Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : HuMAB companies -- Ignore unavailable to you. Want to Upgrade?

To: Icebrg who wrote (532)	6/7/2003 10:43:55 AM
From: nigel bates	Respond to of 1022

So it's a race between the tobacco farmers and the microbreweries to get into the antibody business... Message 18886396 LEBANON, NEW HAMPSHIRE - Apr. 15, 2003 - GlycoFi, Inc. today announced the publication of a major scientific milestone in efforts to produce complex human glycoproteins in high capacity fungal production systems.... Use of combinatorial genetic libraries to humanize N-linked glycosylation in the yeast Pichia pastoris Byung-Kwon Choi, Piotr Bobrowicz, Robert C. Davidson, Stephen R. Hamilton, David H. Kung, Huijuan Li, Robert G. Miele, Juergen H. Nett, Stefan Wildt, and Tillman U. Gerngross Thayer School of Engineering, Dartmouth College, Hanover, NH 03755 Communicated by Phillips W. Robbins, Boston Medical Center, Boston, MA, March 4, 2003 (received for review December 5, 2002) The secretory pathway of Pichia pastoris was genetically re-engineered to perform sequential glycosylation reactions that mimic early processing of N-glycans in humans and other higher mammals. After eliminating nonhuman glycosylation by deleting the initiating -1,6-mannosyltransferase gene from P. pastoris, several combinatorial genetic libraries were constructed to localize active -1,2-mannosidase and human -1,2-N-acetylglucosaminyltransferase I (GnTI) in the secretory pathway. First, >32 N-terminal leader sequences of fungal type II membrane proteins were cloned to generate a leader library. Two additional libraries encoding catalytic domains of -1,2-mannosidases and GnTI from mammals, insects, amphibians, worms, and fungi were cloned to generate catalytic domain libraries. In-frame fusions of the respective leader and catalytic domain libraries resulted in several hundred chimeric fusions of fungal targeting domains and catalytic domains. Although the majority of strains transformed with the mannosidase/leader library displayed only modest in vivo [i.e., low levels of mannose (Man)5-(GlcNAc)2] activity, we were able to isolate several yeast strains that produce almost homogenous N-glycans of the (Man)5-(GlcNAc)2 type. Transformation of these strains with a UDP-GlcNAc transporter and screening of a GnTI leader fusion library allowed for the isolation of strains that produce GlcNAc-(Man)5-(GlcNAc)2 in high yield. Recombinant expression of a human reporter protein in these engineered strains led to the formation of a glycoprotein with GlcNAc-(Man)5-(GlcNAc)2 as the primary N-glycan. Here we report a yeast able to synthesize hybrid glycans in high yield and open the door for engineering yeast to perform complex human-like glycosylation. ------------------------------------------------------------------------ * Present address: GlycoFi, Inc., 21 Lafayette Street, Suite 200, Lebanon, NH 03766. To whom correspondence should be addressed at: Thayer School of Engineering, Dartmouth College, 8000 Cummings Hall, Hanover, NH 03755. E-mail: tillman.gerngross@dartmouth.edu. The member who communicated this paper is a Science Advisor for GlycoFi, Inc. www.pnas.org/cgi/doi/10.1073/pnas.0931263100

To: Icebrg who wrote (532)	6/7/2003 10:43:55 AM
From: nigel bates	Respond to of 1022

My money is on the microbreweries. Or it would be if I could buy some GlycoFi.

To: Icebrg who wrote (532)	6/9/2003 7:05:41 AM
From: Icebrg	Read Replies (1) \| Respond to of 1022

