Proteins, genes and their use for diagnosis and treatment of kidney response
First Claim
1. A method for screening, diagnosis or prognosis of kidney response in a subject, for determining the stage or severity of kidney response in a subject, for identifying a subject at risk of developing kidney response, or for monitoring the effect of therapy administered to a subject having kidney response, said method comprising:
- (a) analyzing a test sample of tissue or body fluid from the subject by two dimensional electrophoresis to generate a two-dimensional array of features, said array comprising one or more Kidney Response-Associated Features (KRF)s selected from the group consisting of KRF-1, KRF-2, KRF-3, KRF-4, KRF-5, KRF-6, KRF-7, KRF-8, KRF-9, KRF-10, KRF-11, KRF-12, KRF-13, KRF-14, KRF-15, KRF-16, KRF-17, KRF-18, KRF-19, KRF-20, KRF-21, KRF-22, KRF-23, KRF-24, KRF-25, KRF-26, KRF-27, KRF-28, KRF-29, KRF-30, KRF-31, KRF-32, KRF-33, KRF-34, KRF-35, KRF-36, KRF-37, KRF-38, KRF-39, KRF-40, KRF-41, KRF-42, KRF-43, KRF-44, KRF-45, KRF-46, KRF-47, KRF-48, KRF-49, KRF-50, KRF-51, KRF-52, KRF-53, KRF-54, KRF-55, KRF-56, KRF-57, KRF-58, KRF-59, KRF-60, KRF-61, KRF-62, KRF-63, KRF-64, KRF-65, KRF-66, KRF-67, KRF-68, KRF-69, KRF-70, KRF-71, KRF-72, KRF-73, KRF-74, KRF-75, KRF-76, KRF-77, KRF-78, KRF-79, KRF-80, KRF-81, KRF-82, KRF-83, KRF-84, KRF-85, KRF-86, KRF-87, KRF-88, KRF-89, KRF-90, KRF-91, KRF-92, KRF-93, KRF-94, KRF-95, KRF-96, KRF-97, KRF-98, KRF-99, KRF-100, KRF-101, KRF-102, KRF-103, KRF-104, KRF-105, KRF-106, KRF-107, KRF-108, KRF-109, KRF-110, KRF-111, KRF-112, KRF-113, KRF-114, KRF-115, KRF-116, KRF-117, KRF-118, KRF-119, KRF-120, KRF-121, KRF-122, KRF-123, KRF-124, KRF-125, KRF-126, KRF-127, KRF-128, KRF-129, KRF-130, KRF-131, KRF-132, KRF-133, KRF-134, KRF-135, KRF-136, KRF-137, KRF-138, KRF-139, KRF-140, KRF-141, KRF-142, KRF-143, KRF-144, KRF-145, KRF-146, KRF-147, KRF-148, KRF-149, KRF-150, KRF-151, KRF-152, KRF-153, KRF-154, KRF-155, KRF-156, KRF-157, KRF-158, KRF-159, KRF-160, KRF-161, KRF-162, KRF-163, KRF-164, KRF-165, KRF-166, KRF-167, KRF-168, KRF-169, KRF-170, KRF-171, KRF-172, KRF-173, KRF-174, KRF-175, KRF-176, KRF-177, KRF-178, KRF-179, KRF-180, KRF-181, KRF-182, KRF-183, KRF-184, KRF-185, KRF-186, KRF-187, KRF-188, KRF-189, KRF-190, KRF-191, KRF-192, KRF-193, KRF-194, KRF-195, KRF-196, KRF-197, KRF-198, KRF-199, KRF-200, KRF-201, KRF-202, KRF-203, KRF-204, KRF-205, KRF-206, KRF-207, KRF-208, KRF-209, KRF-210, KRF-211, KRF-212, KRF-213, KRF-214, KRF-215, KRF-216, KRF-217, KRF-218, KRF-219, KRF-220, KRF-221, KRF-222, KRF-223, KRF-224, KRF-225, KRF-226, KRF-227, KRF-228, KRF-229, KRF-230, KRF-231, KRF-232, KRF-233, KRF-234, KRF-235, KRF-236, KRF-237, KRF-238, KRF-239, KRF-240, KRF-241, KRF-242, KRF-243, KRF-244, KRF-245, KRF-246, KRF-247, KRF-248, KRF-249, KRF-250, KRF-251, KRF-252, KRF-253, KRF-254, KRF-255, KRF-256, KRF-257, KRF-258, KRF-259, KRF-260, KRF-261, KRF-262, KRF-263, KRF-264, KRF-265, KRF-266, KRF-267, KRF-268, KRF-269, KRF-270, KRF-271, KRF-272, KRF-273, KRF-274, KRF-275, KRF-276, KRF-277, KRF-278, KRF-279, KRF-280, KRF-281, KRF-282, KRF-283, KRF-284, KRF-285, KRF-286, KRF-287, KRF-288, KRF-289, KRF-290, KRF-291, KRF-292, KRF-293, KRF-294, KRF-295, KRF-296, KRF-297, KRF-298, KRF-299, KRF-300, KRF-301, KRF-302, KRF-303, KRF-304, KRF-305, KRF-306, KRF-307, KRF-308, KRF-309, KRF-310, KRF-311, KRF-312, KRF-313, KRF-314, KRF-315, KRF-316, KRF-317, KRF-318, KRF-319, KRF-320, KRF-321, KRF-322, KRF-323, KRF-324, KRF-325, KRF-326, KRF-327, KRF-328, KRF-329, KRF-330, KRF-331, KRF-332, KRF-333, KRF-334, KRF-335, KRF-336, KRF-337, KRF-338, KRF-339, KRF-340, KRF-341, KRF-342, KRF-343, KRF-344, KRF-345, KRF-346, KRF-347, KRF-348, KRF-349, KRF-350, KRF-351 and KRF-352, whose relative abundance correlates with the presence, absence, stage or severity of kidney response or predicts the onset or course of kidney response; and
