Whether you are a large or small innovator, CMO or biogenerics company and seek to develop new licensing/income streams, dream of starting a new company or simply are looking for a good investment, there are ample opportunities to get involved now, particularly before the advantages of getting involved in earlier stages of technology development and licensing are lost.

Currently, there are just a few major players promoting new technologies, and as shown in this directory, there are an incredible number of technological advances ready for adoption, adaptation and further development, providing ample opportunities for process improvements and profit.

Already, most major large (bio)pharmaceutical companies have made some moves in this area, with some paying millions dollars to acquire companies whose only or primary assets are new manufacturing platforms, while others are quietly but actively investigating, optioning, licensing-in and implementing new technologies.

For example, for about $400 million Merck & Co. acquired GlyoFi, a developer of methods for manufacture of antibodies with human-like and modifiable glycosylation using the yeast Pichia pastoris; and for $56.5 million, Hoffmann-La Roche acquired Therapeutic Human Polyclonals Inc., a developer of methods for manufacture of polyclonal humanized antibodies in transgenic rabbits.

The opportunities for profit are also illustrated by past technology licensing, e.g., Columbia University took in nearly $370 million over 17 years (average over $20 million/year) from licensing of co-transformation technology (see related entry) at less than a 1% royalty; Stanford University and the University of California each took in over $200 million from licensing of the Cohen-Boyer patents covering basic aspects of recombinant protein manufacture.

This directory was designed to provide you with access to the most important new technologies relevant to the commercial-scale manufacture of biopharmaceutical products, particularly recombinant proteins, including glycoproteins and antibodies. If you have not recently fully assessed your commitment to your current systems (quite possibly the same basic technologies you and others are familiar with, e.g., used in graduate school or since entering the industry; the same ones in use for decades), you probably should. If you are not considering implementing totally systems/platforms or at least improving the one(s) you currently use, you are missing significant opportunities. New systems and improvements to traditional ones offer compelling increases in product yields and associated reductions in manufacturing costs.

This is the 1st edition of Biopharmaceutical Expression Systems and Genetic Engineering Technologies: Current and Future Manufacturing Platforms. Expression systems encompass the technologies – biological materials and associated know-how – needed to genetically modify organisms for the manufacture of recombinant proteins (including glycoproteins and antibodies).

This book is designed to be the single most informative source concerning commercial biopharmaceutical product manufacturing-related expression systems and basic engineering technologies, with emphasis on those currently used for biopharmaceutical manufacture and those available for commercial licensing for this purpose; providing basic information for the knowledgeable user to determine relevance for their applications; conduct further research and/or contact technology licensing sources. The primary goal is to inform the user of the many technologies in commercial use and those claimed to be useful for commercial-scale manufacture of biopharmaceutical products, rather than provide detailed or comparative information about each.

This directory should save you considerable time and effort in finding technologies relevant to your interests. It should reliably cover relevant technologies currently being used commercially, those being actively offered for licensing, those discussed in industry news sources and review articles, and those offered by leading genetic engineering and bioprocessing technology licensors.

Simply stated, coverage concentrates on host cells/organisms, basic genetic engineering methods, recombinant constructs and the many technologies available to enable or improve expression of desired proteins, including glycoproteins and antibodies. This directory concentrates on the core genetic materials (e.g., host cell lines and organisms) and related methods and materials, e.g., vectors, promoters, selection and amplification methods, chaperones, etc., used or claimed useful for commercial-scale manufacture of biopharmaceutical products, primarily recombinant proteins and monoclonal antibodies. Thus, this directory concentrates only on what is used or needed for upstream manufacture.

This directory includes broad platform technologies, generally defined by the living host cells/organisms being used, which may be natural or genetically modified to begin with; and the basic genetic engineering technologies needed to get the desired gene sequence(s) into these hosts and get these genes efficiently expressed (transcribed and translated) for commercial-scale manufacture. Thus, this directory includes a number of specific genetic engineering technologies, e.g., vectors, promoters, chaperones, affinity fusion protein purification schemes, etc., useful with all, some or specific platform technologies/host systems.

Technologies involve or can be defined or viewed in many ways or on many different levels. In nearly all cases, technologies have been described in or exemplified by patents. Technologies involve know-how or enabling knowledge and related information. With biopharmaceutical manufacturing and genetic engineering technologies, this invariably involves information, e.g., methods and gene/protein sequences, often embodied in genetic constructs and culture collection deposits. In the biopharmaceutical area, just about every technology of interest has been or is in the process of being patented; and most technology acquisition or other technology transfer involves patent licensing. In many cases, all one needs to effectively acquire rights and implement a desired technology is to license related patents. In many other cases technology acquisition/licensing should involve or requires initial or even continuing technical assistance from the inventors or the organization handling licensing.

