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 .
Status of Claims
Examined Herein: 1-25
Priority
Priority to PRO 63/518,272 filed on 8/8/2023, PRO 63/588,202 filed on 10/5/2023, PRO 63/621,965 filed on 1/17/2024, and PRO 63/626,838 filed on 1/30/2024 is acknowledged.
Drawings
The drawings filed on 8/8/2024 are accepted.
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.
Claims 1-7 and 10-16 are rejected under 35 U.S.C. 103 as being unpatentable over Cantiello (Comparison Between 64Cu-PSMA-617 PET/CT and 18F-Choline PET/CT Imaging in Early Diagnosis of Prostate Cancer Biochemical Recurrence, 2018, Clinical Genitourinary Cancer, Volume 16, Issue 5), in view of Lee (The Feasibility of 64Cu-PSMA I&T PET for Prostate Cancers, 7/29/2022, Cancer Biotherapy and Radiopharmaceuticals, Vol. 37, No. 6).
With respect to claim 1, 2, 4, and 7, Cantiello discloses a method of detecting prostate cancer in a human patient in need thereof, comprising the steps of:
(a) administering to the patient about 7 mCi (260 MBq) to about 10 mCi (370 MBq) of a 64Cu-PSMA-617 composition, and
(b) imaging the patient about 1 hour and 4 hours post administration of the composition,
wherein the image is of acceptable image quality. [Cantiello, Page 386, Col. 2, Paragraph 3-4]
With respect to claim 3, Cantiello discloses the patient is imaged using positron emission tomography. [Cantiello, Page 386, Col. 2, Paragraph 3-4]
With respect to claim 5, Cantiello discloses the patient is imaged at about 1 hour and 4 hours post administration of the composition. [Cantiello, Page 386, Col. 2, Paragraph 3-4] The specification discloses the term "about" broadens a particular numerical value by at least +/- 10%. [Specification, 0031] In light of the specification, the limitations of claim 5 are interpreted as the patient is imaged any time at or before 108 minutes or at or beyond 132 minutes. 1 hour is a time before 108 minutes and 4 hours is a time beyond 132 minutes, therefore Cantiello discloses the patient is imaged at “about” 2 hours post administration of the composition.
With respect to claim 6, Cantiello discloses the patient is imaged at about 1 hour and 4 hours post administration of the composition. [Cantiello, Page 386, Col. 2, Paragraph 3-4] The specification discloses the term "about" broadens a particular numerical value by at least +/- 10%. [Specification, 0031] In light of the specification, the limitations of claim 6 are interpreted as the patient is imaged any time at or before 162 minutes or at or beyond 198 minutes. 1 hour is a time before 162 minutes and 4 hours is a time beyond 198 minutes, therefore Cantiello discloses the patient is imaged at “about” 3 hours post administration of the composition.
With respect to claim 10, 11, 13, and 16, Cantiello discloses a method of detecting prostate cancer in a human patient in need thereof, comprising the steps of:
(a) administering to the patient about 7 mCi (260 MBq) to about 10 mCi (370 MBq) of a 64Cu-PSMA-617 composition, and
(b) imaging the patient 1 hour and 4 hours after administration of the composition;
wherein the resulting image allows a reader to detect prostate cancer in the patient. [Cantiello, Page 386, Col. 2, Paragraph 3-4]
With respect to claim 12, Cantiello discloses the patient is imaged using positron emission tomography. [Cantiello, Page 386, Col. 2, Paragraph 3-4]
With respect to claim 14, Cantiello discloses the patient is imaged at about 1 hour and 4 hours post administration of the composition. [Cantiello, Page 386, Col. 2, Paragraph 3-4] The specification discloses the term "about" broadens a particular numerical value by at least +/- 10%. [Specification, 0031] In light of the specification, the limitations of claim 14 are interpreted as the patient is imaged any time at or before 108 minutes or at or beyond 132 minutes. 1 hour is a time before 108 minutes and 4 hours is a time beyond 132 minutes, therefore Cantiello discloses the patient is imaged at “about” 2 hours post administration of the composition.
