Patent number 8623369 is assigned to
The following quote was obtained by the news editors from the background information supplied by the inventors: "Cardiovascular diseases are currently the leading cause of death in developed countries, and represent a growing financial burden on health care. Atherosclerosis, the narrowing of major arteries by fatty plaques, constitutes the single most important contributor to this group of diseases. However, in over half of affected individuals, the condition is left undetected and the earliest clinical manifestations are myocardial infarction, stroke, or sudden death. In particular, carotid artery stenosis (carotid artery disease--CAD), is responsible for approximately half of ischemic strokes, and is mostly caused by carotid atherosclerosis.
"Landmark clinical trials over the past two decades have demonstrated that surgical intervention in cases of symptomatic high-grade stenosis can reduce the risk of subsequent stroke (Barnett et al, 1998; Ferguson et al 1999; Gillard, 2003). However, it has also been shown that the degree of stenosis is not predictive of risk for stroke; it is rather the presence of unstable, inflamed atherosclerotic plaques that is a more accurate predictor of impending stroke. Therefore, screening patients diagnosed with CAD for carotid atherosclerosis is recommended; however, such screening (MRI or X-ray angiography) might be costly.
"Surgical treatment for CAD is performed via a procedure called endarterectomy, which typically comprises surgical removal of plaques from the artery, but unfortunately carries a high mortality risk of 2-10%. To justify such a high mortality risk and qualify patients for high-risk endarcterectomy, it is necessary to more accurately diagnose CAD caused by unstable atherosclerotic plaques, which are predictive of stroke.
"Most patients with ischemic stroke or transient ischemic attack are screened for internal carotid artery stenosis. The current standard of care for detecting carotid stenosis is based on conventional imaging techniques such as ultrasound and angiography. These methods provide information about the structural consequences of CAD, such as luminal stenosis, but yield little to no information about plaque development and plaque characteristics within the vessel wall. None of these imaging techniques is able to provide information on the molecular or cellular events within the plaque that predispose it to rupture (i.e., an unstable plaque), and hence predict the real risk for stroke.
"X-ray angiography remains the current gold standard imaging technique; however, it has many limitations. Angiography simply images the lumen of the vessel, and fails to detect atherosclerotic lesions that do not protrude into the lumen and provides little information on atherosclerotic plaque composition. Thus, it cannot differentiate between unstable and stable plaques and, therefore, is unable to predict the risk of plaque rupture. Consequently, because it is mostly symptom-driven, its main value is in delineating the causative lesion in a symptomatic patient. However, because of positive remodelling, a `normal` angiogram cannot be interpreted as indicating an absence of atherosclerosis. Moreover, MRI and x-ray angiography screenings are costly.
"Therefore, there remains a need in the art for a cost-effective method of screening atherosclerotic plaques to identify unstable plaques and more accurately predict the risk of rupture for heart attack and stroke."
In addition to the background information obtained for this patent, NewsRx journalists also obtained the inventors' summary information for this patent: "The present invention relates to anti-
"The present invention provides an isolated or purified antibody or fragment thereof specific to intercellular adhesion molecule 1 (
"The antibody or fragment thereof may have a CDR1 of sequence LYVMG (SEQ ID NO:1), a CDR2 of sequence DITSSGSIYYVDSLKG (SEQ ID NO:4), and a CDR3 of sequence HVRQDSGSEYLTY (SEQ ID NO:7). Alternatively, the antibody or fragment thereof may have a CDR1 of sequence AFRMG (SEQ ID NO:2), a CDR2 of sequence VITAGGTTSYIDSVKG (SEQ ID NO:5), and a CDR3 of sequence IDYDS (SEQ ID NO:8). In yet another alternative, the antibody or fragment thereof may have a CDR1 of sequence INDMG (SEQ ID NO:3), a CDR2 of sequence RITRDGSAAYEDSVKG (SEQ ID NO:6), and a CDR3 of sequence EIITTQTLGRMLGEY (SEQ ID NO:9).