(b) comparing the abundance of each selected feature in the test sample with the abundance of that chosen feature in tissue or body fluid from one or more subjects free from kidney response, or with a previously determined reference range for that feature in subjects free from kidney response, or with the abundance at least one Expression Reference Feature (ERF) in the test sample.
1 Assignment
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Accused Products
Abstract
The present invention provides methods and compositions for screening, diagnosis and prognosis of kidney response, for monitoring the effectiveness of kidney response treatment, identifying patients most likely to respond to a particular therapeutic treatment and for drug development. In particular, the screening of drug candidates for their ability to induce a kidney response. Kidney Response-Associated Features (KRFs), detectable by two-dimensional electrophoresis of blood, serum, plasma or kidney tissue are described. The invention further provides Kidney Response-Associated Protein Isoforms (KRPIs) detectable in blood, serum, plasma or kidney tissue, preparations comprising isolated KRPIs, antibodies immunospecific for KRPIs, and kits comprising the aforesaid.
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Citations
19 Claims
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1. A method for screening, diagnosis or prognosis of kidney response in a subject, for determining the stage or severity of kidney response in a subject, for identifying a subject at risk of developing kidney response, or for monitoring the effect of therapy administered to a subject having kidney response, said method comprising:
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(a) analyzing a test sample of tissue or body fluid from the subject by two dimensional electrophoresis to generate a two-dimensional array of features, said array comprising one or more Kidney Response-Associated Features (KRF)s selected from the group consisting of KRF-1, KRF-2, KRF-3, KRF-4, KRF-5, KRF-6, KRF-7, KRF-8, KRF-9, KRF-10, KRF-11, KRF-12, KRF-13, KRF-14, KRF-15, KRF-16, KRF-17, KRF-18, KRF-19, KRF-20, KRF-21, KRF-22, KRF-23, KRF-24, KRF-25, KRF-26, KRF-27, KRF-28, KRF-29, KRF-30, KRF-31, KRF-32, KRF-33, KRF-34, KRF-35, KRF-36, KRF-37, KRF-38, KRF-39, KRF-40, KRF-41, KRF-42, KRF-43, KRF-44, KRF-45, KRF-46, KRF-47, KRF-48, KRF-49, KRF-50, KRF-51, KRF-52, KRF-53, KRF-54, KRF-55, KRF-56, KRF-57, KRF-58, KRF-59, KRF-60, KRF-61, KRF-62, KRF-63, KRF-64, KRF-65, KRF-66, KRF-67, KRF-68, KRF-69, KRF-70, KRF-71, KRF-72, KRF-73, KRF-74, KRF-75, KRF-76, KRF-77, KRF-78, KRF-79, KRF-80, KRF-81, KRF-82, KRF-83, KRF-84, KRF-85, KRF-86, KRF-87, KRF-88, KRF-89, KRF-90, KRF-91, KRF-92, KRF-93, KRF-94, KRF-95, KRF-96, KRF-97, KRF-98, KRF-99, KRF-100, KRF-101, KRF-102, KRF-103, KRF-104, KRF-105, KRF-106, KRF-107, KRF-108, KRF-109, KRF-110, KRF-111, KRF-112, KRF-113, KRF-114, KRF-115, KRF-116, KRF-117, KRF-118, KRF-119, KRF-120, KRF-121, KRF-122, KRF-123, KRF-124, KRF-125, KRF-126, KRF-127, KRF-128, KRF-129, KRF-130, KRF-131, KRF-132, KRF-133, KRF-134, KRF-135, KRF-136, KRF-137, KRF-138, KRF-139, KRF-140, KRF-141, KRF-142, KRF-143, KRF-144, KRF-145, KRF-146, KRF-147, KRF-148, KRF-149, KRF