With respect to claim 15, Cantiello discloses the patient is imaged at about 1 hour and 4 hours post administration of the composition. [Cantiello, Page 386, Col. 2, Paragraph 3-4] The specification discloses the term "about" broadens a particular numerical value by at least +/- 10%. [Specification, 0031] In light of the specification, the limitations of claim 15 are interpreted as the patient is imaged any time at or before 162 minutes or at or beyond 198 minutes. 1 hour is a time before 162 minutes and 4 hours is a time beyond 198 minutes, therefore Cantiello discloses the patient is imaged at “about” 3 hours post administration of the composition.
Cantiello does not disclose the composition administered is 64Cu-PSMA I&T.
However, with respect to claim 1 and 10, Lee discloses a composition, 64Cu-PSMA I& T. Lee further discloses although 64Cu-PSMA-617 can show high diagnostic accuracy and perform better than 18F-choline in the case of low PSA values, it is not readily available. Therefore, a need arises for other PSMA inhibitors suitable for Cu-64 labeling. Lee discloses PSMA I&T is a good candidate for Cu-64 labeling because of its chemical structure. Specifically, the DOTAGA chelator of PSMA I&T has been reported to improve ligand pharmacokinetics and play a crucial role in high affinity on the basis of high tumor accumulation. Also, DOTAGA chelator show a much lower clearance than other chelators such as NOTA and NODAGA. Lee concludes that PSMA I&T is suitable for labeling with Cu-64 and discloses 64Cu-PSMA-I&T might be considered as a candidate of future clinical trials. [Lee, Page 418, Col. 1, Paragraph 1-3]
Modifying the method disclosed by Cantiello by replacing 64Cu-PSMA-617 with 64Cu-PSMA-I&T results in the method of claim 1 and 10.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Cantiello by replacing 64Cu-PSMA-617 with 64Cu-PSMA-I&T and have a reasonable expectation of success. Cantiello discloses a method of detecting prostate cancer in a human patient comprising administering a 64Cu-PSMA-617 composition to the patient and imagining the patient via PET. Lee discloses 64Cu-PSMA-617 shows high diagnostic accuracy and performs better than 18F-choline in the case of low PSA values, but it is not readily available. As a result, a need arises for other PSMA inhibitors suitable for Cu-64 labeling. Lee discloses PSMA I&T is suitable for Cu-64 labeling because of its chemical structure. The DOTAGA chelator of PSMA I&T has been reported to improve ligand pharmacokinetics, show a much lower clearance than other chelators, and play a crucial role in high affinity on the basis of high tumor accumulation. Thus, Lee establishes 64Cu-PSMA-I&T is a viable and superior alternative to 64Cu-PSMA-617. Accordingly, the combined teachings of Cantiello and Lee suggest that the method disclosed by Cantiello may be carried out with 64Cu-PSMA-I&T. Therefore, it is reasonable to expect the method disclosed by Cantiello may be modified by replacing 64Cu-PSMA-617 with 64Cu-PSMA-I&T. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Lee discloses 64Cu-PSMA-617 is not readily available, which creates a need arises for other PSMA inhibitors for 64Cu labeling. Accordingly, 64Cu-PSMA-I&T fulfills this need, as PSMA I&T is an especially good candidate for 64Cu labeling because of its chemical structure. The DOTAGA chelator of PSMA I&T improves ligand pharmacokinetics, shows much lower clearance than other chelators such as NOTA and NODAGA, and plays a crucial role in high affinity on the basis of high tumor accumulation. [Lee, Page 418, Col. 1, Paragraph 1-3] Therefore, one would have been motivated by the expectation that the aforementioned modification would yield a 64Cu labelled PSMA inhibitor that improves ligand pharmokinetics, exhibits a lower clearance than other chelators, and influences tumor accumulation, thereby satisfying a need in the art.
Claims 1-18 are rejected under 35 U.S.C. 103 as being unpatentable over Cantiello and Lee, as applied to claim 1-7 and 10-16 above, and further in view of Piccardo (64CuCl2 PET/CT in Prostate Cancer Relapse, 2018, The Journal of Nuclear Medicine, Vol. 59, No. 3).
With respect to claim 1 and 10, Cantiello and Lee disclose the teachings above.
With respect to claim 8 and 9, Cantiello discloses the correct detection rate is greater than 60%. [Cantiello, Page 388, Table 3]
With respect to claim 17 and 18, Cantiello discloses the correct detection rate is greater than 60%. [Cantiello, Page 388, Table 3]
Cantiello and Lee do not disclose the correct detection rate is verified by histopathology or a separate, confirmatory imaging modality.
