DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 7/24/2026 is acknowledged. The election of species, (A) the GRP78-binding agent recited in claim 2 of the present application; and (B) the Lutetium-177 (¹⁷⁷Lu) radiolabel recited in claim 5 of the present application, are also acknowledged. Claims 1-21 are pending, of which claims 6 and 15-21 are withdrawn from consideration at this time as being directed to a non-elected invention or species. Claims 1-5 and 7-14 encompass the elected invention and species and are examined herein on the merits for patentability.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-4, 7 and 12-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kapoor et al. (US 2017/0290929).
Kapoor discloses a conjugate of formula (I): P-(X-D)n, wherein P is a peptide that binds to a glucose regulated protein 78 (GRP78); X is a direct bond or a linking group; D is a detectable agent; and n is 1 to 4. Certain embodiments of the invention provide a pharmaceutical composition comprising a conjugate of formula (I) and a pharmaceutically acceptable excipient. Certain embodiments of the invention provide a method for treating or preventing cancer in an animal (e.g., a human) comprising administering a therapeutically effective amount of a conjugate of formula (I) (e.g., a conjugate comprising a therapeutic radionuclide) to the animal (abstract).
A method for treating or preventing cancer in an animal (e.g., a human) is taught comprising administering a therapeutically effective amount of a conjugate of formula (I) (e.g., a conjugate comprising a therapeutic radionuclide) to the animal (paragraph 0013).
In Figure 1, PEP42 (CTVALPGGYVRKC) is a 13 amino acid cyclized peptide sequence which is believed to bind with GRP 78 with high specificity. FIG. 1A shows chemical structures of N-terminus conjugated DOTA and fluorescein conjugates of PEP42. FIG. 1B shows chemical structures of Lys-conjugated DOTA and fluorescein conjugates of PEP42. FIG. 1C is the pictorial representation of the PEP42 analogs.
Described herein are molecules (e.g., small amino acid sequences, i.e., peptides) that are designed to bind to cell surface GRP78. In certain embodiments, these molecules comprise a chelator that can be labeled with a radionuclide for diagnostic imaging (e.g., PET imaging) or radiation therapy for cancer (paragraph 0047).
As used herein, a “detectable radionuclide” is any suitable radionuclide (i.e., a radioisotope) useful in an imaging procedure, e.g., a diagnostic procedure, in vivo or in vitro, or for, e.g., therapy, e.g., cancer therapy. Suitable detectable radionuclides include metallic radionuclides (i.e., metallic radioisotopes). Suitable metallic radionuclides (i.e., metallic radioisotopes or metallic paramagnetic ions) include Antimony-124, Antimony-125, Arsenic-74, Barium-103, Barium-140, Beryllium-7, Bismuth-206, Bismuth-207, Cadmium-109, Cadmium-115m, Calcium-45, Cerium-139, Cerium-141, Cerium-144, Cesium-137, Chromium-51, Cobalt-55, Cobalt-56, Cobalt-57, Cobalt-58, Cobalt-60, Cobalt-64, Copper-64, Copper-67, Erbium-169, Europium-152, Gallium-64, Gallium-68, Gadolinium-153, Gadolinium-157 Gold-195, Gold-199, Hafnium-175, Hafnium-175-181, Holmium-166, Indium-110, Indium-111, Iridium-192, Iron-55, Iron-59, Krypton-85, Lead-210, Manganese-54, Mercury-197, Mercury-203, Molybdenum-99, Neodymium-147, Neptunium-237, Nickel-63, Niobium-95, Osmium-185+191, Palladium-103, Platinum-195m, Praseodymium-143, Promethium-147, Protactinium-233, Radium-226, Rhenium-186, Rhenium-188, Rubidium-86, Ruthenium-103, Ruthenium-106, Scandium-44, Scandium-46, Selenium-75, Silver-110m, Silver-111, Sodium-22, Strontium-85, Strontium-89, Strontium-90, Sulfur-35, Tantalum-182, Technetium-99m, Tellurium-125, Tellurium-132, Thallium-204, Thorium-228, Thorium-232, Thallium-170, Tin-113, Tin-114, Tin-117m, Titanium-44, Tungsten-185, Vanadium-48, Vanadium-49, Ytterbium-169, Yttrium-86, Yttrium-88, Yttrium-90, Yttrium-91, Zinc-65, and Zirconium-95. In certain embodiments, the radionuclide is Gallium-68, Copper-64 or Yttrium-90 (paragraph 0157-8).
