Hyaluronidase Enzyme Formulations for High Volume Administration
In one aspect, the present disclosure provides a formulation comprising a hyaluronidase enzyme and a therapeutically effective amount of an active ingredient. In another aspect, the present disclosure provides a method of administering a high volume of the formulation in a single administration to treat a disease or disorder in a subject.
1 .- 74 . (canceled)
75 . A method of subcutaneous administration of a hyaluronidase PH20 enzyme formulation to a subject in need thereof,
the method comprising subcutaneously administering to the subject about 3 mL to about 50 mL of a formulation comprising recombinant human hyaluronidase PH20 enzyme comprising a sequence having at least 95% amino acid sequence identity to an amino acid sequence selected from any of SEQ ID NO: 1 through 7 and SEQ ID NO: 15, and having an activity of about 500 U/mL to about 5,000 U/mL,
wherein the subcutaneous administration occurs at a rate of about 0.10 mL/sec to about 1.0 mL/sec.
76 . The method of claim 75 , wherein the formulation further comprises an active ingredient selected from a small molecule, a peptide, a nanoparticle, an antibody, and an antibody fragment.
77 . The method of claim 75 , comprising administering to the subject about 10 mL to about 20 mL of the formulation or about 3 mL to about 15 mL of the formulation.
78 . The method of claim 75 , wherein the subcutaneous administration occurs with one or more of i) to iv):
i) a starting delivery force of about 3 lbf to about 50 lbf,
ii) an ending delivery force of about 5 lbf to about 20 lbf.;
iii) a starting pressure of about 50 psi to about 200 psi; and
iv) an ending pressure of about 20 psi to about 75 psi.
79 . The method of claim 75 , wherein the subcutaneous administration occurs via a high volume autoinjector.
80 . The method of claim 79 , wherein the high volume autoinjector comprises a prefilled syringe containing the formulation.
81 . The method of claim 80 , wherein the prefilled syringe comprises a needle having a gauge of about 20 to about 33.
82 . The method of claim 79 , wherein the subcutaneous administration occurs via the high volume autoinjector using a compressed-gas cylinder as an energy source.
83 . The method of claim 75 , wherein the formulation has a viscosity of about 1 cP to about 50 cP.
84 . The method of claim 75 , wherein the recombinant human hyaluronidase PH20 enzyme comprises an amino acid sequence of SEQ ID NO: 2.
85 . A method of reducing one or more side effects of a high-volume subcutaneous injection in a subject in need thereof,
the method comprising subcutaneously administering to the subject about 3 mL to about 50 mL of a formulation comprising recombinant human hyaluronidase PH20 enzyme comprising a sequence having at least 95% amino acid sequence identity to an amino acid sequence selected from any of SEQ ID NO: 1 through 7 and SEQ ID NO: 15, and having an activity of about 500 U/mL to about 5,000 U/mL,
wherein the subcutaneous administration occurs at a rate of about 0.10 mL/sec to about 1.0 mL/sec and the one or more side effects are selected from pain and discomfort at the injection site, back leakage at the injection site, swelling volume at the injection site, swelling height at the injection site, bleb swelling size, bleb induration, and bleb resolution time.
86 . The method of claim 85 , wherein the formulation further comprises an active ingredient selected from a small molecule, a peptide, a nanoparticle, an antibody, and an antibody fragment.
87 . The method of claim 85 , comprising administering to the subject about 10 mL to about 20 mL of the formulation or about 3 mL to about 15 mL of the formulation.
88 . The method of claim 85 , wherein the subcutaneous administration occurs with one or more of i) to iv):
i) a starting delivery force of about 3 lbf to about 50 lbf,
ii) an ending delivery force of about 5 lbf to about 20 lbf.;
iii) a starting pressure of about 50 psi to about 200 psi; and
iv) an ending pressure of about 20 psi to about 75 psi.
89 . The method of claim 85 , wherein the subcutaneous administration occurs via a high volume autoinjector.
90 . The method of claim 89 , wherein the high volume autoinjector comprises a prefilled syringe containing the formulation.
91 . The method of claim 90 , wherein the prefilled syringe comprises a needle having a gauge of about 20 to about 33.
92 . The method of claim 89 , wherein the subcutaneous administration occurs via the high volume autoinjector using a compressed-gas cylinder as an energy source.
93 . The method of claim 85 , wherein the formulation has a viscosity of about 1 cP to about 50 cP.
94 . The method of claim 85 , wherein the recombinant human hyaluronidase PH20 enzyme comprises an amino acid sequence of SEQ ID NO: 2.