However, with respect to claim 8, 9, 17, and 18, Piccardo discloses a method of detecting prostate cancer in a human patient in need thereof, comprising the steps of: (a) administering to the patient about 5 mCi (200 MBq) – 7 mCi (250 MBq) of a Cu-64 composition, and (b) imaging the patient using positron emission tomography. [Piccardo, Abstract, Page 445, Col. 2, Paragraph 1 and 3 and Figure 1] Piccardo discloses the correct detection rate is greater than 60%, as verified by histopathology and separate confirmatory imaging modalities, including mpMRI, 18F-choline PET/CT, and salvage EBRT. [Piccardo, Page 447, Figure 2 and Col. 2, Paragraph 5]
Modifying the method disclosed by Cantiello and Lee by verifying the correct detection rate by histopathology or a separate confirmatory imaging modality, results in the method of claim 8, 9, 17, and 18.
It would be obvious to one of ordinary skill in the art to further modify the method disclosed by Cantiello and Lee by verifying the correct detection rate by histopathology or a separate confirmatory imaging modality and have a reasonable expectation of success. Cantiello and Lee disclose a method of detecting prostate cancer in a human patient comprising administering a Cu-64 compound to the patient, imaging the patient via PET, and determining the correct detection rate. Cantiello admits the lack of histopathologic validation of the detection rate is a limitation of the method. [Cantiello, Page 389, Col. 2, Paragraph 3 – Page 390, Col. 1, Paragraph 1] Piccardo discloses a method of detecting prostate cancer in a human patient comprising administering a Cu-64 compound to the patient, imaging the patient via PET, and determining the correct detection rate. Piccardo further discloses the correct detection rate is verified by histopathology and separate confirmatory imaging modalities, including mpMRI, 18F-choline PET/CT, and salvage EBRT. Thus, Piccardo establishes that the detection rate in a method of detecting prostate cancer in a human patient may be verified by histopathology and separate confirmatory imaging modalities, including mpMRI, 18F-choline PET/CT, and salvage EBRT. Accordingly, the combined teachings of Cantiello, Lee, and Piccardo suggest that the correct detection rate in the method disclosed by Cantiello may be verified by histopathology and separate confirmatory imaging modalities, including mpMRI, 18F-choline PET/CT, and salvage EBRT. Therefore, it is reasonable to expect the method disclosed by Cantiello and Lee may be modified by verifying the correct detection rate by histopathology or a separate confirmatory imaging modality. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Piccardo discloses histopathology and other separate confirmatory imaging modalities provide confirmation of the site of disease. [Piccardo, Page 447, Figure 2 and Col. 2, Paragraph 5] Therefore, one would have been motivated by the expectation that the aforementioned modification would provide confirmation of the site of disease in the method disclosed by Cantiello and Lee.
Claims 19-25 are rejected under 35 U.S.C. 103 as being unpatentable over Cantiello, in view of Lee and Piccardo.
With respect to claim 19, 20, 22, and 25, Cantiello discloses a method of detecting prostate cancer in a human patient in need thereof, comprising the steps of:
(a) administering to the patient about 7 mCi (260 MBq) to about 10 mCi (370 MBq) of a Cu-64 PSMA-617 composition, and
(b) imaging the patient between about 1 hour and 4 hours post administration of the composition, wherein the resulting image does not produce a correct detection rate below 80%. [Cantiello, Page 386, Col. 2, Paragraph 3-4, Page 388, Table 3]
With respect to claim 21, Cantiello discloses the patient is imaged using positron emission tomography. [Cantiello, Page 386, Col. 2, Paragraph 3-4]
With respect to claim 23, Cantiello discloses the patient is imaged at about 1 hour and 4 hours post administration of the composition. [Cantiello, Page 386, Col. 2, Paragraph 3-4] The specification discloses the term "about" broadens a particular numerical value by at least +/- 10%. [Specification, 0031] In light of the specification, the limitations of claim 23 are interpreted as the patient is imaged any time at or before 108 minutes or at or beyond 132 minutes. 1 hour is a time before 108 minutes and 4 hours is a time beyond 132 minutes, therefore Cantiello discloses the patient is imaged at “about” 2 hours post administration of the composition.