The phrase “therapeutically effective amount” means an amount of a compound of the present invention that (i) treats the particular disease, condition, or disorder, (ii) attenuates, ameliorates, or eliminates one or more symptoms of the particular disease, condition, or disorder, or (iii) prevents or delays the onset of one or more symptoms of the particular disease, condition, or disorder described herein. In the case of cancer, the therapeutically effective amount of the drug may reduce the number of cancer cells; reduce the tumor size; inhibit (i.e., slow to some extent and preferably stop) cancer cell infiltration into peripheral organs; inhibit (i.e., slow to some extent and preferably stop) tumor metastasis; inhibit, to some extent, tumor growth; and/or relieve to some extent one or more of the symptoms associated with the cancer. To the extent the drug may prevent growth and/or kill existing cancer cells, it may be cytostatic and/or cytotoxic. For cancer therapy, efficacy can be measured, for example, by assessing the time to disease progression (TTP) and/or determining the response rate (RR).
Cancers include carcinoma…, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, anal carcinoma, penile carcinoma, head and neck cancer, and melanoma.
GRP78 is a 78 kDa molecular chaperone that resides primarily in the endoplasmic reticulum however emerging evidences have shown translocation of GRP78 on the cell surface in the tumor microenvironment (Amy. S. Lee Cancer Res (2007); 77:3496-3499). As described herein the potential of GRP78 targeted peptides for molecular imaging and targeted radionuclide therapy were evaluated. Two sets of GRP78 targeted peptides were synthesized. The PEP42 analogues (N-DOTA/flourescein-PEP42 and Lys-DOTA/flourescein-PEP42) are 13-mer cyclized peptides in which the position of DOTA was varied (paragraph 0238).
With regard to the limitation wherein the GRP78-binding agent induces endoplasmic reticulum stress and activates deoxyribonucleic acid damage response in a cancerous tissue including cell-surface GRP78 in the subject, it is noted that “Products of identical chemical composition cannot have mutually exclusive properties.” A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure or composition as that which is claimed, the properties applicant discloses and/or claims are necessarily present. See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). The “discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” See Atlas Power Co. v. Ireco Inc., 51 USPQ 2d 1943, 1947 (Fed. Cir. 1999). Therefore, merely claiming a new use, new function, or new property, which is inherently present in the prior art does not make the claim patentable. See In re Best, 195 USPQ 430, 433 (CCPA 1977), and MPEP § 2112.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-5, 7, 9 and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Kapoor et al. (US 2017/0290929) in view of Ludwig et al. (US 2024/0390532).
Kapoor teaches a conjugate of formula (I): P-(X-D)n, wherein P is a peptide that binds to a glucose regulated protein 78 (GRP78); X is a direct bond or a linking group; D is a detectable agent; and n is 1 to 4. Certain embodiments of the invention provide a pharmaceutical composition comprising a conjugate of formula (I) and a pharmaceutically acceptable excipient. Certain embodiments of the invention provide a method for treating or preventing cancer in an animal (e.g., a human) comprising administering a therapeutically effective amount of a conjugate of formula (I) (e.g., a conjugate comprising a therapeutic radionuclide) to the animal (abstract).
A method for treating or preventing cancer in an animal (e.g., a human) is taught comprising administering a therapeutically effective amount of a conjugate of formula (I) (e.g., a conjugate comprising a therapeutic radionuclide) to the animal (paragraph 0013).
In Figure 1, PEP42 (CTVALPGGYVRKC) is a 13 amino acid cyclized peptide sequence which is believed to bind with GRP 78 with high specificity. FIG. 1A shows chemical structures of N-terminus conjugated DOTA and fluorescein conjugates of PEP42. FIG. 1B shows chemical structures of Lys-conjugated DOTA and fluorescein conjugates of PEP42. FIG. 1C is the pictorial representation of the PEP42 analogs.
Described herein are molecules (e.g., small amino acid sequences, i.e., peptides) that are designed to bind to cell surface GRP78. In certain embodiments, these molecules comprise a chelator that can be labeled with a radionuclide for diagnostic imaging (e.g., PET imaging) or radiation therapy for cancer (paragraph 0047).
