- Dock and Lock (DNL) Method has Broad Spectrum of Potential Applications -
MORRIS PLAINS, N.J., April 25 /PRNewswire-FirstCall/ -- Immunomedics,
Inc. (Nasdaq: IMMU), a biopharmaceutical company focused on developing
monoclonal antibodies, and its wholly owned subsidiary, IBC
Pharmaceuticals, Inc., today announced the development of a novel platform
technology that can be used to generate multifunctional agents for diverse
applications. The on-line article entitled "Stably tethered multifunctional
structures of defined composition made by the dock and lock method for use
in cancer targeting," and authored by E.A. Rossi, D.M. Goldenberg, T.M.
Cardillo, W.J. McBride, R.M. Sharkey and C.H. Chang, can be accessed at
http://www.pnas.org/papbyrecent.shtml. The print issue will be published in
the Proceedings of the National Academy of Sciences of the USA (PNAS) on
May 2, 2006.
This new technology may enable the creation of virtually any
multifunctional protein for diverse applications. For example, one
potential application is to connect multiple antibody fragments with toxic
drugs or radioisotopes for disease therapy or imaging. Another possibility
is to increase the circulation time of hormones, hematopoietic growth
factors, or cytokines in the body by linking them to polymers or albumin.
The method could also provide a novel means for selective targeting in gene
therapy.
Termed the Dock and Lock (DNL) method, the technology is based on the
exploitation of two alpha-helical peptides that are found in nature to bind
specifically with each other. By recombinantly fusing or chemically
attaching each peptide to a constituent of interest, these helices provide
an excellent linker module for "docking" the two modified components into a
quasi-stable structure, which is further "locked" into a stable complex.
"The DNL method can be applied to conjugate, quantitatively and
site-specifically, various proteins or non-proteins into stably tethered
complexes that retain the full functionalities of the individual components
and are suitable for both in vitro and in vivo applications," commented Dr.
Chien-Hsing Chang, Executive Vice President of Research at IBC
Pharmaceuticals. "A unique feature of the DNL method is that in its
simplest format one of the two components is always provided with two
copies, which can be very important for increased therapeutic efficacy.
Suitable components for this technology include antibody fragments, peptide
haptens, polyethylene glycols, human serum albumin, cytokines, DNA
vaccines, small interfering RNAs, enzymes, fluorescent proteins and a
variety of scaffold-based binding proteins," he added.
To prove the validity of the technology, a new trivalent, bispecific
protein, TF2, comprising three stably linked Fab fragments, was generated
from two of Immunomedics' humanized antibodies, hMN-14, which binds
specifically to carcinoembryonic antigen (CEA), and h679, which recognizes
the peptide-hapten, histamine-succinyl-glycine (HSG).
By means of a 'pretargeting' method pioneered by IBC Pharmaceuticals, a
bispecific antibody or fusion protein, derived from hMN-14 and h679, is
first injected to target to the tumor, followed by giving an HSG-carrying
radiotracer that binds selectively to the second arm of the bispecific
antibody at the tumor site. Pretargeting studies reported in this PNAS
article using TF2 and a technetium-99m-labeled HSG-radiotracer in a
CEA-expressing human colon cancer growing in mice demonstrated that 30% of
injected radiotracer was bound to tumor within one hour. As a result of the
rapid tumor uptake, exceptional tumor-to-nontumor ratios were achieved. At
0.5, 1, and 24 hours after the administration of the radiotracer, the
tumor-to-blood ratios were 13, 66, and 395, respectively. These data
demonstrate that TF2 is highly stable and capable of in vivo applications.
More importantly, other constructs made by the DNL method are also expected
to be stable in vivo with retained biological properties.
"We believe the DNL method is superior, in at least five major aspects,
to existing technologies that involve the conjugation of two or more
biological entities: (1) The technology provides a convenient and facile
way of constructing different proteins and non-proteins from modular
subunits on demand; (2) the new method has shown good productivity of pure
products with defined composition; (3) the resulting conjugates show high
stability in vivo; (4) the multifunctional complexes produced can
potentially have higher activity than each of their individual components;
and (5) the technology generates potentially non-immunogenic molecules use
as therapeutics," commented Cynthia L. Sullivan, President and Chief
Executive Officer of Immunomedics. "This exciting new technology is another
testimony of our core strength in research and development. We continue to
build on our strong track record of creating new and innovative products
from our laboratories," further commented Ms. Sullivan.