-150, KRF-151, KRF-152, KRF-153, KRF-154, KRF-155, KRF-156, KRF-157, KRF-158, KRF-159, KRF-160, KRF-161, KRF-162, KRF-163, KRF-164, KRF-165, KRF-166, KRF-167, KRF-168, KRF-169, KRF-170, KRF-171, KRF-172, KRF-173, KRF-174, KRF-175, KRF-176, KRF-177, KRF-178, KRF-179, KRF-180, KRF-181, KRF-182, KRF-183, KRF-184, KRF-185, KRF-186, KRF-187, KRF-188, KRF-189, KRF-190, KRF-191, KRF-192, KRF-193, KRF-194, KRF-195, KRF-196, KRF-197, KRF-198, KRF-199, KRF-200, KRF-201, KRF-202, KRF-203, KRF-204, KRF-205, KRF-206, KRF-207, KRF-208, KRF-209, KRF-210, KRF-211, KRF-212, KRF-213, KRF-214, KRF-215, KRF-216, KRF-217, KRF-218, KRF-219, KRF-220, KRF-221, KRF-222, KRF-223, KRF-224, KRF-225, KRF-226, KRF-227, KRF-228, KRF-229, KRF-230, KRF-231, KRF-232, KRF-233, KRF-234, KRF-235, KRF-236, KRF-237, KRF-238, KRF-239, KRF-240, KRF-241, KRF-242, KRF-243, KRF-244, KRF-245, KRF-246, KRF-247, KRF-248, KRF-249, KRF-250, KRF-251, KRF-252, KRF-253, KRF-254, KRF-255, KRF-256, KRF-257, KRF-258, KRF-259, KRF-260, KRF-261, KRF-262, KRF-263, KRF-264, KRF-265, KRF-266, KRF-267, KRF-268, KRF-269, KRF-270, KRF-271, KRF-272, KRF-273, KRF-274, KRF-275, KRF-276, KRF-277, KRF-278, KRF-279, KRF-280, KRF-281, KRF-282, KRF-283, KRF-284, KRF-285, KRF-286, KRF-287, KRF-288, KRF-289, KRF-290, KRF-291, KRF-292, KRF-293, KRF-294, KRF-295, KRF-296, KRF-297, KRF-298, KRF-299, KRF-300, KRF-301, KRF-302, KRF-303, KRF-304, KRF-305, KRF-306, KRF-307, KRF-308, KRF-309, KRF-310, KRF-311, KRF-312, KRF-313, KRF-314, KRF-315, KRF-316, KRF-317, KRF-318, KRF-319, KRF-320, KRF-321, KRF-322, KRF-323, KRF-324, KRF-325, KRF-326, KRF-327, KRF-328, KRF-329, KRF-330, KRF-331, KRF-332, KRF-333, KRF-334, KRF-335, KRF-336, KRF-337, KRF-338, KRF-339, KRF-340, KRF-341, KRF-342, KRF-343, KRF-344, KRF-345, KRF-346, KRF-347, KRF-348, KRF-349, KRF-350, KRF-351 and KRF-352, whose relative abundance correlates with the presence, absence, stage or severity of kidney response or predicts the onset or course of kidney response; and
(b) comparing the abundance of each selected feature in the test sample with the abundance of that chosen feature in tissue or body fluid from one or more subjects free from kidney response, or with a previously determined reference range for that feature in subjects free from kidney response, or with the abundance at least one Expression Reference Feature (ERF) in the test sample. - View Dependent Claims (2, 3, 4, 5, 6)
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7. A method for screening, diagnosis or prognosis of kidney response in a subject, for determining the stage or severity of kidney response in a subject, for identifying a subject at risk of developing kidney response, or for monitoring the effect of therapy administered to a subject having kidney response, said method comprising:
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(a) quantitatively detecting, in a sample of kidney tissue from the subject, at least one Kidney Response-Associated Protein Isoform (KRPI) selected from the group consisting of;
KRPI-2, KRPI-8, KRPI-11, KRPI-13, KRPI-14, KRPI-15, KRPI-16, KRPI-19, KRPI-21, KRPI-23, KRPI-27, KRPI-28, KRPI-35, KRPI-40, KRPI-41, KRPI-42, KRPI-43, KRPI-45.1, KRPI-45.2, KRPI-57, KRPI-59, KRPI-60, KRPI-63, KRPI-70, KRPI-72, KRPI-73, KRPI-76, KRPI-84, KRPI-85, KRPI-86, KRPI-88, KRPI-90, KRPI-91, KRPI-98, KRPI-101, KRPI-104, KRPI-105, KRPI-113, KRPI-122, KRPI-123, KRPI-128, KRPI-131, KRPI-132, KRPI-134, KRPI-138, KRPI-139, KRPI-142, KRPI-143, KRPI-144, KRPI-149, KRPI-152, KRPI-153, KRPI-158, KRPI-159, KRPI-168, KRPI-170, KRPI-178, KRPI-179, KRPI-183, KRPI-184, KRPI-185, KRPI-186, KRPI-188, KRPI-189.1, KRPI-189.2, KRPI-192, KRPI-196, KRPI-202, KRPI-206, KRPI-208, KRPI-210, KRPI-219, KRPI-222, KRPI-229, KRPI-232, KRPI-235.1, KRPI-235.2, KRPI-236, KRPI-237, KRPI-240, KRPI-245, KRPI-247, KRPI-249, KRPI-250, KRPI-252, KRPI-253, KRPI-256, KRPI-257, KRPI-263, KRPI-267, KRPI-273, KRPI-278, KRPI-280, KRPI-282, KRPI-285 and KRPI-286, and(b) comparing the level or amount of said isoform or isoforms detected in step (a) with a control. - View Dependent Claims (8, 9, 10, 18)
