Drug – bio-affecting and body treating compositions – Solid synthetic organic polymer as designated organic active... – Aftertreated polymer
Reexamination Certificate
2001-12-07
2004-10-19
Smith, Lynette R. F. (Department: 1645)
Drug, bio-affecting and body treating compositions
Solid synthetic organic polymer as designated organic active...
Aftertreated polymer
C424S078080, C424S078180, C424S078170, C424S167100, C424S489000, C424S499000, C424S501000, C424S085100, C424S085200, C424S811000, C424S451000, C424S439000, C424S442000, C424S457000, C514S458000, C514S055000, C514S057000, C514S002600
Reexamination Certificate
active
06805857
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Technical Field
This invention is related to emergency medical preparedness against anthrax bio-terrorism. More particularly, the present invention details a treatment and therapy for anthrax that sharply reduces the risk of mortality with “Zero” tolerance for time.
2. Description of Related Art
In a typical patient with inhalation anthrax, the onset of illness begins with flu-like symptoms and may include fever, malaise, cough and chest discomfort. However, unlike the flu, patients with inhalation anthrax rapidly progress downhill with acute symptoms of respiratory distress and tightening in the chest with constricting sensations. Fever, septic shock and death may soon follow within a span of 3-5 days. According to the consensus document published on anthrax bio-terrorism in 1999, the strategic release of anthrax spores in a large metropolitan city could cause the death of 130,000 to 3 million people. The medical cost is estimated to be 26.2 billion dollars per 100,000 cases, (Novello, A. C. “Dear Doctor letter with 6 attachments” Oct. 19, 2001). This worst-case scenario is due to the high (80-90%) mortality from the inhalation form of anthrax even with state of the art medical care.
In anthrax bio-terrorism, the major cause of concern is the risk of high mortality in the evolving medical war scenario at an international level, it is practically impossible to predict the magnitude and scale of bio-terrorist's operation. It is also not possible to predict where and when anthrax will strike. Urgently, therefore, there is a need for life saving technology that can be deployed globally in real time to reduce the immediate risk of mass murders by a bio-terrorist. Such a technology will be life saving both for the military and civilian defenses and would result in saving billions of dollars for the government. Current industry standard estimates for new drug development is 10-15 years at a cost of over $500 million. Anthrax illness in natural settings is rare. In its bio-terrorism form, its magnitude of problems and timing of attacks are unpredictable. Under this scenario, the current efforts to develop bio-defense industry with a proposed cost estimate of $50 billion doesn't address the critical needs of country's defense in real time. (Hensley, S. and Winslow, R. “Drug Companies Contemplate New Role as Biodefense Contractors” Wall Street Journal, Nov. 12, 2001).
The current state of the art public health guidance letters are based on what is known about anthrax bio-terrorism in its short history since the first week of October 2001. (Novello, A. C. “Dear Doctor letter with 6 attachments” Oct. 19, 2001). The guidance document to practicing physicians is the result of epidemiological findings done by the stale department. The guidance document's relevance to the medical management of “Life and Death matter with Inhalation anthrax” is that it has been a fertile ground for medical malpractice involving $37 million lawsuit in Maryland. (Martinez, B. “Anthrax Victim's Son Sues Kaiser Facility His Father Consulted” Wall Street Journal, Nov. 14, 2001).
Anthrax bacillus is an aerobic, Gram-positive organism. The virulence of the bacteria is related to the following critical factors:
1. The capsule: The capsule of anthrax bacilli contains polypeptide of D-glutamic acid. This is unusual. Most gram-positive or grain-negative bacteria capsules have polysaccharides or carbohydrate elements. The unusual nature of the capsule allows bacilli to survive externally, in harsh environmental conditions for decades. Anthrax bacillus infection is not transmitted from patient to healthy person. Yet, the free-floating state in the aerosolized form is extremely dangerous. Subjects are exposed to repeat or fresh infections. Decontamination procedures are extremely cost ineffective over a long period of time. If the area in which contamination occurs involves a large area or a city, its abandonment and sealing is required. Internally, in the living body the capsule facilitates bacterial infection by evading immune responses and resisting phagocytosis inside macrophages. Anti-microbial therapy is not associated with immunity. There is thus a delayed risk of relapse. To reduce the magnitude of these problems cost effective vaccine therapy that is directed to protect against the capsular antigen is needed. In future vaccine strategy, the need to address the problem of immune evasion and the resistance to phagocytosis is emphasized. (Novello, A. C. “Dear Doctor letter with 6 attachments” Oct. 19, 2001).
