navigating the patent maze

Stem Cells Inc. has announced that they have been granted a U.S. patent for neural stem cells. PHOSITA has a comprehensive post about it.

The Public Patent Foundation filed a request to the US Patent and Trademark Office to institute a re-examination of the most recently issued U.S. “Axel patent”, which is owned by Columbia University. The Axel patents essentially claim co-transformation of eukaryotic cells. Three prior Axel patents earned hundreds of millions of dollars for Columbia University, but expired in the year 2000. The most recent patent, US Patent No. 6,455,275 (the ‘275 patent), was granted in September 2002, and claims co-transformation of CHO cells. CHO cells are often used in production of recombinant medicines, such as EPO. Because the filing date of the ‘275 patent was 7 June 1995, the patent term is 17 years from the date of issuance. This patent will not expire until September 2019. It is no surprise then that this patent is currently the subject of at least 8 separate litigations brought by mostly big pharmaceutical companies, who are trying to get the patent revoked by courts.

The major basis of the litigations and the re-examination request is the same: the USPTO should have rejected the patent claims for “obviousness type double patenting”. This type of double patenting means that the claims of the second patent are obvious in view of the first patent and thus, are not patentable. It is possible for an applicant to overcome such a rejection by “disclaiming” any part of the patent term that extends beyond the first patent and declaring that the two patents are owned by the same person or company. If Columbia University had agreed to file the disclaimer, the newest patent would also have expired in 2000. Instead they were able to successfully argue against the double patenting rejection.

Recourse through either the court system or the Patent Office will take time, so do not expect a quick resolution of this issue.

The Public Patent Foundation is a non-profit organization that “represents the public’s interests against wrongly issued patents and unsound patent policy” according to its web site. A copy of the re-exam request can be viewed here.

Cancer Research UK has announced the grant of European Patent No: EP 868 467 B1 and moreover, that public laboratories will be able to use the claimed invention without charge. Interestingly, the press release from Cancer Research neglects to state that Duke University is a co-owner of the patent. A related patent was granted in the year 2000 in the United States (US 6045997), although the claims of the two patents differ.

The BRCA1 and BRCA2 genes have been implicated in breast cancer development. Patents on the genes BRCA1 and BRCA2 and diagnosis based on mutations of these genes have prompted substantial public criticism of the granting of patents for human genes. Myriad Genetics, Inc. in Salt Lake City, UT holds many patents in the U.S. and Europe and markets a test for diagnosis of and predisposition to breast cancer. At least one of the European patents is still being opposed (a procedure whereby one challenges the patentability of the claims).

The latest Cancer Research patent claims specific nucleic acid sequences of the exons of a splice variant of BRCA2 and alleles. The full-length cDNA molecule is only claimed as the result of a detailed procedure for cloning. Full-length protein sequences and fragments are also covered. The key claim however, appears to be Claim 16, which claims a method of diagnosing a susceptibility or predisposition to breast, ovarian and prostate cancers by direct sequence analysis of nucleic acid or polypeptide or by PCR to screen for normal or mutant BRCA2 genes in patient samples.

In the U.S. patent, the claims are directed to the exon sequences or portions of those sequences that are at least 20 bases long and peptide sequences or fragments. There are no diagnosis claims, however. Presumably, there are still pending patent applications in the U.S. with claims to diagnosis.

It remains to be seen whether the European patent will be opposed. Oppositions can be filed up to 9 months after the grant date. It also remains to be determined what is the relationship of the patents of Myriad Genetics and Cancer Research and whether this new patent will affect the ability of Myriad to market their test.

.

U.S. Patent number 4,569,794, claims fusion protein purification technique known commonly as “His Tag”. This patent and its foreign counterparts was recently licensed to Inproteo, formerly known as the Indiana Proteomics Consortium, from Eli Lilly and Company. Inproteo has the exclusive right to issue sub-licenses. It is rumored to be in negotiations with several biotech companies. So far two licenses have been announced, one to Biogen (7 Oct 2003) and one to Genentech (21 Jan 2004). Terms are not publicized however.

U.S. Patent 4,569,794 issued to Eli Lilly on 11 Feb 1986. Its patent term expires 17 years from date of issuance — 11 Feb 2003. Thus, it appears that this patent is no longer in force. How is it possible then that Inproteo is licensing it? Court decisions in the United States have unambiguously declared that royalties cannot be collected on an expired patent. One answer may be that licenses are being granted for non-US patents. The expiration date of those patents would be 21 November 2005.

The first claim in the European patent EP 184355 B1 is:

A compound comprising a biologically active polypeptide or protein covalently linked to a peptide that is able to chelate an immobilized divalent metal ion and that has two to five amino acid residues, at least one of which is selected from the group of histidine and cysteine.

On the face of it, this claim appears to be rather narrow, requiring that the tag is from 2-5 amino acids. The corresponding claim in the U.S. lacked a limitation for length of peptide tag as well as lacked a limitation for the composition of the tag. Most researchers use a His6 tag, which falls outside the literal wording of the European claim, but wouldn’t have fallen outside the scope of the U.S. claim.

Another main claim in the European patent encompasses the method.

A process for separating a biologically active polypeptide or protein in the form of its precursor from a mixture containing said precursor and impurities, which comprises contacting said precursor with a resin containing immobilized metal ions, said precursor comprising the biologically active polypeptide or protein covalently linked to a peptide that is able to chelate an immobilized divalent metal ion, binding said precursor to said resin, and selectively eluting said precursor from said resin, and wherein
said peptide comprises at least one amino acid selected from the group consisting of histidine and
cysteine.

This claim does not have a limitation on the length of the tag sequence, only that at least one of the amino acids in the tag be either histidine or cysteine. The corresponding U.S. claim was similarly worded but again did not contain a limitation for the composition of the peptide tag.

It’s interesting that this very broad patent on what many may feel is a basic research tool has escaped the attention of either the press or the “anti-patent” groups.

Briston-Myers Squibb, a US pharmaceutical firm, has given up its patent in Thailand protecting the anti-retroviral drug didanosine (ddi) in tablet form, marketed under the tradename Videx. The patent was granted in 1998. Activists in Thailand had pursued legal action for two years to get the patent revoked. About one million Thais have been infected with HIV over the last 20 years.

The drug has been produced in powdered form by the Government Pharmaceutical Organization, but the tablet form has advantages of convenience and consistant dosage. Now, any factory in Thailand will be able to produce the drug in tablet form. The price is expected to drop from 3,000 baht (about USD 77) to less than 900 baht per month. The drug is used in combination with other drugs to treat AIDS.