United States Patent:   6,019,968

Assignee:  Inhale Therapeutic Systems, Inc. (San Carlos, CA)

Filed:  October 16, 1997

This invention relates to dispersible antibody compositions and methods for preparing and using these compositions. In particular, the present invention relates to dry powder dispersible antibody compositions wherein antibody conformation is preserved. The compositions have good powder dispersibility and other desirable characteristics for pulmonary delivery of therapeutic antibodies.

SUMMARY OF THE INVENTION

The present invention provides dispersible dry powder antibody compositions and methods for their preparation and use. These dispersible dry powder antibody compositions have a moisture content of less than about 10% by weight (% w) water, usually about 1-5% by weight, and preferably less that about 3% by weight of water. They have a particle size of about 0.1 to 7 .mu.m mass median diameter (MMD), usually about 0.4 to 5 .mu.m MMD, preferably about 1 to 4 .mu.m and most preferably about 1-3 .mu.m MMD. The dispersible dry powder antibody compositions of the present invention result in a delivered dose of greater than about 30%, usually greater than about 40%, preferably greater than about 50% and most preferably greater than about 60%. They have an aerosol particle size distribution of about 1-5 .mu.m mass median aerodynamic diameter (MMAD), usually about 1.5-4.5 .mu.m MMAD and preferably about 1.5-4.0 .mu.m MMAD, or with at least about 40% (preferably at least about 50%) of the particles less than about 3.3 .mu.m in diameter. The compositions contain at least about 40% by weight antibody. Further, the antibodies in these compositions are not aggregated and are present in their native conformation so as to retain their biological activity.

According to the present invention, antibody containing compositions having improved characteristics which overcome at least some of the deficiencies noted above with respect to prior compositions are provided. The present invention provides compositions and methods which provide a predetermined concentration of antibody, and, optionally, other excipients as a dry dispersible powder. The antibody is optionally formulated prior to spray drying with compatible excipients such as sugars, buffers, salts, surfactants, polymers, other proteins and other specific stabilizing additives as needed to provide a therapeutically effective dose, inhibit degradation during drying, promote powder dispersibility and achieve acceptable physical and chemical stability of the powder at room temperature while maintaining antibody integrity.

In one aspect the invention provides dry powder compositions for pulmonary delivery comprising an antibody that is substantially in its native conformation. Such compositions retain antibody activity upon reconstitution.

In another aspect the invention provides antibody-based dry powder compositions which are spray dried from the antibody and, optionally, excipient, in a solvent under conditions to provide a respirable dry powder. Solvents for such mixtures may include water and ethanol.

In a yet further aspect, the invention provides methods for preventing or treating a condition by administering the dry powder antibody compositions described above.

Claim 1 of 13 Claims

1. An IgG antibody-based dry powder composition for pulmonary delivery comprising a predetermined amount of IgG antibody which is non-aggregated and is in its native conformation in respirable dry powder particles having a particle size less than 10 micrometers wherein said composition has a delivered dose efficiency of at least about 30%.

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