Production of Therapeutic Glycoproteins - Patent and Technology Report -Key players, innovators and Industry Analysis

Executive Summary

The majority of clinically approved protein drugs bear some form of post-translational modification, most commonly glycosylation. Glycosylation is the attachment of a carbohydrate group to a protein, catalyzed by enzymes called glycosyl transferases. It is either N-linked, in which a carbohydrate is attached to the side chain of a specific asparagine, or O-linked, in which it is attached to the hydroxyl oxygen of a serine or threonine, the former being most prominent. While N-linked glycosylation occurs largely in the endoplasmic reticulum (ER) of mammalian cells, O-linked glycosylation initiates in either the ER or Golgi apparatus.

Glycosylation is important because it can influence the therapeutic efficacy, immunogenicity, solubility, and in-vivo half life of the glycoprotein. A major obstacle in the pharmaceutical application of glycoproteins is the inherent heterogeneity of their glycan structures. Mammalian cell culture systems, especially Chinese hamster ovary (CHO) cells, are the preferred method for the production of therapeutic glycoproteins. Other systems such as E.coli, filamentous fungi, yeast, insects, plants and transgenic animals are also being engineered to produce proteins with optimal glycosylation pattern. Optimizing production methods to obtain a glycoform profile as similar to that in humans is the current goal in glycoengineering research. Some of the bestsellers among therapeutic proteins will soon lose patent protection. Therefore, a market for off-patent biotherapeutics is expected to open up, which is worth billions of dollars. Biosimilars or follow-on biologics of the original glycoprotein drugs has led to the marketing of 'copies' of these drugs, varying in glycosylation patterns, etc., and are a challenge for pharmaceutical companies as well as regulating authorities.

Dolcera report focuses on finding the key innovators and the industry ecosystem through relevant patents, clinical trials and university data encompassing the advances in the manufacture of therapeutic glycoproteins. The relevant keywords used in the search were obtained after an extensive study of relevant scientific articles and patents. Additional keywords were further obtained by searching for the MeSH terms of the relevant keywords. The relevant class codes for the search were obtained from the control patents and keyword based searches coupled with manual search of classification index. Dolcera has retrieved over 800 relevant patents related to manufacture of therapeutic glycoproteins, covering over 47 worldwide patenting authorities. The report highlights year-wise patent activity (trend line) along with the key industrial players in the field. Patents were categorized on the basis of patent focus- whether novel or modified cell lines or hosts, transgenic animals, novel enzymes, chemical/cell free methods of synthesis, and novel fermentation methods or culture conditions. The categorized patents were further analyzed to determine the key players under each category. A comprehensible result in the form of Dolcera dashboard has been given. Dashboard links the Companies in each category to their patents, hence making an interactive platform for analysis. Furthermore, patents have been mapped to commercially available products produced by the respective assignees and other licensees.