As used herein, a “detectable radionuclide” is any suitable radionuclide (i.e., a radioisotope) useful in an imaging procedure, e.g., a diagnostic procedure, in vivo or in vitro, or for, e.g., therapy, e.g., cancer therapy. Suitable detectable radionuclides include metallic radionuclides (i.e., metallic radioisotopes). Suitable metallic radionuclides (i.e., metallic radioisotopes or metallic paramagnetic ions) include Antimony-124, Antimony-125, Arsenic-74, Barium-103, Barium-140, Beryllium-7, Bismuth-206, Bismuth-207, Cadmium-109, Cadmium-115m, Calcium-45, Cerium-139, Cerium-141, Cerium-144, Cesium-137, Chromium-51, Cobalt-55, Cobalt-56, Cobalt-57, Cobalt-58, Cobalt-60, Cobalt-64, Copper-64, Copper-67, Erbium-169, Europium-152, Gallium-64, Gallium-68, Gadolinium-153, Gadolinium-157 Gold-195, Gold-199, Hafnium-175, Hafnium-175-181, Holmium-166, Indium-110, Indium-111, Iridium-192, Iron-55, Iron-59, Krypton-85, Lead-210, Manganese-54, Mercury-197, Mercury-203, Molybdenum-99, Neodymium-147, Neptunium-237, Nickel-63, Niobium-95, Osmium-185+191, Palladium-103, Platinum-195m, Praseodymium-143, Promethium-147, Protactinium-233, Radium-226, Rhenium-186, Rhenium-188, Rubidium-86, Ruthenium-103, Ruthenium-106, Scandium-44, Scandium-46, Selenium-75, Silver-110m, Silver-111, Sodium-22, Strontium-85, Strontium-89, Strontium-90, Sulfur-35, Tantalum-182, Technetium-99m, Tellurium-125, Tellurium-132, Thallium-204, Thorium-228, Thorium-232, Thallium-170, Tin-113, Tin-114, Tin-117m, Titanium-44, Tungsten-185, Vanadium-48, Vanadium-49, Ytterbium-169, Yttrium-86, Yttrium-88, Yttrium-90, Yttrium-91, Zinc-65, and Zirconium-95. In certain embodiments, the radionuclide is Gallium-68, Copper-64 or Yttrium-90 (paragraph 0157-8).
The phrase “therapeutically effective amount” means an amount of a compound of the present invention that (i) treats the particular disease, condition, or disorder, (ii) attenuates, ameliorates, or eliminates one or more symptoms of the particular disease, condition, or disorder, or (iii) prevents or delays the onset of one or more symptoms of the particular disease, condition, or disorder described herein. In the case of cancer, the therapeutically effective amount of the drug may reduce the number of cancer cells; reduce the tumor size; inhibit (i.e., slow to some extent and preferably stop) cancer cell infiltration into peripheral organs; inhibit (i.e., slow to some extent and preferably stop) tumor metastasis; inhibit, to some extent, tumor growth; and/or relieve to some extent one or more of the symptoms associated with the cancer. To the extent the drug may prevent growth and/or kill existing cancer cells, it may be cytostatic and/or cytotoxic. For cancer therapy, efficacy can be measured, for example, by assessing the time to disease progression (TTP) and/or determining the response rate (RR).
Cancers include carcinoma…, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, anal carcinoma, penile carcinoma, head and neck cancer, and melanoma.
GRP78 is a 78 kDa molecular chaperone that resides primarily in the endoplasmic reticulum however emerging evidences have shown translocation of GRP78 on the cell surface in the tumor microenvironment (Amy. S. Lee Cancer Res (2007); 77:3496-3499). As described herein the potential of GRP78 targeted peptides for molecular imaging and targeted radionuclide therapy were evaluated. Two sets of GRP78 targeted peptides were synthesized. The PEP42 analogues (N-DOTA/flourescein-PEP42 and Lys-DOTA/flourescein-PEP42) are 13-mer cyclized peptides in which the position of DOTA was varied (paragraph 0238).
Kapoor does not specifically teach that radionuclide is Lu-177 or that prostate cancer is castration-resistant prostate cancer.
