Some argue that, unlike in IT industries, patent thickets are not problematic in pharmaceutical industry because the number of patents on a particular medicinal product is low. However, Fuzeon (enfuvirtide) shows an entangled web of patents, which may lead to high information costs in searching patents and getting licenses from patentees.
1. Orange Book
US FDA's Orange Book shows only three patents that cover Fuzeon:
(1) USP 5,464,933 "Synthetic peptide inhibitors of HIV transmission" (filing/priority date June 7, 1993);
(2) USP 6,133,418 "Synthetic peptide inhibitors of HIV transmission" (This is a division of application of '933 patent); and
(3) USP 6,475,491 "Treatment of HIV and other viral infections using combinatorial therapy" (This application is the US national phase of international application No. PCT/US96/09499, filed June 6, 1996 which is a continuation-in-part of US application No. 08/481,957 filed June 7, 1995 now abandoned.)
First two patents ('933 and '418) were granted to Duke University and the third one ('491) is owned by Trimeris. For the first '933 patent, US Federal Government has certain rights. However, there is no indication of US government interest for its division patent '418.
2. EPO INPADOC
European patent database retrieves at least nineteen (19) US patents/applications as family patents of the '933 patent. Some of them are child continuity patents/applications of '933 patent. The family patents are owned by Trimeris or Duke University or jointly. One patent ('395) is owned by individual inventors.
(1) USP 6,013,263 Measles virus peptides with antifusogenic and antiviral activities (Trimeris)
(2) USP 6,017,536 Simian immunodeficiency virus peptides with antifusogenic and antiviral activities (Trimeris)
(3) USP 6,054,265 Screening assays for compounds that inhibit membrane fusion-associated events (Trimeris)
(4) USP 6,060,065 Compositions for inhibition of membrane fusion-associated events, including influenza virus transmission (Trimeris & Duke)
(5) USP 6,068,973 Methods for inhibition of membrane fusion-associated events, including influenza virus (Trimeris)
(6) USP 6,093,794 Isolated peptides derived from the Epstein-Barr virus containing fusion inhibitory domains (Trimeris)
(7) USP 6,228,983 Human respiratory syncytial virus peptides with antifusogenic and antiviral activities (Trimeris)
(8) USP 6,333,395 Compositions for inhibition of membrane fusion-associated events, including human parainfluenza virus transmission (BARNEY SHAWN (US); LAMBERT DENNIS (US))
(9) USP 6,440,656 Methods for the inhibition of respiratory syncytial virus transmission (Trimeris)
(10) USP 6,479,055 Methods for inhibition of membrane fusion-associated events, including respiratory syncytial virus transmission (Trimeris)
(11) USP 6,518,013 Methods for the inhibition of epstein-barr virus transmission employing anti-viral peptides capable of abrogating viral fusion and transmission (Trimeris)
(12) USP 6,824,783 Methods for inhibition of membrane fusion-associated events, including HIV transmission (Duke)
(13) USP 6,951,717 Methods and compositions for inhibition of membrane fusion-associated events, including HIV transmission
(14) US 2004052820 A1 Fusion proteins comprising DP-178 and other viral fusion inhibitor peptides useful for treating aids (Duke & Trimeris)
(15) US7273614 B2 Nucleic acids encoding DP-178 and other viral fusion inhibitor peptides useful for treating aids (Duke)
(16) US2004033235 A1 Nucleic acids encoding DP-178 and other viral fusion inhibitor peptides useful for treating aids (Duke)
(17) US2007037141 A1 Methods and compositions for inhibition of membrane fusion-associated events, including HIV transmission (Trimeris)
(18) US2007202123 A1 Fusion proteins comprising DP-178 and other viral fusion inhibitor peptides useful for treating aids (Duke)
(19) US2007202127 A1 Nucleic acids encoding DP-178 and other viral fusion inhibitor peptides useful for treating aids (Trimeris)
3. License Agreement between Duke University and Trimeris
According to the license agreement of February 3, 1993 (http://www.secinfo.com/dsVsn.81Py.d.htm, of which the licensee SL-1 Pharmaceuticals, Inc is an original corporation of Trimeris), Duke University granted a worldwide exclusive license to Trimeris. Trimeris issued to the Duke University 820,000 shares of stocks in lieu of any royalty (Art. 3.01).