MedImmune and Micromet Sign Agreement to Co-Develop Treatment for B Cell Tumors Monday June 9, 6:03 am ET Partners Also Agree to Create Up To Six New Product Opportunities Based Upon Micromet's Novel Platform of Antibody Derivatives GAITHERSBURG, Md., and MUNICH, Germany, June 9 /PRNewswire-FirstCall/ -- MedImmune, Inc. (Nasdaq: MEDI - News) and Micromet AG (private) today announced an agreement to jointly develop Micromet's B cell tumor drug, MT103, the most- advanced representative of a novel class of antibody derivatives called Bi- Specific T Cell Engagers (BiTE(TM)). In addition, the parties agreed to create up to six novel drug candidates using Micromet's proprietary BiTE product platform. "This agreement with Micromet on MT103 and the promising BiTE platform reflects MedImmune's dedication to expanding its oncology pipeline," said James F. Young, Ph.D., MedImmune's president, research and development. "We are excited with the possibility of developing MT103 into a new treatment option for non-Hodgkin lymphoma and chronic lymphocytic leukemia. MT103 may also have application in autoimmune diseases, such as rheumatoid arthritis, myasthenia gravis, and systemic lupus erythematosus. We look forward to working with Micromet to create additional drug candidates using the BiTE technology." Micromet has initiated two European Phase 1 studies of MT103 in non- Hodgkin lymphoma (NHL) and plans to initiate a Phase 1 study in chronic lymphocytic leukemia (CLL) later this year. The BiTE compound MT103 directs and activates the patients' own T cells (a very potent type of killer cell) against tumor cells. MT103 targets a particular protein (the CD19 antigen), which is present on the large majority of B cells (white blood cells) but not on other types of blood cells or healthy tissues. MT103 may therefore be applied to the treatment of all B cell-related leukemias and lymphomas. The Leukemia & Lymphoma Society had estimated that approximately 53,900 Americans would be diagnosed with NHL in 2002, with approximately 7,000 new cases of CLL each year. Under the terms of the agreement, Micromet will receive milestone payments based on the successful development, filing, registration and marketing of MT103, as well as royalties on MedImmune's North American sales of the product. Furthermore, MedImmune Ventures, Inc., a wholly owned venture capital subsidiary of MedImmune, will make an investment in Micromet. MedImmune receives Micromet's product rights to MT103 in North America and will assume responsibility for clinical development, registration and commercialization of the product in that region. As part of the agreement, MedImmune will develop the commercial manufacturing process and supply clinical trial material as well as commercial products for all markets. Micromet retains rights to MT103 outside of North America. In addition to the MT103 co-development agreement, the parties will collaborate to create and develop up to six new products based on the BiTE platform. Micromet is entitled to receive milestones and royalties on future product sales of all resulting BiTE products. In addition, Micromet has the option to obtain exclusive European rights for BiTE compounds based on targets non-proprietary to MedImmune and the option to receive co-promotion rights in Europe for BiTE compounds based on MedImmune's proprietary targets. For each new BiTE molecule MedImmune will cover full development costs up to Phase 1. Micromet will be responsible for the generation of the new BiTE molecules. The parties expect to initiate the first joint BiTE program within the next six months. Erich Felber, MD, chief executive officer of Micromet, said, "We are pleased to establish a co-development relationship with MedImmune, one of the world's leading biotechnology companies. MedImmune's track record in building product franchises and its commitment to the oncology and antibody arena make them an ideal partner. The partnership not only strengthens our clinical-stage portfolio, but also creates and funds additional opportunities with the BiTE product platform." Notes to editors BiTE(TM) (Bispecific T cell Engagers) Visit micromet.de to download a backgrounder on BiTE(TM) technology. micromet.de