Ludwig teaches a peptide comprising a GRP78 binding amino acid sequence, such as any of those described herein, and a covalently linked chelating moiety (chelator) such as any of those described herein. A related aspect of the invention provides said peptide further including a radionuclide, such as any of those described herein, chelated by the chelating moiety. For example, the chelator may include DOTA or a DOTA derivative and the radionuclide chelated thereby may include 225Ac, 177Lu or 90Y. A further related aspect provides a composition including a peptide, such as a synthetic peptide, including a GRP78 binding amino acid sequence, such as any of those described herein, a chelating moiety (chelator), such as any of those described herein, directly or indirectly covalently linked to the peptide, and a radionuclide that the chelator is capable of chelating, wherein a fraction of the peptide in the composition chelates a radionuclide via the chelator (i.e., is radiolabeled with the radionuclide) and the remaining fraction of the peptide in the composition does not chelate a radionuclide (i.e., is not radiolabeled with a radionuclide) (paragraph 0152).
Still other radiolabeled cancer targeting agents that may be used in combination or conjunction with a radiolabeled GRP78 targeting agent for the treatment of proliferative disorders in a mammal such as a human patient include the following radiolabeled targeting agents: a radiolabeled FAP targeting agent such as 177Lu-FAP-2286to treat, for example, solid tumors or any of the cancers (paragraph 0241).
Cancers inculde castration resistant prostate cancer (CRPC) (paragraph 0058).
CTVALPGGYVRVC is taught as a GRP78 targeting agent (paragraph 0099).
It would have been obvious to one of ordinary skill in the art at the time of the invention to substitute Lu-177 as the therapeutic radionuclide in the compositions taught by Kapoor when the teaching of Kapoor is taken in view of Ludwig. Each of Kapoor and Ludwig are directed to linking a therapeutic radionuclide to a GRP78 targeting agent for cancer treatment. One would have been motivated to do so, with a reasonable expectation of success, because Ludwig teaches Lu-177 to be one of a few suitable radionuclides for chelation by a chelator and use in cancer therapy. While Kapoor does not specifically recite castration-resistant prostate cancer as the prostate cancer which is treated by the compositions, it is known from Ludwig that castration-resistant prostate cancer is one of the suitable cancer conditions which may be treated by the GRP78 targeting agent linked a radionuclide for cancer therapy.
Claim(s) 1-4 and 7-14 are rejected under 35 U.S.C. 103 as being unpatentable over Kapoor et al. (US 2017/0290929) in view of Enriquez et al. (Cancer Res, 2021, 81, 4257–74).
Kapoor teaches a conjugate of formula (I): P-(X-D)n, wherein P is a peptide that binds to a glucose regulated protein 78 (GRP78); X is a direct bond or a linking group; D is a detectable agent; and n is 1 to 4. Certain embodiments of the invention provide a pharmaceutical composition comprising a conjugate of formula (I) and a pharmaceutically acceptable excipient. Certain embodiments of the invention provide a method for treating or preventing cancer in an animal (e.g., a human) comprising administering a therapeutically effective amount of a conjugate of formula (I) (e.g., a conjugate comprising a therapeutic radionuclide) to the animal (abstract).
A method for treating or preventing cancer in an animal (e.g., a human) is taught comprising administering a therapeutically effective amount of a conjugate of formula (I) (e.g., a conjugate comprising a therapeutic radionuclide) to the animal (paragraph 0013).
In Figure 1, PEP42 (CTVALPGGYVRKC) is a 13 amino acid cyclized peptide sequence which is believed to bind with GRP 78 with high specificity. FIG. 1A shows chemical structures of N-terminus conjugated DOTA and fluorescein conjugates of PEP42. FIG. 1B shows chemical structures of Lys-conjugated DOTA and fluorescein conjugates of PEP42. FIG. 1C is the pictorial representation of the PEP42 analogs.
Described herein are molecules (e.g., small amino acid sequences, i.e., peptides) that are designed to bind to cell surface GRP78. In certain embodiments, these molecules comprise a chelator that can be labeled with a radionuclide for diagnostic imaging (e.g., PET imaging) or radiation therapy for cancer (paragraph 0047).