Coverage includes both technologies currently in predominant use for biopharmaceutical product manufacture, with these primarily based on use of E. coli, Chinese hamster ovary (CHO) cells and yeasts, primarily Saccharomyces cerevisiae, and new and upcoming alternative platforms/hosts, most of which have not yet been adopted/adapted for commercial-scale manufacture. Much of the older technologies, particularly those in use since the 1980s (including most E. coli, CHO and yeast technologies), have in recent years either lost or will soon lose patent protection. Many users of this directory will likely be interested in these proven, regulatory agency-familiar, cheap (now or soon no licensing expenses involved) but, in many respects, inefficient technologies. Most, if not most, directory users are presumed to be interested in new alternatives and/or significantly improving current in-house platform technologies, e.g., by adopting newer technologies offering higher yields.

If a technology does not involve genetic materials and their manipulation, generally host cells/organisms and genetic constructs or methods, it has not been included, no matter how relevant to biopharmaceutical manufacture. Thus, this directory does not include:

1. technologies relevant to specific products, e.g., product-specific gene/protein sequences; only technologies relevant to manufacture of all or broad classes of proteins, including glycoproteins and antibodies.
2. protein engineering or other molecule design technologies, unless substantially involving commercial scale protein expression. Thus, nearly all methods for designing and predicting protein structures are not included.
3. protein screening technologies, including selecting for desired active agent/product characteristics. An incredible number and diversity of screening technologies are available, but are not included.
4. some rather generic genetic engineering, molecular biologic laboratory technologies, with these sometimes discussed in brief generic entries.
5. generic, non-genetic engineering-based methods for host cell/organism modification, e.g., nontargeted or random mutation-based methods; e.g., exposure to mutagens and selection for desired characteristics or adaptation to specific; e.g., protein-free, culture media by growth, repeated passages and selection of adapting cells/organisms.
6. microorganism and cell culture, culture media, fermentation, and related bioreactor and fermenter technologies. This directory does include various microbes, other organisms and plant, insect and animal cell lines, many adapted to specific types of culture or bioreactors, e.g., adherent or suspension culture, and/or adapted to specific types of culture media, e.g., serum- or protein-free media; but does not include technologies related to bioreactors, fermentors, bioreactor/fermentor control, etc.
7. downstream technologies, including purification. This directory does not include separation, purification, formulation, viral inactivation or other downstream technologies. This directory does include genetic and protein expression-based methods for downstream processing, particularly purification using fusion proteins for affinity-based purification, but does not include chromatography and other technologies for protein purification.

Descriptive entries are provided for ~340 technologies. Data fields are:

1. Title – The various names of associated with technologies and major components are included, optionally followed by a hyphen and the author’s annotation of the host/organism system(s) used and/or special capabilities of the technology (e.g., glycosylation; antibodies manufacture).
2. Organizations involved – The major organizations involved are listed along with characterization of their role or involvement in the technology, e.g,. licensor, patent assignee, research, etc.
   
   
3. Description – A summary of available information about the technology concentrating on functionality, improvements provided, etc.
4. Use with – Brief characterization of the main host cells/organisms used with the technology.
5. Use to make – A brief characterization of the types of products the technology is designed or claimed to be useful for.
   
   
6. Background – An optional field presenting claimed benefits or desirable characteristics of the technology.
7. Patents – Information about relevant patents.
8. Licensing information – Information about licensing contact(s), optionally with information about related commercial activities, e.g., know licensees.
9. Products made with this tech – An optional field presenting information about biopharmaceutical products made using/incorporating the technology.
10. Further info – An optional field usually presenting citations to related publications.

The monographs are divided into two main sections:

1. The first section presents broadly-enabling, platform-type technologies, particularly novel host cells and organisms.
2. The second section presents more specific, supporting and component technologies. These may be broadly generic, applying to diverse hosts/platforms, or applying to multiple or just one major host/ platform.

Within each of the two main technology sections, monographs are loosely classified or grouped by broad platform technologies, generally host cell/organism classes, e.g., E. coli, yeasts, mammalian cells, etc. However, keep in mind that most technologies are or can be presumed to either be relevant to multiple broad platforms, as is often presented in monographs, or may actually be relevant to just one specific platform, e.g., vectors claimed useful with yeasts may actually be only or primarily useful with S. cerevisiae or another yeast (but available information does not make this clear).

The following indexes are provided:

1. Company/Organization
2. Subject
3. Primary Host Systems