With respect to claim 24, Cantiello discloses the patient is imaged at about 1 hour and 4 hours post administration of the composition. [Cantiello, Page 386, Col. 2, Paragraph 3-4] The specification discloses the term "about" broadens a particular numerical value by at least +/- 10%. [Specification, 0031] In light of the specification, the limitations of claim 24 are interpreted as the patient is imaged any time at or before 162 minutes or at or beyond 198 minutes. 1 hour is a time before 162 minutes and 4 hours is a time beyond 198 minutes, therefore Cantiello discloses the patient is imaged at “about” 3 hours post administration of the composition.
Cantiello does not disclose the composition administered is Cu-64 PSMA I&T or the correct detection rate is verified by histopathology or a separate, confirmatory imaging modality.
However, with respect to claim 19, Lee discloses a composition, 64Cu-PSMA-I&T. Lee further discloses although 64Cu-PSMA-617 can show high diagnostic accuracy and perform better than 18F-choline in the case of low PSA values, it is not readily available. Therefore, a need arises for other PSMA inhibitors suitable for Cu-64 labeling. Lee discloses PSMA I&T is a good candidate for Cu-64 labeling because of its chemical structure. Specifically, the DOTAGA chelator of PSMA I&T has been reported to improve ligand pharmacokinetics and play a crucial role in high affinity on the basis of high tumor accumulation. Also, DOTAGA chelator show a much lower clearance than other chelators such as NOTA and NODAGA. Lee concludes that PSMA I&T is suitable for labeling with Cu-64 and discloses 64Cu-PSMA-I&T might be considered as a candidate of future clinical trials. [Lee, Page 418, Col. 1, Paragraph 1-3]
Cantiello and Lee do not disclose the correct detection rate is verified by histopathology or a separate, confirmatory imaging modality.
However, with respect to claim 19, Piccardo discloses a method of detecting prostate cancer in a human patient in need thereof, comprising the steps of: (a) administering to the patient about 5 mCi (200 MBq) – 7 mCi (250 MBq) of a Cu-64 composition, and (b) imaging the patient using positron emission tomography. [Piccardo, Abstract, Page 445, Col. 2, Paragraph 1 and 3 and Figure 1] Piccardo discloses the correct detection rate is greater than 60%, as verified by histopathology and separate confirmatory imaging modalities, including mpMRI, 18F-choline PET/CT, and salvage EBRT. [Piccardo, Page 447, Figure 2 and Col. 2, Paragraph 5]
Modifying the method disclosed by Cantiello by replacing 64Cu-PSMA-617 with 64Cu-PSMA-I&T and by verifying the correct detection rate by histopathology or a separate confirmatory imaging modality, results in the method of claim 19.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Cantiello by replacing 64Cu-PSMA-617 with 64Cu-PSMA-I&T and have a reasonable expectation of success. Cantiello discloses a method of detecting prostate cancer in a human patient comprising administering a 64Cu-PSMA-617 composition to the patient and imagining the patient via PET. Lee discloses 64Cu-PSMA-617 shows high diagnostic accuracy and performs better than 18F-choline in the case of low PSA values, but it is not readily available. As a result, a need arises for other PSMA inhibitors suitable for Cu-64 labeling. Lee discloses PSMA I&T is suitable for Cu-64 labeling because of its chemical structure. The DOTAGA chelator of PSMA I&T has been reported to improve ligand pharmacokinetics, show a much lower clearance than other chelators, and play a crucial role in high affinity on the basis of high tumor accumulation. Thus, Lee establishes 64Cu-PSMA-I&T is a viable and superior alternative to 64Cu-PSMA-617. Accordingly, the combined teachings of Cantiello and Lee suggest that the method disclosed by Cantiello may be carried out with 64Cu-PSMA-I&T. Therefore, it is reasonable to expect the method disclosed by Cantiello may be modified by replacing 64Cu-PSMA-617 with 64Cu-PSMA-I&T. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Lee discloses 64Cu-PSMA-617 is not readily available, which creates a need arises for other PSMA inhibitors for 64Cu labeling. Accordingly, 64Cu-PSMA-I&T fulfills this need, as PSMA I&T is an especially good candidate for 64Cu labeling because of its chemical structure. The DOTAGA chelator of PSMA I&T improves ligand pharmacokinetics, shows much lower clearance than other chelators such as NOTA and NODAGA, and plays a crucial role in high affinity on the basis of high tumor accumulation. [Lee, Page 418, Col. 1, Paragraph 1-3] Therefore, one would have been motivated by the expectation that the aforementioned modification would yield a 64Cu labelled PSMA inhibitor that improves ligand pharmokinetics, exhibits a lower clearance than other chelators, and influences tumor accumulation, thereby satisfying a need in the art.