As used herein, a “detectable radionuclide” is any suitable radionuclide (i.e., a radioisotope) useful in an imaging procedure, e.g., a diagnostic procedure, in vivo or in vitro, or for, e.g., therapy, e.g., cancer therapy. Suitable detectable radionuclides include metallic radionuclides (i.e., metallic radioisotopes). Suitable metallic radionuclides (i.e., metallic radioisotopes or metallic paramagnetic ions) include Antimony-124, Antimony-125, Arsenic-74, Barium-103, Barium-140, Beryllium-7, Bismuth-206, Bismuth-207, Cadmium-109, Cadmium-115m, Calcium-45, Cerium-139, Cerium-141, Cerium-144, Cesium-137, Chromium-51, Cobalt-55, Cobalt-56, Cobalt-57, Cobalt-58, Cobalt-60, Cobalt-64, Copper-64, Copper-67, Erbium-169, Europium-152, Gallium-64, Gallium-68, Gadolinium-153, Gadolinium-157 Gold-195, Gold-199, Hafnium-175, Hafnium-175-181, Holmium-166, Indium-110, Indium-111, Iridium-192, Iron-55, Iron-59, Krypton-85, Lead-210, Manganese-54, Mercury-197, Mercury-203, Molybdenum-99, Neodymium-147, Neptunium-237, Nickel-63, Niobium-95, Osmium-185+191, Palladium-103, Platinum-195m, Praseodymium-143, Promethium-147, Protactinium-233, Radium-226, Rhenium-186, Rhenium-188, Rubidium-86, Ruthenium-103, Ruthenium-106, Scandium-44, Scandium-46, Selenium-75, Silver-110m, Silver-111, Sodium-22, Strontium-85, Strontium-89, Strontium-90, Sulfur-35, Tantalum-182, Technetium-99m, Tellurium-125, Tellurium-132, Thallium-204, Thorium-228, Thorium-232, Thallium-170, Tin-113, Tin-114, Tin-117m, Titanium-44, Tungsten-185, Vanadium-48, Vanadium-49, Ytterbium-169, Yttrium-86, Yttrium-88, Yttrium-90, Yttrium-91, Zinc-65, and Zirconium-95. In certain embodiments, the radionuclide is Gallium-68, Copper-64 or Yttrium-90 (paragraph 0157-8).
The phrase “therapeutically effective amount” means an amount of a compound of the present invention that (i) treats the particular disease, condition, or disorder, (ii) attenuates, ameliorates, or eliminates one or more symptoms of the particular disease, condition, or disorder, or (iii) prevents or delays the onset of one or more symptoms of the particular disease, condition, or disorder described herein. In the case of cancer, the therapeutically effective amount of the drug may reduce the number of cancer cells; reduce the tumor size; inhibit (i.e., slow to some extent and preferably stop) cancer cell infiltration into peripheral organs; inhibit (i.e., slow to some extent and preferably stop) tumor metastasis; inhibit, to some extent, tumor growth; and/or relieve to some extent one or more of the symptoms associated with the cancer. To the extent the drug may prevent growth and/or kill existing cancer cells, it may be cytostatic and/or cytotoxic. For cancer therapy, efficacy can be measured, for example, by assessing the time to disease progression (TTP) and/or determining the response rate (RR).
Cancers include carcinoma…, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, anal carcinoma, penile carcinoma, head and neck cancer, and melanoma.
GRP78 is a 78 kDa molecular chaperone that resides primarily in the endoplasmic reticulum however emerging evidences have shown translocation of GRP78 on the cell surface in the tumor microenvironment (Amy. S. Lee Cancer Res (2007); 77:3496-3499). As described herein the potential of GRP78 targeted peptides for molecular imaging and targeted radionuclide therapy were evaluated. Two sets of GRP78 targeted peptides were synthesized. The PEP42 analogues (N-DOTA/flourescein-PEP42 and Lys-DOTA/flourescein-PEP42) are 13-mer cyclized peptides in which the position of DOTA was varied (paragraph 0238).
Kapoor does not specifically teach that the prostate cancer is castration resistant prostate cancer or resistant to enzlutamide.
