Intellectual Property
The following US and International patent applications are available for sale:

Enhanced Purification of Antibodies and Antibody Fragments by Apatite Chromatography

Enhanced Purification of Phosphorylated and Non-phosphorylated Biomolecules by Apatite Chromtography

If you are interested in acquiring either body of technology,
please contact Pete Gagnon.

Enhanced Purification of Antibodies and Antibody Fragments by Apatite Chromatography

US Patent Application No. 200901875, filed January 16, 2009, published July 23, 2009.

Summary
This technology involves purification of antibodies on calcium derivatized hydroxyapatite (Ca-HA) and fluorapatite (CA-FA). In the presence of soluble calcium and the absence of soluble phosphate, calcium forms stable complexes with apatite phosphate sites, converting them into secondary calcium sites, essentially creating a high density calcium metal affinity support with unique selectivity. Exposure to phosphate strips the calcium, making selective elution impossible. However, compounds with weaker calcium affinity, particularly sulfate, allows selective elution without stripping the calcium, thereby producing novel selectivities that cannot be obtained with native apatites. Selective elution can also be accomplished with borate and lactate. Presently known or anticipated applications include:

Enhanced purification of Fab. Fab does not bind to Ca-HA. Fc-containing contaminants and most other proteins do. This supports >95% purity in a single step. For more information see Gagnon, P., Cheung, C-W., Yazaki, P., 2009, Reverse Calcium Affinity Purification of Fab with Calcium Derivatized Hydroxyapatite, Journal of Immunological Methods, 342 115-118 (2009)

Enhanced removal of antibody aggregates. Elution of IgG monoclonal antibodies from native hydroxypatite with borate or lactate enhances aggregate separation over what can be obtained with phosphate gradients or halide gradients in the presence of phosphate. Elution of monoclonal IgM from native hydroxypatite with sulfate enhances aggregate separation over what can be obtained with phosphate gradients or halide gradients in the presence of phosphate. Phosphate-free Buffer Systems: A New Frontier for Apatite Chromatography, 4th International Conference on Hydroxypatite, Sonoma, CA May 5-7, 2008

Enhanced antibody binding capacity. The use of Ca-HA increases the binding capacity of IgG by up to a factor of 4 at a conductivity value of about 2 mS/cm. IgG binding capacity on Ca-HA in the presence of 0.8 M sodium chloride is still nearly twice as high as native HA at low conductivity, and more than 10 times higher than native HA at 0.8 M sodium chloride. See Phosphate-free Buffer Systems: A New Frontier for Apatite Chromatography, 4th International Conference on Hydroxypatite, Sonoma, CA May 5-7, 2008

Solid phase unfolding and re-folding of antibodies. IgG remain bounds to Ca-HA even in the peresence of 6M guanidine-HCl, making it possible to unfold aggregates, then refold IgG to its native configuration by gradual removal of guanidine, potentially through intermediate refolding formulations such as 0.6 M arginine. The refolded proteins can be eluted either directly from CA-HA, or by conversion of Ca-HA to native HA with subsequent elution by phosphate gradients or other elution methods.

Enhanced DNA, endotoxin, and virus clearance. DNA does not elute from Ca-HA in non-phosphate buffers. Endotoxin follows the same trends as DNA. These results suggest that clearance of lipid enveloped virus from proteins eluted from Ca-HA should be similarly enhanced.

Enhanced Purification of Phosphorylated and Non-phosphorylated Biomolecules by Apatite Chromtography

US Patent Application No. 200901875, filed January 16, 2009, published July 23, 2009.

Summary
The basic technology for this application is the same as above but for non-antibody applications. Presently known or anticipated applications include:

Enhanced capacity and purification of phosphoproteins. Elution of native HA with sulfate increases the separation of phosphorylated proteins from non-phosphorylated proteins. Binding of phosphorylated proteins is preferentially enhanced on Ca-HA, and their fractionation from non-phosphoyrylated proteins enhanced even more than sufate gradients on native HA. These methods can be used for analytical or preparative applications.

Enhanced capacity and purification of DNA. Elution of Ca-HA with sulfate, borate, or lactate supports removal of most protein contamaminants. Ca-HA can be subsequently converted to native HA by exposure to 10 mM phosphate, and the DNA eluted selectively in a phosphate gradient.

Enhanced capacity and purification of virus. Elution of Ca-HA with sulfate, borate, or lactate supports removal of most protein contamaminants. Ca-HA can be subsequently converted to native HA by expeosure to 10 mM phosphate, and virus eluted selectively in a phosphate gradient.

Solid phase unfolding and re-folding of proteins. Proteins remain bound to Ca-HA even in the peresence of 6M guanidine-HCl, making it possible to unfold aggregates, then refold protein to their native configuration by gradual removal of guanidine. The refolded proteins can be eluted either directly from CA-HA, or by conversion of Ca-HA to native HA with subsequent elution by phosphate gradients or other elution methods. This approach also supports the use of other chaotropes such as urea. A modification of this approach should support direct adsorption onto CA-HA of unfolded proteins from inclusion bodies, even in concentrated guanidine solutions.

Unique selectivies for protein fractionation. Elution of Ca-HA with sulfate, borate, or lactate supports unique selectivities for protein fractionation.