It would be obvious to one of ordinary skill in the art to further modify the method disclosed by Cantiello and Lee by verifying the correct detection rate by histopathology or a separate confirmatory imaging modality and have a reasonable expectation of success. Cantiello and Lee disclose a method of detecting prostate cancer in a human patient comprising administering a Cu-64 compound to the patient, imaging the patient via PET, and determining the correct detection rate. Cantiello admits the lack of histopathologic validation of the detection rate is a limitation of the method. [Cantiello, Page 389, Col. 2, Paragraph 3 – Page 390, Col. 1, Paragraph 1] Piccardo discloses a method of detecting prostate cancer in a human patient comprising administering a Cu-64 compound to the patient, imaging the patient via PET, and determining the correct detection rate. Piccardo further discloses the correct detection rate is verified by histopathology and separate confirmatory imaging modalities, including mpMRI, 18F-choline PET/CT, and salvage EBRT. Thus, Piccardo establishes that the detection rate in a method of detecting prostate cancer in a human patient may be verified by histopathology and separate confirmatory imaging modalities, including mpMRI, 18F-choline PET/CT, and salvage EBRT. Accordingly, the combined teachings of Cantiello, Lee, and Piccardo suggest that the correct detection rate in the method disclosed by Cantiello may be verified by histopathology and separate confirmatory imaging modalities, including mpMRI, 18F-choline PET/CT, and salvage EBRT. Therefore, it is reasonable to expect the method disclosed by Cantiello and Lee may be modified by verifying the correct detection rate by histopathology or a separate confirmatory imaging modality. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Piccardo discloses histopathology and other separate confirmatory imaging modalities provide confirmation of the site of disease. [Piccardo, Page 447, Figure 2 and Col. 2, Paragraph 5] Therefore, one would have been motivated by the expectation that the aforementioned modification would provide confirmation of the site of disease in the method disclosed by Cantiello and Lee.
Claims 1-7 and 10-16 are rejected under 35 U.S.C. 103 as being unpatentable over Ozulker (Efficacy of early imaging with 68Ga-PSMA I&T in the discrimination of pelvic lesions in prostate cancer patients, 9/6/2018, Revista Española de Medicina Nuclear e Imagen Molecular (English Edition), Volume 38, Issue 2), in view of Lee and Piccardo,
With respect to claim 1 and 4, Ozulker discloses a method of detecting prostate cancer in a human patient in need thereof, comprising the steps of:
(a) administering to the patient a Ga-68 PSMA I&T composition, and
(b) imaging the patient 1 hour post administration of the composition;
wherein the image is of acceptable image quality. [Ozulker, Page 102, Col. 1, Paragraph 1-2 and Page 103 Figure 1]
With respect to claim 3, Ozulker discloses the patient is imaged using positron emission tomography. [Ozulker, Page 102, Col. 1, Paragraph 1-2 and Page 103 Figure 1]
With respect to claim 5, Ozulker discloses the patient is imaged at 1 hour post administration of the composition. [Ozulker, Page 102, Col. 1, Paragraph 1] The specification discloses the term "about" broadens a particular numerical value by at least +/- 10%. [Specification, 0031] In light of the specification, the limitations of claim 5 are interpreted as the patient is imaged any time at or before 108 minutes or at or beyond 132 minutes. 1 hour is a time before 108 minutes, therefore Ozulker discloses the patient is imaged at “about” 2 hours post administration of the composition.
With respect to claim 6, Ozulker discloses the patient is imaged at 1 hour post administration of the composition. [Ozulker, Page 102, Col. 1, Paragraph 1] The specification discloses the term "about" broadens a particular numerical value by at least +/- 10%. [Specification, 0031] In light of the specification, the limitations of claim 6 are interpreted as the patient is imaged any time at or before 162 minutes or at or beyond 198 minutes. 1 hour is a time before 162 minutes, therefore Ozulker discloses the patient is imaged at “about” 3 hours post administration of the composition.
