Drug – bio-affecting and body treating compositions – Conjugate or complex of monoclonal or polyclonal antibody,... – Conjugated to proteinaceous toxin or fragment thereof
Reexamination Certificate
1998-01-27
2002-04-16
Scheiner, Laurie (Department: 1648)
Drug, bio-affecting and body treating compositions
Conjugate or complex of monoclonal or polyclonal antibody,...
Conjugated to proteinaceous toxin or fragment thereof
C424S154100, C424S178100, C530S388750, C530S391700, C530S370000
Reexamination Certificate
active
06372217
ABSTRACT:
BACKGROUND OF THE INVENTION
Acute lymphoblastic leukemia (ALL) is the most common form of childhood malignancy. Champlin et al.,
Blood
, 73, 2051 (1989). Each year about 1250 children less than 15 years of age are found to have acute lymphoblastic leukemia. Champlin et al., cited supra. Recently, dramatic improvements in the multiagent chemotherapy of children with ALL have resulted in cure rates of 70-75%. Poplack et al.,
Pediatric Clinics of North America
, 35, 903 (1988). However, despite these recent improvements, as many as 1 in 5 patients will eventually suffer leukemic relapse. Riehm et al.,
Haematol. Blood Transf
., 33, 439 (1990). This occurrence of relapsed patients equates to 250 cases/year and is equivalent to the number of newly diagnosed cases of childhood acute nonlymphoblastic leukemia, medulloblastoma, and rhabdomyosarcoma. Furthermore, this relapse rate surpasses the number of newly diagnosed cases of childhood Ewings sarcoma, osteogenic sarcoma, hepatoma, and germ cell tumors. The unsatisfactory outcome of this population makes a significant contribution to overall pediatric cancer mortality, despite the excellent outcome for the substantial majority of children with ALL.
Currently, the major challenge in the treatment of childhood ALL is to cure patients who have relapsed despite intensive multiagent chemotherapy. Champlin et al., cited supra. For patients who have relapsed while on therapy or shortly after elective cessation of therapy, the overall survival is very poor. Poplack et al., cited supra. Treatment of these relapsed children has generally employed either intensive chemotherapy to achieve a second remission, subsequent use of either nonablative chemotherapy or ablative radiochemotherapy and bone marrow transplantation (BMT). Kersey et al.,
N. Engl. J. Med
., 117,461 (1987). However, recurrence of leukemia is the major obstacle to the success of either approach. Dicke et al.,
Clin. Hematol
., 15, 86 (1986).
Furthermore, treatment of these relapsed patients by the intensification of cytotoxic therapy using conventional drugs will likely cause overlapping toxicities and may result in delays which may erode the intensity of therapy. Consequently, the development of new potent anti-ALL drugs and the design of combinative treatment protocols utilizing these new agents, have emerged as focal points for research in the therapy of relapsed ALL.
Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and the second most frequent leukemia in children, accounting for 20-25% of acute childhood leukemias. Priesier et al.,
Blood
, 80, 2600 (1992). Though the majority of patients with myeloid leukemias initially respond to intensive chemotherapy regimens, most will relapse and eventually succumb to their disease. Additionally, attempts to identify useful and specific prognostic factors to effectively stratify good and poor outcome AML patients have generally not been successful, with the result that all patients receive very intensive therapy at the price of great morbidity. Furthermore, contemporary multiagent chemotherapy regimens for AML fail to cure more than half of the patients because of multidrug resistance of leukemia cells and often lead to potentially fatal systemic toxicity. Gale et al.,
Sem. Hematol
., 24, 40 (1987).
Finally, although allogeneic bone marrow transplantation has been demonstrated to be an effective therapy for many patients with myeloid leukemia, its application is limited by the availability of suitable HLA-matched and MLC-unreactive donors. Woods et al.,
J. Clin. Oncol
., 11, 1448 (1993). In autologous bone marrow transplantation for childhood AML, gene marker studies have indicated that subclinical disease in unpurged “remission” marrow harvested for transplantation contributes significantly to disease recurrence. Brenner et al.,
Lancet
, 341, 85 (1993). Myeloablative chemotherapy or supralethal radiochemotherapy followed by allogeneic or autologous bone marrow transplantation are associated with considerable morbidity and mortality and fail to substantially improve the overall survival of AML patients, underscoring the need for rational, drug design-based therapies for AML. Yeaper et al.,
New Engl. J. Med
., 315, 141 (1986); Woods et al., cited supra.
