Loading patent…
AssigneeAltus Biologics Inc.
InventorsAlexey L. Margolin, Rose A. Persichetti, Nancy L. St. Clair, Nazer K. Khalaf
Estimating the term…
Protein crystals crosslinked with a multifunctional crosslinking agent are produced that have the ability to change from an insoluble and stable form to a soluble and active form and to release protein activity at a controlled rate when a change in environment surrounding the crystals occurs. The change in environment may be a change in temperature, pH, chemical composition or shear force acting on the crystals, or a change from a concentrate to a dilute form, or a combination of the changes. The crosslinked protein crystals have a half-life activity under storage conditions greater than at least 2 times that of the soluble protein that is crystallized to form the crystals that are crosslinked, and under conditions of use have an activity similar to the soluble protein. Crosslinking is carried out by reacting a slurry of protein crystals with a multifunctional crosslinking agent such as glutaraldehyde, glyoxal, octanedialdehyde or succinaldehyde using a concentration of crosslinking agent and time for crosslinking that provides crosslinked protein crystals having the desired ability to change due to a change in environment. An epoxide multifunctional crosslinking agent may be used in combination with glutaraldehyde for crosslinking. The crosslinked protein crystals can be used for protein delivery, and may be used in cleaning agents such as detergents, pharmaceutical compositions, vaccines, personal care compositions, veterinary compositions, foods, feeds, diagnostics and decontamination formulations. Proteins used include enzymes and therapeutic or prophylactic proteins such as hormones and antibodies.
A method for producing crosslinked protein crystals crosslinked with a multifunctional crosslinking agent, comprising the step of reacting a slurry of protein crystals with a multifunctional crosslinking agent, under conditions sufficient to induce crosslinking of said crystals to the extent that the resulting crosslinked crystals are characterized by the ability to change from insoluble and stable form to soluble and active form upon a change in their environment, said change being selected from the group consisting of change in temperature, change in pH, change in chemical composition, change from concentrate to dilute form, change in shear force acting upon the crystals and combinations thereof;
A method for producing crosslinked protein crystals crosslinked with a multifunctional crosslinking agent, comprising the step of reacting a slurry of protein crystals with a multifunctional crosslinking agent, under conditions sufficient to induce crosslinking of said crystals to the extent that the resulting crosslinked crystals are characterized by a half-life of activity under storage conditions which is greater than at least 2 times that of the soluble form of the protein that is crystallized to form said crystals that are crosslinked, and by an activity similar to that of the soluble form of the protein under conditions of use;
A method for producing crosslinked protein crystals crosslinked with a multifunctional crosslinking agent, comprising the step of reacting a slurry of protein crystals with a multifunctional crosslinking agent, under conditions sufficient to induce crosslinking of said crystals to the extent that the resulting crosslinked crystals are characterized by being capable of releasing their protein activity at a controlled rate upon exposure to a change in their environment, said change being selected from the group consisting of change in pH, change in soluble concentration, change in temperature, change in chemical composition, change in shear force acting upon the crystals and combinations thereof;
A method for producing crosslinked protein crystals crosslinked with a multifunctional crosslinking agent, comprising the step of reacting a slurry of protein crystals with a multifunctional crosslinking agent, under conditions sufficient to induce crosslinking of said crystals to the extent that the resulting crosslinked crystals are characterized by the ability to change from insoluble and stable form to soluble and active form upon a change in their environment, said change being selected from the group consisting of change in temperature, change in pH, change in chemical composition, change from concentrate to dilute form, change in shear force acting upon the crystals and combinations thereof;
A method for producing crosslinked protein crystals crosslinked with a multifunctional crosslinking agent, comprising the step of reacting a slurry of protein crystals with a multifunctional crosslinking agent, under conditions sufficient to induce crosslinking of said crystals to the extent that the resulting crosslinked crystals are characterized by a half-life of activity under storage conditions which is greater than at least 2 times that of the soluble form of the protein that is crystallized to form said crystals that are crosslinked, and by an activity similar to that of the soluble form of the protein under conditions of use;
A method for producing crosslinked protein crystals crosslinked with a multifunctional crosslinking agent, comprising the step of reacting a slurry of protein crystals with a multifunctional crosslinking agent, under conditions sufficient to induce crosslinking of said crystals to the extent that the resulting crosslinked crystals are characterized by being capable of releasing their protein activity at a controlled rate upon exposure to a change in their environment, said change being selected from the group consisting of change in pH, change in soluble concentration, change in temperature, change in chemical composition, change in shear force acting upon the crystals and combinations thereof;
