Historically, gelatin is denatured collagen and is typically isolated from bovine or porcine skin or bone by acid or base extraction. Approximately fifty thousand metric tons of gelatins are produced annually for medical use. Most of this volume is consumed in some aspect of oral drug delivery, which uses mixtures of bovine and porcine gelatin. Additionally, thousands of metric tons are used annually for parenteral formulations and devices.

Currently available gelatin preparations consist of a distribution of polypeptide fragments of different sizes, different isoelectric points (pI), and different gelling properties, and often exhibit lot-to-lot variability. Furthermore the physiochemical properties of these gelatins vary depending on method of extraction, amount of thermal denaturation employed, and electrolyte content of the resulting material.

The variable nature of such gelatin preparations, therefore, presents a significant challenge to those who use these protein mixtures in the manufacture of other products. Gelatin hydrolysates represent a specialized preparation for use in situations where gel formation is not desired, such as in the stabilization of vaccines and biologics or in other liquid formulations. Extracted from animal sources, this type of gelatin requires additional processing steps such as thermal hydrolysis or treatment with a protease.

Using recombinant technology, FibroGen can produce gelling or non-gelling gelatins. FibroGen's recombinant gelatins are highly purified, fully characterized, genetically distinct molecules that can replace hydrolyzed animal gelatin and other excipients currently used in a variety of pharmaceutical applications including the formulation of vaccines and biological drugs, resuscitation fluids and the manufacturing of gel capsules and tablets.

As fully synthetic molecules, FibroGen's recombinant gelatins eliminate many of the variables and drawbacks associated with tissue-derived material. This technology allows the production of gelatins with defined molecular weights, pI, guaranteed lot-to-lot reproducibility, and the ability to tailor the molecule to match a specific application.

Advantages of fully synthetic gelatins:

• Multifunctional. FibroGen produces a variety of recombinant gelatin molecules using a recombinant yeast system (Pichia pastoris) to express specified fragments of Type I, alpha1 human sequence collagen. The resulting recombinant gelatin molecules have defined molecular weights and pI that confer specific performance characteristics to match the need in a variety of pharmaceutical applications.

• Customizability. Using recombinant technology, FibroGen can design and express gelatin molecules with predetermined characteristics. Our technology not only advances the quality and reproducibility of gelatin preparations but creates flexibility.

• Lot-to-lot consistency. FibroGen's gelatin products are fully characterized, homogenous preparations of defined molecular weight and physio-chemical properties not previously available from animal sources. This means that each lot can be reproduced in a consistent manner with 99% purity.

• Safety. FibroGen's recombinant gelatin production system does not contain human or animal components, thereby eliminating the risk of contamination with disease causing pathogens, such as viruses and prions that cause mad cow disease and its human variant Creutzfeldt-Jakob Disease associated with use of animal- and plasma-derived materials.

• Biocompatibility. The risk of eliciting an immune response is also reduced with FibroGen's recombinant gelatin molecules that are based on human sequences of collagen Type I alpha1 chains.

FibroGen has produced a series of recombinant fragments by cloning and expressing defined segments of the human alpha1 (I) procollagen gene. Each bar in the diagram represents a different recombinant gelatin fragment and relative location of the fragment within the helical domain of the human alpha1 (I) chain; similarly colored bars share the same N-terminal sequence. The numbers within each bar represent the number of amino acids in the fragment.

FibroGen's recombinant gelatin molecules analyzed by SDS-PAGE. Each band represents a single molecular weight species of recombinant gelatin secreted into conditioned media by Pichia pastoris strains expressing various collagen fragments. The numbers above each band represent the number of amino acids in the fragment. The left lane shows molecular weight standards (kd) for comparison.