Pharmaceutical Compositions Containing sc(Fv)2
AssigneeChugai Seiyaku Kabushiki Kaisha
InventorTomoyuki Igawa
Life of this patent
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Abstract
The present inventor discovered stabilizing agents/stabilizing conditions for suppressing isomerization reactions of sc(Fv)2. It was also discovered that the above-mentioned isomerization reactions can be suppressed through use of freeze-dried formulations. As disclosed herein, by applying the discovered stabilizing agents/stabilizing conditions or the freeze-dried formulation, the isomerization reaction of an sc(Fv)2-type molecule from the bivalent scFv type to the single chain diabody type, and/or the isomerization reaction from a single chain diabody type to a bivalent scFv type can be suppressed in both directions or one direction.
Claims43
A pharmaceutical composition comprising an sc(Fv)2, to which at least one substance selected from the group consisting of salt, amino sugar, sugar alcohol, amino acid, and pH adjusting agent has been added.
A pharmaceutical composition comprising an sc(Fv)2, wherein the pH is 4.5 to 9.0.
A pharmaceutical composition comprising an sc(Fv)2, wherein the pH is 6.0 to 9.0.
A pharmaceutical composition comprising an sc(Fv)2, wherein the salt concentration is 50 mM to 1000 mM.
A pharmaceutical composition comprising an sc(Fv)2, wherein the dosage form is a freeze-dried formulation.
A method for producing a pharmaceutical composition comprising an sc(Fv)2, wherein the method comprises the steps of:
- (i) preparing an sc(Fv)2 composition;
- and
- (ii) suppressing an isomerization reaction of the prepared sc(Fv)2 composition.
A method for producing a pharmaceutical composition comprising sc(Fv)2, wherein the method comprises the steps of:
- (i) preparing an sc(Fv)2 composition;
- and
- (ii) adding at least one substance selected from the group consisting of salt, amino sugar, sugar alcohol, amino acid, and pH adjusting agent to the prepared sc(Fv)2 composition.
A method for producing a pharmaceutical composition comprising an sc(Fv)2, wherein the method comprises the steps of:
- (i) preparing an sc(Fv)2 composition;
- and
- (ii) adjusting the pH of the prepared sc(Fv)2 composition to pH 4.5 to 9.0.
A method for producing a pharmaceutical composition comprising an sc(Fv)2, wherein the method comprises the steps of:
- (i) preparing an sc(Fv)2 composition;
- and
- (ii) adjusting the pH of the prepared sc(Fv)2 composition to pH6.0 to 9.0.
A method for producing a pharmaceutical composition comprising an sc(Fv)2, wherein the method comprises the steps of:
- (i) preparing an sc(Fv)2 composition;
- and
- (ii) adjusting the salt concentration of the prepared sc(Fv)2 composition to 50 mM to 1000 mM.
A method for producing a pharmaceutical composition comprising an sc(Fv)2, wherein the method comprises the steps of:
- (a) producing an sc(Fv)2 composition in which the content ratio of the single chain diabody type is higher than the content ratio of the bivalent scFv type by incubating the sc(Fv)2 composition at 15° C. to 50° C., and/or pH3.0 to 6.0, and/or salt concentration of 500 mM or less;
- (b) obtaining the produced single chain diabody-type sc(Fv)2;
- and
- (c) stabilizing the single chain diabody-type sc(Fv)2 composition obtained in step (b).
A method for producing a pharmaceutical composition comprising an sc(Fv)2, wherein the method comprises the steps of:
- (a) producing an sc(Fv)2 composition in which the content ratio of the bivalent scFv type is higher than the content ratio of the single chain diabody type by incubating the sc(Fv)2 composition at 15° C. to 50° C., and/or pH3.0 to 6.0, and/or salt concentration of 500 mM or less;
- (b) obtaining the produced bivalent scFv-type sc(Fv)2;
- and
- (c) stabilizing the bivalent scFv-type sc(Fv)2 composition obtained in step (b).
A method for producing a pharmaceutical composition comprising an sc(Fv)2, wherein the method comprises the steps of:
- (i) preparing an sc(Fv)2 composition;
- and
- (ii) freeze-drying the prepared sc(Fv)2 composition.
A method for suppressing the isomerization of an active ingredient in a pharmaceutical composition, wherein the method comprises the step of adding at least one substance selected from the group consisting of salt, amino sugar, sugar alcohol, amino acid, and pH adjusting agent.
A method for suppressing the isomerization of an active ingredient in a pharmaceutical composition, wherein the method comprises the step of setting the pH to pH4.5 to 9.0.
A method for suppressing the isomerization of an active ingredient in a pharmaceutical composition, wherein the method comprises the step of setting the pH to pH6.0 to 9.0.
A method for suppressing the isomerization of an active ingredient in a pharmaceutical composition, wherein the method comprises the step of setting the salt concentration to 50 mM to 1000 mM.
A method for suppressing the isomerization of an active ingredient in a pharmaceutical composition, wherein the method comprises the step of freeze-drying.
A stabilizing agent used for suppressing the isomerization reaction of an sc(Fv)2, wherein the stabilizing agent comprises at least on substance selected from the group consisting of salt, amino sugar, sugar alcohol, amino acid, and pH adjusting agent.
A method of screening for a substance that suppresses the isomerization reaction of an sc(Fv)2, wherein the method comprises the steps of:
- (i) preparing an sc(Fv)2 composition;
- (ii) contacting a test substance with the prepared sc(Fv)2 composition;
- (iii) measuring the presence of suppression of an isomerization reaction of an sc(Fv)2 in the sc(Fv)2 composition contacted with the test substance;
- and
- (iv) selecting the substance that suppresses the isomerization reaction of the sc(Fv)2.
Dependencies are inferred from the claim text.