A method for producing crosslinked protein crystals crosslinked with a multifunctional crosslinking agent, comprising the step of reacting a slurry of protein crystals with a multifunctional crosslinking agent, under conditions sufficient to induce crosslinking of said crystals to the extent that the resulting crosslinked crystals are characterized by the ability to change from insoluble and stable form to soluble and active form upon a change in their environment, said change being selected from the group consisting of change in temperature, change in pH, change in chemical composition, change from concentrate to dilute form, change in shear force acting upon the crystals and combinations thereof;
A method for producing crosslinked protein crystals crosslinked with a multifunctional crosslinking agent, comprising the step of reacting a slurry of protein crystals with a multifunctional crosslinking agent, under conditions sufficient to induce crosslinking of said crystals to the extent that the resulting crosslinked crystals are characterized by a half-life of activity under storage conditions which is greater than at least 2 times that of the soluble form of the protein that is crystallized to form said crystals that are crosslinked, and by an activity similar to that of the soluble form of the protein under conditions of use;
A method for producing crosslinked protein crystals crosslinked with a multifunctional crosslinking agent, comprising the step of reacting a slurry of protein crystals with a multifunctional crosslinking agent, under conditions sufficient to induce crosslinking of said crystals to the extent that the resulting crosslinked crystals are characterized by being capable of releasing their protein activity at a controlled rate upon exposure to a change in their environment, said change being selected from the group consisting of change in pH, change in soluble concentration, change in temperature, change in chemical composition, change in shear force acting upon the crystals and combinations thereof;
A method for producing crosslinked protein crystals crosslinked with a multifunctional crosslinking agent, comprising the step of reacting a slurry of protein crystals with a multifunctional crosslinking agent, under conditions sufficient to induce crosslinking of said crystals to the extent that the resulting crosslinked crystals are characterized by the ability to change from insoluble and stable form to soluble and active form upon a change in their environment, said change being selected from the group consisting of change in temperature, change in pH, change in chemical composition, change from concentrate to dilute form, change in shear force acting upon the crystals and combinations thereof;
A method for producing crosslinked protein crystals crosslinked with a multifunctional crosslinking agent, comprising the step of reacting a slurry of protein crystals with a multifunctional crosslinking agent, under conditions sufficient to induce crosslinking of said crystals to the extent that the resulting crosslinked crystals are characterized by a half-life of activity under storage conditions which is greater than at least 2 times that of the soluble form of the protein that is crystallized to form said crystals that are crosslinked, and by an activity similar to that of the soluble form of the protein under conditions of use;
A method for producing crosslinked protein crystals crosslinked with a multifunctional crosslinking agent, comprising the step of reacting a slurry of protein crystals with a multifunctional crosslinking agent, under conditions sufficient to induce crosslinking of said crystals to the extent that the resulting crosslinked crystals are characterized by being capable of releasing their protein activity at a controlled rate upon exposure to a change in their environment, said change being selected from the group consisting of change in pH, change in soluble concentration, change in temperature, change in chemical composition, change in shear force acting upon the crystals and combinations thereof;
A method for producing crosslinked protein crystals crosslinked with a multifunctional crosslinking agent, comprising the step of reacting a slurry of protein crystals with a first multifunctional crosslinking agent and at least a second multifunctional crosslinking agent, under conditions sufficient to induce crosslinking of said crystals to the extent that the resulting crosslinked crystals are characterized by the ability to change from insoluble and stable form to soluble and active form upon a change in their environment, said change being selected from the group consisting of change in temperature, change in pH, change in chemical composition, change from concentrate to dilute form, change in shear force acting upon the crystals and combinations thereof;
A method for producing crosslinked protein crystals crosslinked with a multifunctional crosslinking agent, comprising the step of reacting a slurry of protein crystals with a first multifunctional crosslinking agent and at least a second multifunctional crosslinking agent, under conditions sufficient to induce crosslinking of said crystals to the extent that the resulting crosslinked crystals are characterized by a half-life of activity under storage conditions which is greater than at least 2 times that of the soluble form of the protein that is crystallized to form said crystals that are crosslinked, and by an activity similar to that of the soluble form of the protein under conditions of use;
A method for producing crosslinked protein crystals crosslinked with a multifunctional crosslinking agent, comprising the step of reacting a slurry of protein crystals with a first multifunctional crosslinking agent and at least a second multifunctional crosslinking agent, under conditions sufficient to induce crosslinking of said crystals to the extent that the resulting crosslinked crystals are characterized by being capable of releasing their protein activity at a controlled rate upon exposure to a change in their environment, said change being selected from the group consisting of change in pH, change in soluble concentration, change in temperature, change in chemical composition, change in shear force acting upon the crystals and combinations thereof;
Dependencies are inferred from the claim text.