Another disease of the immune system is acquired immunodeficiency syndrome (AIDS). Infection with the human immunodeficiency virus type I (HIV-1) constitutes a worldwide public health problem. Venkatesan,
Science
, 241, 1481 (1988). The critical basis for the immunopathogenesis of HIV infection is the depletion of the CD4+ helper/inducer subset of T-cells, resulting in profound immunosuppression. See Dahlgleish et al,
Nature
, 312, 763 (1984); Fauci,
Clin Res
., 32, 491 (1985); Ho et al.,
N. Engl. J. Med
., 317, 278 (1987). HIV has a selective tropism for CD4+ T-cells and macrophages which is mediated by interaction of its envelope (env) protein gp120 with an essential component of the cell surface receptor for HIV-1, the CD4 antigen. Lasky et al.,
Science
, 233, 209 (1986). After HIV binds to the first domain of the CD4 molecule via the external envelope glycoprotein gp120, the virus is internalized and uncoated. Fauci,
Science
, 29, 617 (1988). Once uncoated, the viral genomic RNA is transcribed to DNA by the enzyme reverse transcriptase. The proviral DNA is then integrated into the host chromosomal DNA. After integration of the provirus, the infection may assume a latent phase or the proviral DNA may transcribe viral genomic RNA and messenger RNA. Protein synthesis, processing, and virus assembly occur with budding of the mature virion from the cell surface.
At present, AIDS is incurable and treatment modalities that reduce HIV-1 replication in vivo by using reverse transcriptase inhibitors such as zidovudine/ZDV (formerly termed azidothymidine/AZT) and dideoxyinosine (ddl) cause substantial side effects. Yarchoan et al.,
Blood
, 78, 859 (1991). Although ZDV delays the disease progression in HIV-1 seropositive asymptomatic individuals and has improved the survival of patients with AIDS and AIDS-related complex (ARC), the therapeutic response is frequently transient. Volberding et al.,
N. Engl. J. Med
., 322, 941 (1990); Fischl et al.,
Ann. Intern. Med
., 112, 727 (1990); Fischl et al.,
N. Engl. J. Med
., 317, 185 (1987). Moreover, variants of HIV-1 that are resistant to ZDV emerge to thwart the success of continued therapy. Erice et al.,
Clinical Infectious Diseases
, 18, 149 (1994). Recent data indicate that resistance among HIV-1 isolates also emerges during dideoxyinosine (ddI) therapy. St. Clair et al.,
Science
, 253, 1557 (1991). These characteristics confirm the resilience of HIV-1 and the need for more powerful strategies against this virus.
Drug targeting is a potentially attractive new approach to killing malignant or HIV-infected cells, an approach which can leave normal or uninfected tissue or cells unharmed. A decisive breakthrough in drug targeting was the advent of hybridoma technology, making many monoclonal antibodies (MoAbs) available in essentially limitless supply. To construct therapeutic reagents with selectivity for certain populations of cells, MoAbs or other cell targeting proteins are linked to bioactive moieties to form biotherapeutic agents referred to as immunoconjugates, immunotoxins or fusion proteins, which can combine the selectivity of the targeting moiety with the potency of the bioactive moiety. The choice of MoAb (or other targeting moiety) is based on the surface antigen profile of a target cell.
For the past decade, these types of biotherapeutic agents have been under investigation for the treatment of various cancers. Although these biotherapeutic agents have shown some potential to provide safe and effective therapy for human disease, many difficulties remain. Ideally, consistently locatable and reliable markers on target cells would permit the binding portion of biotherapeutic agents to completely avoid non-target tissue. In reality, cross-reactivity with antigens expressed by vital
Parkin Jeffrey S.
Regents of the University of Minnesota
Scheiner Laurie
Schwegman Lundberg Woessner & Kluth P.A.
LandOfFree
Methods for the treatment of CD7+ viral infection with... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods for the treatment of CD7+ viral infection with..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods for the treatment of CD7+ viral infection with... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2926435