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11. A method for screening, diagnosis or prognosis of kidney response in a subject, for determining the stage or severity of kidney response in a subject, for identifying a subject at risk of developing kidney response, or for monitoring the effect of therapy administered to a subject having kidney response, said method comprising:
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(a) quantitatively detecting, in a sample of blood, serum or plasma from the subject, at least one Kidney Response-Associated Protein Isoform (KRPI) selected from the group consisiting of;
KRPI-313, KRPI-314.1, KRPI-314.2, KRPI-327.1, KRPI-327.2 and KRPI-339, and(b) comparing the level or amount of said isoform or isoforms detected in step (a) with a control. - View Dependent Claims (12, 13, 14, 19)
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15. A method for screening, diagnosis or prognosis of kidney response in a subject, for determining the stage or severity of kidney response in a subject, for identifying a subject at risk of developing kidney response, or for monitoring the effect of therapy administered to a subject having kidney response, said method comprising:
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(a) contacting at least one oligonucleotide probe comprising 10 or more consecutive nucleotides complementary to a nucleotide sequence encoding a KRPI selected from the group consisting of KRPI-2, KRPI-8, KRPI-11, KRPI-13, KRPI-14, KRPI-15, KRPI-16, KRPI-19, KRPI-21, KRPI-23, KRPI-27, KRPI-28, KRPI-35, KRPI-40, KRPI-41, KRPI-42, KRPI-43, KRPI-45.1, KRPI-45.2, KRPI-57, KRPI-59, KRPI-60, KRPI-63, KRPI-70, KRPI-72, KRPI-73, KRPI-76, KRPI-84, KRPI-85, KRPI-86, KRPI-88, KRPI-90, KRPI-91, KRPI-98, KRPI-101, KRPI-104, KRPI-105, KRPI-113, KRPI-122, KRPI-123, KRPI-128, KRPI-131, KRPI-132, KRPI-134, KRPI-138, KRPI-139, KRPI-142, KRPI-143, KRPI-144, KRPI-149, KRPI-152, KRPI-153, KRPI-158, KRPI-159, KRPI-168, KRPI-170, KRPI-178, KRPI-179, KRPI-183, KRPI-184, KRPI-185, KRPI-186, KRPI-188, KRPI-189.1, KRPI-189.2, KRPI-192, KRPI-196, KRPI-202, KRPI-206, KRPI-208, KRPI-210, KRPI-219, KRPI-222, KRPI-229, KRPI-232, KRPI-235.1, KRPI-235.2, KRPI-236, KRPI-237, KRPI-240, KRPI-245, KRPI-247, KRPI-249, KRPI-250, KRPI-252, KRPI-253, KRPI-256, KRPI-257, KRPI-263, KRPI-267, KRPI-273, KRPI-278, KRPI-280, KRPI-282, KRPI-285, KRPI-286, KRPI-313, KRPI-314.1, KRPI-314.2, KRPI-327.1, KRPI-327.2 and KRPI-339 and orthologs thereof, with an RNA obtained from a biological sample from the subject or with cDNA copied from the RNA wherein said contacting occurs under conditions that permit hybridization of the probe to the nucleotide sequence if present;
(b) detecting hybridization, if any, between the probe and the nucleotide sequence; and
(c) comparing the hybridization, if any, detected in step (b) with the hybridization detected in a control sample, or with a previously determined reference range. - View Dependent Claims (16, 17)
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Specification