Recombinant Human Albumin-Human Granulocyte Colony Stimulating Factor For The Prevention Of Neutropenia

• US 20100227818A1
• Filed: 01/15/2010
• Published: 09/09/2010
• Est. Priority Date: 01/16/2009
• Status: Abandoned Application

• Current Assignee: Teva Pharmaceutical Industries Limited
• Original Assignee: Teva Biopharmaceuticals USA, Inc. (Teva Pharmaceutical Industries Limited)
• Inventors: Bell, Adam Carr, Herpst, Jeffrey, Bock, Jason Benjamin
• Application Number:
  US12/688,754
• Publication Number:
  US 20100227818A1
• Time in Patent Office: Days
• US Class Current: 424/85.100
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 38/38 Albumins
• CPC Class Codes: A61K 38/385 Serum albumin
• CPC Class Codes: A61K 47/643 Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid

Abstract

Disclosed are compositions and methods for treating, preventing and ameliorating conditions and diseases characterized by a lowered white blood cell count. The methods and compositions described herein include a fusion polypeptide formed from human serum albumin protein (“HSA”) and human granulocyte-colony stimulating factor (“G-CSF”).

Claims

1. A method of treating or preventing neutropenia in a human subject comprising administering to a human subject exhibiting neutropenia or at risk of developing neutropenia, recombinant human albumin-human granulocyte colony stimulating factor in an amount effective to treat the subject.

3. The method according to claim 1 wherein the human subject is suffering from a non-myeloid malignancy and is receiving at least one myelosuppressive anti-cancer drug associated with a clinically significant incidence of febrile neutropenia.

5. The method of claim 1, wherein:

(a) grade 4 neutropenia in the subject is eliminated;

(b) grade 4 neutropenia in the subject is reduced;

(c) the duration of severe neutropenia is reduced in the subject;

(d) the duration of grade 4 neutropenia in the subject is less than 5 days;

(e) the duration of grade 3 neutropenia in the subject is eliminated;

(f) the duration of grade 3 neutropenia in the subject is decreased;

or

(g) any combination thereof.

6. The method of claim 1, wherein administering recombinant human albumin-human granulocyte colony stimulating factor induces a rise in white blood cells (WBC).

7. The method according to claim 1, wherein:

(a) the number of neutrophils is increased in the subject;

(b) a decrease in the number of neutrophils is inhibited in the subject;

(c) the nadir absolute neutrophil count (ANC) is increased in the subject;

(d) the recovery ANC is increased in the subject;

(e) the time to ANC recovery is reduced in the subject;

or

(f) any combination thereof.

8. The method according to claim 1, wherein the amount of recombinant human albumin-human granulocyte colony stimulating factor administered to the subject is selected from the group consisting of:

(a) from about 50 μ

g/kg to about 450 μ

g/kg;

(b) about 50 μ

g/kg;

(c) about 150 μ

g/kg;

(d) about 300 μ

g/kg;

(e) about 450 μ

g/kg;

(f) from about 30 mg to about 60 mg;

(g) about 30 mg;

(h) about 40 mg;

(i) about 50 mg;

(j) about 60 mg;

or

(k) any combination thereof.

9. The method of claim 1, wherein neutropenia is selected from the group consisting of primary neutropenia, acute neutropenia, severe chronic neutropenia (SCN), severe congenital neutropenia (Kostmann'"'"'s syndrome), severe infantile genetic agranulocytosis, benign neutropenia, cyclic neutropenia, chronic idiopathic neutropenia, secondary neutropenia, syndrome associated neutropenia, and immune-mediated neutropenia.

10. The method of claim 1 wherein neutropenia is caused or associated with radiation, alcoholism, drugs, allergic disorders, aplastic anemia, autoimmune disease, T-γ

lymphoproliferative disease (T-γ

LPD), myelodysplasia, myelofibrosis, dysgammaglobulinemia, paroxysmal nocturnal hemoglobinuria, cancer, vitamin B₁₂ deficiency, folate deficiency, viral infection, bacterial infection, spleen disorder, hemodialysis, or transplantation, leukemia, myeloma, lymphoma, metastatic solid tumors which infiltrate and replace the bone marrow, toxins, bone marrow failure, Schwachman-Diamond syndrome, cartilage-hair hypoplasia, dyskeratosis congenita, glycogen storage disease type IB, splenomegaly of any cause, intrinsic defects in myeloid cells or their precursors.

11. The method of claim 3, wherein recombinant human albumin-human granulocyte colony stimulating factor is administered at a time selected from the group consisting of:

(a) at least 12 hours after administration of the myelosuppressive anti-cancer drug;

(b) at least 18 hours after administration of the myelosuppressive anti-cancer drug;

(c) at least 24 hours after administration of the myelosuppressive anti-cancer drug.

12. The method of claim 11 wherein administering recombinant human albumin-human granulocyte colony stimulating factor prior to the myelosuppressive anti-cancer drug induces a rise in WBC.

13. The method of claim 11 wherein administering recombinant human albumin-human granulocyte colony stimulating factor prior to chemotherapy induces a rise in ANC.

14. The method of claim 3 wherein the non-myeloid malignancy comprises breast cancer.

15. The method of claim 3 wherein the myelosuppressive anticancer drugs comprise doxorubicin and docetaxel.

16. The method of claim 15 wherein about 50 mg/m² doxorubicin and about 75 mg/m² docetaxel are administered sequentially by intravenous infusion on the same day for at least one treatment cycle.

17. The method of claim 15 wherein about 60 mg/m² doxorubicin and about 75 mg/m² docetaxel are administered sequentially by intravenous infusion on the same day for at least one treatment cycle.

18. The method of claim 3, wherein ANC and WBC return to normal at a time period selected from the group consisting of:

(a) by day 10 after chemotherapy;

(b) by day 11 after chemotherapy;

(c) by day 12 after chemotherapy;

(d) by day 13 after chemotherapy;

(e) by day 14 after chemotherapy;

or

(f) by day 15 after chemotherapy.

19. The method of claim 3, wherein on day 14 after chemotherapy administration the rise in ANC in patients treated with recombinant human albumin-human granulocyte colony stimulating factor is lower than the rise in ANC in patients treated with an equivalent dose of pegfilgrastim.

20. The method according to claim 1 wherein administering recombinant human albumin-human granulocyte colony stimulating factor induces a rise in lymphocytes, monocytes, eosinophils, basophils, or any combination thereof.

21. The method according to claim 1 wherein the number of lymphocytes, monocytes, eosinophils, basophils or any combination thereof is increased in the subject.

22. The method according to claim 1, wherein a decrease in the number of lymphocytes, monocytes, eosinophils, or basophils is inhibited in the subject.

2. A method of treating or preventing leukopenia in a human subject comprising administering to a human subject exhibiting leukopenia or at risk of developing leukopenia, recombinant human albumin-human granulocyte colony stimulating factor in an amount effective to treat the subject.

4. A method of decreasing the incidence of infection, as manifested by febrile neutropenia, in a human subject with non-myeloid malignancies and receiving at least one myelosuppressive anti-cancer drug associated with a clinically significant incidence of febrile neutropenia, comprising administering to the subject recombinant human albumin-human granulocyte colony stimulating factor in an amount effective to treat the subject.