With respect to claim 7, Ozulker discloses the patient is imaged at 1 hour post administration of the composition. [Ozulker, Page 102, Col. 1, Paragraph 1] The specification discloses the term "about" broadens a particular numerical value by at least +/- 10%. [Specification, 0031] In light of the specification, the limitations of claim 7 are interpreted as the patient is imaged any time at or before 216 minutes or at or beyond 282 minutes. 1 hour is a time before 216 minutes, therefore Ozulker discloses the patient is imaged at “about” 4 hours post administration of the composition.
With respect to claim 10 and 13, Ozulker discloses a method of detecting prostate cancer in a human patient in need thereof, comprising the steps of:
(a) administering to the patient a Ga-68 PSMA I&T composition, and
(b) imaging the patient 1 hour after administration of the composition;
wherein the resulting image allows a reader to detect prostate cancer in the patient. [Ozulker, Page 102, Col. 1, Paragraph 1-2 and Page 103 Figure 1]
With respect to claim 12, Ozulker discloses the patient is imaged using positron emission tomography. [Ozulker, Page 102, Col. 1, Paragraph 1-2 and Page 103 Figure 1]
With respect to claim 14, Ozulker discloses the patient is imaged at 1 hour post administration of the composition. [Ozulker, Page 102, Col. 1, Paragraph 1] The specification discloses the term "about" broadens a particular numerical value by at least +/- 10%. [Specification, 0031] In light of the specification, the limitations of claim 14 are interpreted as the patient is imaged any time at or before 108 minutes or at or beyond 132 minutes. 1 hour is a time before 108 minutes, therefore Ozulker discloses the patient is imaged at “about” 2 hours post administration of the composition.
With respect to claim 15, Ozulker discloses the patient is imaged at 1 hour post administration of the composition. [Ozulker, Page 102, Col. 1, Paragraph 1] The specification discloses the term "about" broadens a particular numerical value by at least +/- 10%. [Specification, 0031] In light of the specification, the limitations of claim 15 are interpreted as the patient is imaged any time at or before 162 minutes or at or beyond 198 minutes. 1 hour is a time before 162 minutes, therefore Ozulker discloses the patient is imaged at “about” 3 hours post administration of the composition.
With respect to claim 16, Ozulker discloses the patient is imaged at 1 hour post administration of the composition. [Ozulker, Page 102, Col. 1, Paragraph 1] The specification discloses the term "about" broadens a particular numerical value by at least +/- 10%. [Specification, 0031] In light of the specification, the limitations of claim 16 are interpreted as the patient is imaged any time at or before 216 minutes or at or beyond 282 minutes. 1 hour is a time before 216 minutes, therefore Ozulker discloses the patient is imaged at “about” 4 hours post administration of the composition.
Furthermore, Ozulker discloses PSMA-I&T is capable of being labeled with various radionuclides including 177Lu and 111In and studies on these theranostic agents have been conducted. [Ozulker, Page 104, Col. 2, Paragraph 2]
Cantiello does not disclose 5 mCi to about 9 mCi of a Cu-64 PSMA I&T composition is administered to the patient.
However, with respect to claim 1 and 10, Lee discloses a composition Cu-64 PSMA I&T. Lee discloses PET imaging using Cu-64 is more promising than Ga-68 because of Cu-64’s relatively long half-life (12.7 h) and economic production by cyclotron. In addition, Cu-64 reveals higher image resolution than Ga-68 due to lower energy at emission. Lee further discloses PSMA I&T is a good candidate for Cu-64 labeling, and more suitable for labeling than Ga-68, due to its relatively long half-life. [Lee, Page 418, Col. 1, Paragraph 1-3]
Furthermore, with respect to claim 1 and 10, Piccardo discloses a method of detecting prostate cancer in a human patient in need thereof, comprising the steps of: (a) administering to the patient about 5 mCi (200 MBq) – 7 mCi (250 MBq) of a Cu-64 composition, and (b) imaging the patient using positron emission tomography between about 1 hour, 4 hours, and 24 hours post administration of the composition.
Modifying the method disclosed by Ozulker by replacing 68Ga-PSMA I&T with 64Cu-PSMA I&T and administering 5 mCi to 7 mCi thereof to the patient, results in the method of claim 1 and 10.