"The isolated or purified antibody or fragment thereof may be a single-domain antibody (sdAb); the sdAb may be of camelid origin. In one specific, non-limiting example, the isolated or purified antibody or fragment thereof may comprise the sequence:
"TABLE-US-00001 (SEQ ID NO: 10) QVQLVESGGGLVQPGGSLRLSCAASGSISSLYVMGWYRQAPGKQRELV ADITSSGSIYYVDSLKGRFTISRDNARSTVYLQMNSLEPEDTAVYYCM AHVRQDSGSEYLTYWGQGTQVTVSS, (SEQ ID NO: 11) QVKLEESGGGLVQAGDSLRLSCAASGRTVNAFRMGWYRQAPGKQRERV AVITAGGTTSYIDSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCA AIDYDSRGQGTQVTVSS, or (SEQ ID NO: 12) QVKLEESGGGLVQPGGSLRLSCAASGSIFSINDMGWYRQAPGKQRELV ARITRDGSAAYEDSVKGRFTISRDNAPNTVFLQMNGLKPEDTAVYYCN AEIITTQTLGRMLGEYWGQGTQVTVSS,
"or a sequence substantially identical thereto.
"The invention also provides nucleic acid sequences encoding the anti-
"The present invention further provides a targeted therapeutic agent comprising an antibody or fragment thereof of the present invention linked to a suitable therapeutic. The antibody or fragment thereof may serve to target therapeutic agents to the site of atherosclerotic plaques, or may have use as a therapeutic agent itself. In a non-limiting example, the antibody or fragment thereof or targeted therapeutic agent may be used for: therapeutically modifying the inflammatory component of atherosclerotic disease (e.g., stroke prevention therapy), or to treat conditions associated with increased
"The present invention further provides a molecular imaging agent comprising an antibody or fragment thereof in accordance with the present invention linked to a detectable agent. For example, the anti-
"The present invention also provides an ex vivo method of detecting atherosclerotic plaque diseases involving inflammation, comprising: a) providing a tissue sample suspected of inflammation and plaque formation; b) contacting said sample with an anti-
"The present invention also provides an in vivo method of detecting atherosclerotic plaque diseases involving inflammation, comprising: a) administering the molecular imaging agent of the present invention to a subject; and b) detecting the binding of the molecular imaging agent, wherein the molecular imaging agent binds to binds
"The present invention also provides a method of detecting conditions characterized with increased expression of
"The in vivo detection step in the methods described above may be whole body imaging for diagnostic purposes or local imaging at specific sites, such as carotid and aortic arteries, in a quantitative manner to assess the progression of disease or host response to a treatment regimen.
"The methods as described herein may be used to monitor the progression or regression of disease over time. The methods described herein may also be used to monitor the efficacy of therapy, for example but not limited to drugs such as statins in the treatment of atheroslerosis.
"The present invention further provides a method for diagnosing a clinical condition associated with
"Anti-ICAM-1 single-domain antibodies were obtained by immunization of a llama with
"The use of sdAb is advantageous as they may be produced easily and inexpensively in large quantities, as opposed to antibodies produced from hybridoma cell lines. Additionally, hybridoma lines may be unstable and decrease antibody expression levels over time. sdAb are also advantageous for molecular imaging applications due to their short plasma half-life, which achieves fast contrast-to-noise ratio needed for imaging.
"Additional aspects and advantages of the present invention will be apparent in view of the following description. The detailed description and examples, while indicating preferred embodiments of the invention, are given by way of illustration only, as various changes and modifications within the scope of the invention will become apparent to those skilled in the art in light of the teachings of this invention."
URL and more information on this patent, see: Abulrob, Abedelnasser; Arbabi-Ghahroudi, Mehdi; Stanimirovic, Danica. Anti-
Keywords for this news article include: Antibodies, Therapy, Treatment, Immunology, Blood Proteins, Nanotechnology, Immunoglobulins, Molecular Imaging, Emerging Technologies,
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