Dan asked me a ways back about who held the most
patents on new drugs: here is why I do not believe
that drug companies are the primary source of
innovation.

There is an article in the WSJ today about a lawsuit
between Eli Lilly vs 2 former NIH researchers;  I do
not have it on-line, and the site below has to do with
an earlier lawsuit involving the same drug.

http://www.ll.georgetown.edu/federal/judicial/fed/opinions/02opinions/02-1610.html

 The NIHers, who work(ed) with gene sequencing and in
this case the one for human Protein C, were asked by
Lilly for help back in the early 80's; they didn't
sign a contract, as at the time the biotech revolution
had yet to get really rolling, and scientists back
then were more excited about the knowledge than
knowledgable about the big bucks.  Short version:
Lilly asked one of the two (Crabtree, IIRC) to testify
against UW about their researchers' role in developing
the drug Xigris, and he realized that *he* had worked
on what led to it back in the '80's.  A
Lilly-affiliated scientist had since gotten some award
for the gene sequencing, without mentioning the work
of the 2 former NIHers...which rather po'd Crabtree. 
He's now suing Lilly.

Innovation is a collaboration of many, but I'd guess
that this refrain "it's ours alone" is significantly
overused by the big pharmas.

This site has a couple more articles on patent fights
involving Lilly:
http://news.moneycentral.msn.com/ticker/sigdev.asp?Symbol=LLY

This 2005 article mentions that a drug in question was
originally discovered by the Burnham Institute, and
later aquired by Integra LifeSciences:
http://www.signonsandiego.com/news/nation/20050420-1545-cnspatent.html

"...The peptides' role had been discovered earlier by
researchers at the Burnham Institute, which patented
the peptide sequence and ways to use it. Those patents
were subsequently acquired by Integra LifeSciences, a
New Jersey company.

After learning of the research at Scripps, Integra
asked Merck – which is unrelated to the U.S. drug
maker of the same name – to pay for a license for the
patents. When the two companies couldn't reach an
agreement, Integra sued for patent infringement..."

Research done at...as leading into potential drug
discovery:
http://www.drugresearcher.com/news/ng.asp?id=67074-poxvirus-vaccina-antivirals
"...Research done by an Imperial College London team
discovered the mechanism allowing Vaccinia virus to
shed its outer lipid membrane and enter cells.
Viruses, such as influenza, are surrounded by a single
lipid membrane, or envelope, and to enter cells this
membrane must be removed.  Previously, all enveloped
viruses were thought to shed their lipid membrane by
fusion with a cell membrane, which allows the virus
core to be released into the cell.

"This work has uncovered a completely novel biological
process. It increases our understanding of how viruses
can manipulate biological membranes and will help the
development of new drugs against poxviruses,”
commented professor Geoffrey Smith, from Imperial
College London...."

http://www.drugresearcher.com/news/ng.asp?id=67136-medulloblastoma-children-cancer
"...The new method is set to particularly benefit
children who often undergo chemotherapy that is
unpredictable and dangerous to the individual. The
technique aims to reduce this by locating specific
pathways in cancer that might be vulnerable to novel
therapies, speeding development of so-called
molecular-targeted therapies for a wide variety of
cancers.

Investigators at St. Jude Children's Research Hospital
believe that the ability to determine in individual
children which biochemical signalling pathway triggers
and sustains the cancer by identifying key genes that
are linked to that pathway.  The investigators proved
that this strategy is valid by demonstrating that it
is possible to assign children with medulloblastoma
into specific groups, depending on which biochemical
signalling pathway is abnormally active.

Based on this classification, novel drugs designed to
block a key protein in each specific pathway could be
correctly administered to the children most likely to
respond to them..."   

Here is one on an Isis Pharm's developing drug:
http://www.drugresearcher.com/news/ng.asp?id=59704-isis-develops-antisense
"The drug, ISIS 369645, is a second-generation
antisense inhibitor of the alpha subunit of the
interleukin 4 receptor, (IL4R-alpha)..."
(Who discovered the molecule is not stated; research
on interleukins has gone on in various institutes
around the world for years.)

One involving collaboration:
http://www.drugresearcher.com/news/ng.asp?id=59601-blueprint-tool-points
"25/04/2005  - A research program has released a small
molecule binding annotation and comparison tool, which
is expected to accelerate lead development in
antimicrobial drug discovery, as well as allow
chemists to develop safer, more specific herbicides
and pesticides with fewer side effects.  The Blueprint
Initiative has released the tool, which is a result of
data curated by the Protein Data Bank (PDB) and
genomic sequences in GenBank, is an extension of
Blueprint's Small Molecule Interaction Database
(SMID).

Blueprint's SMID-Genomes offer scientists a web-based
interface to browse 9.4 million predicted
small-molecule-protein binding interactions in an
organism-specific manner. To construct this tool,
Blueprint analysed NCBI's non-redundant sequence
database to identify potential binding sites based on
homology to known interactions using SMID-BLAST.

"Traditional chemical screening methods used by
pharmaceutical companies have focused on protein
targets, so scientists have had to test thousands of
compounds against each protein, often with little or
no forethought of likely candidates," said Dr Hogue.
"SMID-Genomes focuses on small molecules and scans
fully or partially sequenced genomes for potential
binding activity. The tool allows scientists to narrow
down the possibilities and focus on the most likely
candidates."

The SMID-Genomes interprets nearly 400,000 proteins
from more than 1500 completely sequenced bacterial,
eukaryotic of viral organisms. The database is one of
a number that is related to human health and disease
as it spans a long list of sequenced pathogenic
bacteria and infectious diseases.

"But as the number of genomes sequenced and the
catalogue of known protein-small molecule interactions
grows in the PDB repository, so too will the power of
the prediction tool," added Dr Hogue.

The SMID-Genome uniquely incorporates a feature that
allows scientists to simultaneously overlap the
small-molecule binding behaviours of up to five
organisms, permitting the direct comparison of
different genomes. 


This website has a lot of info and tons of articles,
BTW, which I will have to look at much more closely.

Anyway, my point is that the big pharmas depend on
various researchers and institutes for a fair amount
of "their" drug discoveries.

Debbi
It Takes A Team Maru

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