, and trimmed to 21 and 22 nucleotide pieces.

Haberny Aff., Ex. 1 at 4.

As a courtesy, Cell

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134 F. Supp. 3d 576, 2015 WL 5698398, Counsel Stack Legal Research, https://law.counselstack.com/opinion/university-of-utah-v-max-planck-gesellschaft-zur-foerderung-der-mad-2015.