About the Dock and Lock (DNL) Method
The DNL method is a platform technology that utilizes the natural
interaction between two proteins, cyclic AMP-dependent protein kinase (PKA)
and A-kinase anchoring proteins (AKAPs). The region that is involved in
such interaction for PKA is called the dimerization and docking domain
(DDD), which always appears in pairs. Its binding partner in AKAPs is the
anchoring domain (AD). When mixed together, DDD and AD will bind with each
other spontaneously to form a binary complex, a process termed docking.
Once "docked," certain amino acid residues incorporated into DDD and AD
will react with each other to "lock" them into a stably tethered structure.
The outcome of the DNL method is the exclusive generation of a stable
complex, in a quantitative manner that retains the full biological
activities of its individual components. Diverse proteins, peptides, and
nucleic acids are among suitable components that can be linked to either
DDD or AD. Since DDD always appears in pairs, any component that is linked
to DDD will have two copies present in the final products.
About IBC Pharmaceuticals
IBC is a development-stage biopharmaceutical company focused on the
development and commercialization of proprietary pretargeting agents for
the detection and treatment of various cancers and other serious diseases.
These products are based on IBC's patented technology platform referred to
as the "Affinity Enhancement System," or AES. The Company currently has
several product candidates in pre-clinical and clinical development, and is
extending its pretargeting technology to include bispecific antibodies made
by the "dock and lock" method.
About Immunomedics
Immunomedics is a New Jersey-based biopharmaceutical company focused on
the development of monoclonal, antibody-based products for the targeted
treatment of cancer, autoimmune and other serious diseases. We have
developed a number of advanced proprietary technologies that allow us to
create humanized antibodies that can be used either alone in unlabeled or
"naked" form, or conjugated with radioactive isotopes, chemotherapeutics or
toxins, in each case to create highly targeted agents. Using these
technologies, we have built a pipeline of therapeutic product candidates
that utilize several different mechanisms of action. Our lead product
candidate, epratuzumab, is currently in two pivotal Phase III trials for
the treatment of patients with moderate and severe lupus (ALLEVIATE A and
B). At present, there is no cure for lupus and no new lupus drug has been
approved in the U.S. in the last 40 years. We believe that our portfolio of
intellectual property, which includes approximately 90 patents issued in
the United States, and more than 250 other issued patents worldwide,
protects our product candidates and technologies. Visit our web site at
http://www.immunomedics.com.
This release, in addition to historical information, may contain
forward-looking statements made pursuant to the Private Securities
Litigation Reform Act of 1995. Such statements, including statements
regarding clinical trials, out-licensing arrangements, and capital raising
activities, involve significant risks and uncertainties and actual results
could differ materially from those expressed or implied herein. Factors
that could cause such differences include, but are not limited to, risks
associated with new product development (including clinical trials outcome
and regulatory requirements/actions), competitive risks to marketed
products and availability of required financing and other sources of funds
on acceptable terms, if at all, as well as the risks discussed in the
Company's filings with the Securities and Exchange Commission. The Company
is not under any obligation, and the Company expressly disclaims any
obligation, to update or alter any forward-looking statements, whether as a
result of new information, future events or otherwise.
For More Information:
Immunomedics Inc.
Dr. Chau Cheng
Associate Director
Investor Relations & Business Analysis
(973) 605-8200, extension 123
ccheng@immunomedics.com
SOURCE Immunomedics, Inc.
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Related links:
http://www.Immunomedics.com
http://www.prnewswire.com/comp/113121.html /
CONTACT:
Dr. Chau Cheng, Associate Director, Investor
Relations & Business Analysis, of Immunomedics Inc.,
+1-973-605-8200, extension 123, ccheng@immunomedics.com
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