With respect to claim 2 and 11, the combined teachings of Ozulker, Lee, and Piccardo teach that the patient is administered 5 mCi to 7 mCi of the Cu-64 PSMA I&T composition. The specification discloses the term "about" broadens a particular numerical value by at least +/- 10%. [Specification, 0031] In light of the specification, the limitations of claim 2 and 11 are interpreted as the patient is administered less than or equal to 7.2 mCi or greater than or equal to 8.8 mCi. 5 mCi to 7 mCi is less than 7.2 mCi, therefore Ozulker, Lee, and Piccardo teach that the patient is administered “about” 8 mCi of the 64Cu-PSMA I&T composition.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Ozulker by replacing 68Ga-PSMA I&T with 64Cu-PSMA I&T and have a reasonable expectation of success. Ozulker discloses a method of detecting prostate cancer in a human patient comprising administering to the patient a Ga-68 PSMA I&T composition and imaging the patient using PET. Ozulker further discloses PSMA-I&T is capable of being labeled with various radionuclides including 177Lu and 111In. Lee discloses PET imaging using Cu-64 is promising rather than Ga-64 because of Cu-64’s relatively long half-life (12.7 h) and economic production by cyclotron. In addition, Cu-64 reveals higher image resolution than Ga-68 due to lower energy at emission. As a result, Lee discloses PSMA I&T labelled with Cu-64 is more suitable than Ga-68 due to its relatively long half-life. Thus, Lee establishes that PSMA I&T may be labelled with various radionuclides known in the art, including 64Cu and 68Ga, and that 64Cu is more suitable to label PSMA I&T than 68Ga because it has a longer half-life and higher image resolution. Thus, the combined teachings of Ozulker suggest that the PSMA I&T composition disclosed by Ozulker may be labeled with 64Cu rather than 68Ga. Therefore, it is reasonable to expect the method disclosed by Ozulker may be modified by replacing 68Ga-PSMA I&T with 64Cu-PSMA I&T. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Lee discloses PET imaging using Cu-64 is more promising than Ga-68 because of its relatively long half-life (12.7 h), economic production by cyclotron, and ability to reveal higher image resolution compared to 68Ga. [Lee, Page 418, Col. 1, Paragraph 1-3] Therefore, one would be motivated by the expectation that the aforementioned modification would improve PET imaging in the method disclosed by Ozulker by revealing a higher image resolution.
It would be obvious to one of ordinary skill in the art to further modify the method disclosed by Ozulker and Lee by administering 5 mCi to 7 mCi of Cu-64 PSMA I&T to the patient and have a reasonable expectation of success. Ozulker and Lee disclose a method of detecting prostate cancer in a human patient, comprising administering to the patient a Cu-64 composition, 64Cu-PSMA I&T and imaging the patient via PET 1 hour after administration. Piccardo discloses a method of detecting prostate cancer in a human patient comprising administering to the patient about 5 mCi - 7 mCi of a Cu-64 composition, 64CuCl2, and imaging the patient using PET 1 hour after administration. Thus, Ozulker and Lee disclose a method comprising administering a Cu-64 composition to a human patient, and Piccardo establishes that 5 mCi – 7 mCi of Cu-64 is a safe and effective amount to administer in such a method. Thus, the combined teachings of Ozulker, Lee, and Piccardo suggest that 5 mCi to 7 mCi of the Cu-64 composition may be administered to the patient in the method disclosed by Ozulker and Lee. Therefore, it is reasonable to expect the method disclosed by Ozulker and Lee may be modified by administering 5 mCi to 7 mCi of 64Cu-PSMA I&T to the patient. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Piccardo discloses 5 mCi to 7 mCi is an effective activity to administer to a human patient in order to obtain quality PET scans. [Piccardo, Page 445, Col. 2, Paragraph 1 and Figure 1] Therefore, one would have been motivated by the expectation that the aforementioned modification would enable quality PET scans to be obtained in the method disclosed by Ozulker.
Response to Arguments
Applicant's arguments filed 3/24/2026 have been fully considered but they are not persuasive.