2. Macrophage: ace inside macrophages, bacilli multiply rapidly secreting polypeptide or proteins that have toxin-like properties. The amino acid composition of the three proteins synthesized by anthrax bacilli lacks a cysteine molecule; therefore they must maintain function in an oxidizing milieu. Macrophage is a preferred home because of its ability to form large amount of reactive oxygen intermediates (ROI). In the early stage, macrophage responds by stock piling large amount of inflammatory cytokines such as TNF Alfa and IL-1B. In the later stage, macrophages burst open and liberate large amounts of inflammatory cytokines. This leads to characteristic high mortality of the host due to sudden septic shock. (Bhatnagar, R and Batra, S. Anthrax Toxin. Crit Rev Microbiol. 2001; 27(3): 167-200).
3. The toxin: In anthrax infection three different types of proteins with toxin like properties are secrete& Synthesis of Protective antigen (PA) is critical. This protein As combines with other synthesized proteins such as Edema factor (EF) and/or Lethal factor (LF) to impart its toxicity. PA also binds with cell receptor of the host cell. It is clipped by host tissue serine proteases such as chymotrypsin and furin to PA 63. PA 63 facilitates the translocation of EF and LF in to the cytosol. Toxin manifests its cytotoxic effects in the cytoplasm. Thus formation of membrane attack complex on the self or host tissues and its translocation inside cells is critical before toxic effects of proteins is manifested. Appropriate vaccine strategy involving PA is expected to provide effective immune defenses against mortality due to toxins. EF is also a factor that is involved in immune evasion. Therefore, in future vaccine strategy, the problem of immune evasion should be addressed. (Novello, A. C. “Dear Doctor letter with 6 attachments” Oct. 19, 2001; Bhatnagar, R. and Batra, S. Anthrax Toxin. Crit Rev Microbiol. 2001; 27(3): 167-200).
The key to the understanding of anthrax pathogenesis is the working of the human defense system. The New England Journal of Medicine published a complex series of articles under the title “Recent Advances of Immunology” from July 2000. Based on this and other reference documents (Walport, M. J. Advances in Immunology: Complement: First of two parts. N Engl J Med. 2001; 344:1058-1066; Pangbum, M. K Alternate Pathway: Activation and regulation, the complement system. Edited by Rother K., Till G. O., and Hansch G. M. Springer, 1998, 93-115; Antimicrobial Defenses, Chapter 19, Biochemical Pathways: An Atlas of Biochemistry and Molecular Biology. Edited by Michal, G. Willey J. Publication, 2000; Sahu A. and Lambris J. Structure and biology of complement protein C3, a connecting link between innate and adaptive immunity. Immunological Reviews, 2001, 180: 35-48; Kilpatrick J. M., Babu Y. S., Agrawal A. et al. Control of the Alternate Complement Pathways: inhibition of Factor D, Controlling the Complement System: For Novel Drug Development. Edited by Mazarakis, H., Swart, S. J., IBC Inc Publication. 1997, 13: 203-225; Rustaggi P. K., Kilpatrick J. M., Niwas S. et al. Development of Novel Broad Spectrum Serine Protease Inhibitors for use as Anticoagulants: Chapter 15, Anticoagulant, Antithrombotics and Thrombolytic Therapeutics, IBC Inc. 1998; II-1924: 307-319; Pangburn M. K. Review: Host recognition and target differentiation by Factor H, a regulator of the Alternative pathway of the complement, lmmunopharmacology. 2000, 49:149-157; Zipfel P. F. et al.
Keusey, Tutunjian & & Bitetto, P.C.
Portner Ginny Allen
Smith Lynette R. F.
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