The license agreement specifies one invention - a US patent application No. 07/916,540 entitled "compounds which inhibit HIV replication" and filed on 20 July 1992. This application was abandoned but its continuation application was granted USP 5,656,480 and USP 6,573,078, which are neither contained in Orange Book nor retrieved from family patents of EPO INPADOC.
4. License Agreement between Trimeris and Roche
In 1999 and 2000, Trimeris reached an agreement to grant to Roche an exclusive, worldwide license for FUZEON and certain other peptide compounds in the field of HIV. Under the license agreements, Trimeris agreed to share development expenses and profits for FUZEON and certain other compounds, in the United States and Canada equally with Roche. Outside of the United States and Canada, Roche agreed to fund all development costs and pay Trimeris royalties on net sales of FUZEON and the other compounds. Through a series of amendments to the license agreements, Roche became responsible for all decisions regarding future FUZEON manufacturing volume, including management of the inventory supply chain.
The agreements between Trimeris and Roche are kept confidential and patent information involved is unknown.
5. License Agreement between Trimeris and New York Blood Center
New York Blood Center (NYBC) granted to Trimeris an exclusive, worldwide, royalty-bearing license for patents relating to certain HIV peptides. Under this license, Trimeris is required to pay the NYBC a royalty of 0.5% of net sales of FUZEON until $100 million of net sales is attained, after which the royalty reduces to 0.25%. The obligation to pay royalties to the NYBC ends on August 22, 2012.
According to NYBC, "in early 1990s, Dr. Jiang and colleagues discovered the first anti-HIV peptide derived from the HIV-1 gp41 C-terminal heptad repeat region. The patents on this discovery were licensed to Trimeris Inc., a pharmaceutical company which, in partnership with F. Hoffmann-La Roche Ltd., has developed a peptidic anti-HIV drug, Fuzeon." See http://www.nybloodcenter.org/research/index.do?sid0=7&sid1=32&page_id=31&content_id=91.
USPTO's database reveals ten patents of which Dr. Jiang is one of the inventors and NYBC is an assignee.
7,241,803 Compounds for inhibition of HIV infection by blocking HIV entry
6,727,240 Methods for preventing HIV-1 or HIV-2 infection
6,596,497 Screening of antiviral compounds targeted to the HIV-1 gp41 core structure
6,165,493 "Methods and compositions for decreasing the frequency of HIV, herpesvirus and sexually transmitted bacterial infections"
5,985,313 Method for decreasing the frequency of transmission of viral infections using cellulose acetate phthalate or hydroxypropyl methylcellulose phthalate excipients
5,985,275 .beta.-Lactoglobulin modified with aromatic anhydride compound for preventing HIV infection
5,952,009 Methods for preventing the transmission of or treating patients infected with herpesvirus
5,840,843 Synthetic polypeptides as inhibitors of HIV-1
5,798,206 Methods for screening of test compounds for inhibiting binding of a CD4-HIV 1 complex to a chemokine receptor
5,444,044 Synthetic polypeptides as inhibitors of HIV-1
6. Dispute between Novartis (Novartis Vaccines and Diagnostics, Inc.) and Trimeris/Roche
On November 2007, Novartis filed a patent infringement suit against Trimeris and Roche. Complaint of Novartis is based on its US Patent 7,285,271. See http://www.patentdocs.typepad.com/patent_docs/files/novartis_v_roche.pdf.
The '271 patent has a long history of continuation applications. The USPTO's Patent Application Information Retrieval system shows the '271 patent "is a Continuation of 08/083,391 06-28-1993 Patented 6,458,527; is a continuation of 07/931,191 08-17-1992 Abandoned; is a Division of 07/138,894 12-24-1987 Patented 5,156,949; is a Continuation-in-part of 06/773,447 09-06-1985 Abandoned; is a Continuation-in-part of
06/696,534 01-30-1985 Abandoned; is a Continuation-in-part of 06/667,501 10-31-1984 Abandoned." [Unfortunately, published document of the '271 patent contains incorrect information on the related US patent documents.]
Surprisingly enough, the first parent application of '271 patent was filed twenty-four years ago.