Applicant asserts “One cannot simply assume that because PSMA-617 works in humans (Cantiello), and PSMA I&T works in mice (Lee), that Cu-64 PSMA I&T will successfully image human prostate cancer with the specific dosage and timing limitations claimed.” [Remarks 3/24/2026, Page 7, Paragraph 3]
Testing in an animal model will almost invariably be sufficient to establish therapeutic or pharmacological utility for a compound, composition or process. MPEP 2107.03. Thus, a POSITA would reasonably expect Cu-64 PSMA I&T to exhibit imaging utility in a human patient based on the teachings of Lee.
Applicant asserts “The Examiner argues that Lee provides the motivation to switch to Cu-64 PSMA I&T. However, Lee explicitly states that the advantage of Cu-64 over Ga-68 is the longer half-life which allows for delayed imaging. Lee focuses on using Cu-64 PSMA I&T as a surrogate to simulate the distribution of Ac-225 for therapy dosimetry, stating: "Therefore, the authors expect to use 64Cu-PSMA I&T to calculate the dosimetry of 225Ac-PSMA I&T." [Remarks 3/24/2026, Page 8, Paragraph 1-2]
The prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed. MPEP 2143.01(VI). The instant rejection does not rely on Lee for the claimed imaging window. Such limitations are sufficiently taught by Cantiello. Lee’s disclosure does not constitute teaching away because it does not criticize, discredit, or otherwise discourage the imaging window disclosed by Cantiello. Accordingly, Lee’s disclosure does not constitute teaching way.
Applicant asserts “When so many factors driving image quality and CDR have been changed, it is inappropriate to assume that a POSITA would automatically conclude that swapping Cu-64 PSMA I&T for 64CuCl2 would be an obvious change to make and yield the same, if not better results.” [Remarks 3/24/2026, Page 9, Paragraph 3-4]
The instant rejection does not swap Cu-64 PSMA I&T for 64CuCl2 or rely on any teaching that doing so would yield the same, if not better results. Rather, the instant rejection relies on Piccardo to establish that a POSITA would be motivated to modify the method disclosed by Cantiello by verifying the correct detection rate via histopathology or a separate, confirmatory imaging modality, and have a reasonable expectation of success. Conclusive proof of efficacy is not required to show a reasonable expectation of success. MPEP 2143.02.
Applicant asserts “The references are non-analogous in mechanism and biodistribution profile regarding the critical limitation of pelvic lesion detection and verification.” [Remarks 3/24/2026, Page 10, Paragraph 1]
A reference is analogous art to the claimed invention if: (1) the reference is from the same field of endeavor as the claimed invention (even if it addresses a different problem); or (2) the reference is reasonably pertinent to the problem faced by the inventor (even if it is not in the same field of endeavor as the claimed invention). MPEP 2141.01(a). A reference need not be analogous in mechanism and biodistribution profile to be considered analogous art.
Applicant asserts “The Examiner appears to rely on specific subgroups within Cantiello (e.g., PSA > 1.51 ng/mL) to find a rate higher than 80%. However, claim 19 is not limited to a high-PSA subgroup; it claims the method of detecting prostate cancer in a human patient generally. The prior art (Cantiello) explicitly teaches that for the general population of patients, the detection rate is 74.4%, thus, failing to meet the claim limitation.” [Remarks 3/24/2026, Page 10, Paragraph 2-3]
Applicant alleges that Cantiello fails to teach a limitation that is not recited in the instant claims. The claim limitation does not exclude the high-PSA subgroup cited by the Examiner, nor is the claim limited to a general population of patients that excludes such subgroups.
Applicant asserts “There is no motivation for a skilled artisan to switch from Ga-68 (ideal for 1h imaging) to Cu-64 (ideal for 24 hour imaging, as taught by Lee) if they intend to image at 1-4 hours as claimed. In fact, switching to Cu-64 for early imaging often results in a higher radiation dose to the patient without the benefit of the delayed scan for which the isotope is designed. Thus, the motivation to combine Ozulker and Lee to arrive at the specific method claimed (Cu-64 PSMA I&T imaged at 1-4 hours) is lacking.” [Remarks 3/24/2026, Page 11, Paragraph 1]
The reason or motivation to modify a reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. MPEP 2144(IV). The motivation to combine the cited references is not lacking merely because Applicant finds Ga-68 more advantageous than Cu-64. A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to other products for the same use. MPEP 2123(II).
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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