To: Icebrg who wrote (532)	6/10/2003 11:16:14 AM
From: tuck	Respond to of 1022

Here's the abstract: >>Published online before print June 10, 2003 Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0832472100 Plant Biology Function and glycosylation of plant-derived antiviral monoclonal antibody Kisung Ko , Yoram Tekoah , Pauline M. Rudd , David J. Harvey , Raymond A. Dwek , Sergei Spitsin , Cathleen A. Hanlon , Charles Rupprecht , Bernhard Dietzschold , Maxim Golovkin , and Hilary Koprowski * *Biotechnology Foundation Laboratories at Thomas Jefferson University, 1020 Locust Street, JAH, Philadelphia, PA 19107; Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom; and Rabies Section, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30333 Contributed by Hilary Koprowski, April 24, 2003 Plant genetic engineering led to the production of plant-derived mAb (mAbP), which provides a safe and economically feasible alternative to the current methods of antibody production in animal systems. In this study, the heavy and light chains of human anti-rabies mAb were expressed and assembled in planta under the control of two strong constitutive promoters. An alfalfa mosaic virus untranslated leader sequence and Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum retention signal were linked at the N and C terminus of the heavy chain, respectively. mAbP was as effective at neutralizing the activity of the rabies virus as the mammalian-derived antibody (mAbM) or human rabies Ig (HRIG). The mAbP contained mainly oligomannose type N-glycans (90%) and had no potentially antigenic (1,3)-linked fucose residues. mAbP had a shorter half-life than mAbM. The mAbP was as efficient as HRIG for post-exposure prophylaxis against rabies virus in hamsters, indicating that differences in N-glycosylation do not affect the efficacy of the antibody in this model.<< Wonder if this will awaken interest in the area sufficient to make LSBC's IP and expertise worth enough to allow it to survive. Cheers, Tuck

To: Icebrg who wrote (532)	6/10/2003 11:16:14 AM
From: tuck	Respond to of 1022

Here's the abstract: >>Published online before print June 10, 2003 Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0832472100 Plant Biology Function and glycosylation of plant-derived antiviral monoclonal antibody Kisung Ko , Yoram Tekoah , Pauline M. Rudd , David J. Harvey , Raymond A. Dwek , Sergei Spitsin , Cathleen A. Hanlon , Charles Rupprecht , Bernhard Dietzschold , Maxim Golovkin , and Hilary Koprowski * *Biotechnology Foundation Laboratories at Thomas Jefferson University, 1020 Locust Street, JAH, Philadelphia, PA 19107; Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom; and Rabies Section, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30333 Contributed by Hilary Koprowski, April 24, 2003 Plant genetic engineering led to the production of plant-derived mAb (mAbP), which provides a safe and economically feasible alternative to the current methods of antibody production in animal systems. In this study, the heavy and light chains of human anti-rabies mAb were expressed and assembled in planta under the control of two strong constitutive promoters. An alfalfa mosaic virus untranslated leader sequence and Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum retention signal were linked at the N and C terminus of the heavy chain, respectively. mAbP was as effective at neutralizing the activity of the rabies virus as the mammalian-derived antibody (mAbM) or human rabies Ig (HRIG). The mAbP contained mainly oligomannose type N-glycans (90%) and had no potentially antigenic (1,3)-linked fucose residues. mAbP had a shorter half-life than mAbM. The mAbP was as efficient as HRIG for post-exposure prophylaxis against rabies virus in hamsters, indicating that differences in N-glycosylation do not affect the efficacy of the antibody in this model.<< Wonder if this will awaken interest in the area sufficient to make LSBC's IP and expertise worth enough to allow it to survive. Epicyte is also in this area Cheers, Tuck

To: Icebrg who wrote (532)	6/12/2003 12:25:59 AM
From: scaram(o)uche	Read Replies (2) \| Respond to of 1022

>> said Jeffrey Price, chairman of Planet Biotechnology in Hayward, Calif. << Ugh. Price was CEO of NTII, during the days when they let memantine sit and rot. There may be some choice comments at the beginning of the NTII thread?? Tobacco....... the first seven claims of the Epicyte patent........ 1. A transgenic plant, comprising: (a) plant cells containing nucleotide sequences encoding immunoglobulin heavy- and light-chain polypeptides, wherein each polypeptide contains a leader sequence forming a secretion signal; and (b) immunoglobulin molecules encoded by said nucleotide sequences, wherein said leader sequence is cleaved from said immunoglobulin molecules following proteolytic processing. 2. The plant of claim 1 wherein at least one of the leader sequences is a heterologous leader sequence. 3. The plant of claim 1 wherein the nucleotide sequences encode a mammalian immunoglobulin. 4. The plant of claim 1 wherein the immunoglobulin is an immunoglobulin superfamily molecule. 5. The plant of claim 1 which is a dicotyledonous plant. 6. The plant of claim 1 which is a monocotyledonous plant. 7. The plant of claim 1, which is a tobacco plant. (69 total claims) Perhaps there is some point of contention, where Planet or LSBC or ????????? believe they can sneak through?