Enriquez teaches that fatal neuroendocrine differentiation (NED) of castration resistant prostate cancer is a recurrent mechanism of resistance to androgen deprivation therapies (ADT) and antiandrogen receptor pathway inhibitors (ARPI) in patients. The design of effective therapies for neuroendocrine prostate cancer (NEPC) is complicated by limited knowledge of the molecular mechanisms governing NED. The paucity of acquired genomic alterations and the deregulation of epigenetic and transcription factors suggest a potential contribution from the microenvironment. In this context, whether ADT/ARPI induces stromal cells to release NED-promoting molecules and the underlying molecular networks are unestablished. Here, we utilized transgenic and transplantable mouse models and coculture experiments to unveil a novel tumor-stroma cross-talk that is able to induce NED under the pressure of androgen deprivation. Castration induced upregulation of GRP78 in tumor cells, which triggers miR29-b–mediated downregulation of the matricellular protein SPARC in the nearby stroma. SPARC downregulation enabled stromal cells to release IL6, a known inducer of NED. A drug that targets GRP78 blocked NED in castrated mice. A public, human NEPC gene expression dataset showed that Hspa5 (encoding forGRP78) positively correlates with hallmarks of NED. Finally, prostate cancer specimens from patients developing local NED after ADT showed GRP78 upregulation in tumor cells and SPARC downregulation in the stroma. These results point to GRP78 as a potential therapeutic target and to SPARC downregulation in stromal cells as a potential early biomarker of tumors undergoing NED (abstract).
Prostate cancer is the second leading cause of cancer-related death and the most commonly diagnosed cancer in the U.S. males. Being a hormone-driven disease, advanced and metastatic tumors are treated with androgen deprivation therapy (ADT). However, this treatment eventually leads to castration-resistant prostate cancer (CRPC) in most patients. Despite the introduction of next-generation ADT such as enzalutamide or abiraterone, which blocks the androgen receptor (AR) pathway (named “androgen receptor pathway inhibitors”, or ARPI), prognosis remains dismal because of primary or acquired resistance. Therapeutic resistance of CRPC is often associated with the gain of neuroendocrine (NE) feature.
Here, we unveil that a cross-talk between tumor and stromal cells is necessary for adenocarcinoma–NEPC transition under the pressure of ADT. In response to therapy, tumor cells release miR29-b, which in turn triggers the downregulation of SPARC in stromal cells. We demonstrate that stromal SPARC downregulation is a key event needed for NED of prostate cancer cells, and could represent a potential biomarker. We also prove that pharmacologic inhibition of GRP78, the driver of this cross-talk, restrains NED in castrated TRAMP mice, highlighting GRP78 as a promoter of NED and a potential therapeutic target in patients (page 4258).
It would have been obvious to one of ordinary skill in the art at the time of the invention to provide the radiolabeled GRP78 targeting compositions taught by Kapoor for castration-resistant and/or enzalutamide resistant prostate cancer as the type of prostate cancer which is treated by the compositions when the teaching of Kapoor is taken in view of Enriquez. One would have been motivated to do so, with a reasonable expectation of success, because Enriquez teaches that castration-resistant and/or enzalutamide resistant prostate cancer because Enriquez teaches GRP78 as a potential therapeutic target in prostate cancer patients, as GRP78 is shown to be a promoter of NED and a potential therapeutic target in patients, as NED of castration resistant prostate cancer is a recurrent mechanism of resistance to androgen deprivation therapies (ADT) and antiandrogen receptor pathway inhibitors (ARPI) in patients.
With regard to the limitation wherein the GRP78-binding agent induces endoplasmic reticulum stress and activates deoxyribonucleic acid damage response in a cancerous tissue including cell-surface GRP78 in the subject and the prostate tumor expresses p53 and the labeled GRP-binding agent induces apoptotic cell death, it is noted that “Products of identical chemical composition cannot have mutually exclusive properties.” A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure or composition as that which is claimed, the properties applicant discloses and/or claims are necessarily present. See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). The “discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” See Atlas Power Co. v. Ireco Inc., 51 USPQ 2d 1943, 1947 (Fed. Cir. 1999). Therefore, merely claiming a new use, new function, or new property, which is inherently present in the prior art does not make the claim patentable. See In re Best, 195 USPQ 430, 433 (CCPA 1977), and MPEP § 2112.
Conclusion
No claims are allowed at this time.
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/LHS/
/JAKE M VU/Primary Examiner, Art Unit 1618
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