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 .
Information Disclosure Statement
The information discloser statement filed on February 4, 2026 is acknowledged and has been considered by the examiner.
The information disclosure statement filed September 24, 2024 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered. In this instance, reference WO 2021/005131 A1 has not been provided by Applicant. Accordingly, this has been lined through in the IDS.
Drawings
The drawings are objected to because of the following informalities:
Figures 54 and 55 are of low resolution and are blurry. It is difficult to interpret the labels and values on the graphs. Furthermore, it is not possible to discern which curves on the plots correspond to which concentration of ligand. Therefore, these drawings are not able to be interpreted by the examiner.
Figure 56 is of inadequate resolution. It is difficult to discern the labels and values on the axes of the plot. Therefore, the drawing is not in a state in which the examiner can interpret it.
In Figure 57, the x-axis labels of the two biodistribution plots are formatted in a way in which the characters of the labels have shifted in a way that makes them difficult to read and discern what words are written. Furthermore, in the Uptake graph, it is not possible to distinguish between the Surface Uptake and Self-block data being presented on the graph, as these look identical in the key of the graph.
Appropriate correction is required.
Claim Objections
Claims 23, 25, 28, 31, 33, and 36 are objected to because of the following informalities:
In claims 23 and 31, “the FAP-tageted conjugate” is recited. It appears this is a typographical error and should instead read as “the FAP-targeted conjugate.”
In claims 25 and 33, head and neck cancer appears in the list of cancers twice. One instance should be removed in each list.
In claims 28 and 36, both glycerol and glycerine are listed as optional components in the pharmaceutical composition. To the examiner’s understanding, glycerol and glycerine are the same molecule. Therefore, this is a duplication of items in the lists and one should be removed from each list.
In claims 28 and 36, “a synthetic solvents” appears to contain a grammatical error. The examiner suggests this phrase be amended to “a synthetic solvent” instead.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 31 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 31 recites the limitation "The method according to claim 19" in the first line. There is insufficient antecedent basis for this limitation in the claim. In the set of claims being examined, there is no claim 19, as claim 19 was canceled by the Applicant on August 10, 2026. For the purpose of examination, the examiner will interpret claim 31 to depend on claim 29 and include the limitation of the method according to claim 29 instead.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 21-22, 24-30, and 32-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30-41 of copending Application No. 18/537,730 in view of Osterkamp (EP 3,763,726 A1 – provided by applicant in IDS filed September 24, 2024).
The claims of copending Application No. 18/537,730 (henceforth referred to as the ‘730 application) are drawn to methods of using fibroblast activation protein (FAP)-targeted conjugate compounds labeled with radionuclides for imaging or treating cancer. These compounds are characterized by a structure comprising a cyclic peptide, a chelating moiety, and a linking group. The conjugates may be administered by multiple means and may be provided in various formulations.
The claims of the copending ‘730 application are not drawn to methods of using FAP targeting conjugate compounds possessing structures identical to those recited in instant claims 21 and 29)
Osterkamp teaches cyclic peptide compounds that target fibroblast activation protein (FAP) (Title and Abstract). Osterkamp teaches that such cyclic peptides can have a range of sequences (pg. 16, lines 25-55). Osterkamp teaches several examples of peptides cyclized by two cysteine residues connected by a xylene group and wherein the cyclic peptide is connected to a chelating group (which may coordinate a metal) through a linker (pg. 42-54). Osterkamp teaches that the chelator can be one of several structures, with preferable embodiments including DOTA, NOTA, and NODAGA (pg. 89-90). Osterkamp teaches that these cyclic peptides may be labeled with radionuclides (pg. 91, [0151]). Osterkamp teaches that such radioconjugates may be used for therapy and diagnostics (pg. 124, [0161]).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the methods of using FAP-targeted conjugates for imaging and treating cancer of the copending ‘730 application by modifying the FAP-targeted conjugates through the substitution of the NODAGA chelator in the last structure of conflicting claim 21 (upon which conflicting claims 30-41 depend) with the NOTA chelator group of Osterkamp, as these chelating groups perform the same function and serve the same purpose in these cyclic peptide conjugates (MPEP § 2143(I)(B)).
A person of ordinary skill in the art would have had a reasonable expectation of success in making this substitution because both the copending ‘730 application and XXX relate to FAP-targeting cyclic peptides and radionuclide labeled conjugates thereof. Furthermore, Osterkamp teaches that several chelators can be used in such conjugates, suggesting such compounds to be modular and chelating groups to be substitutable.
The skilled artisan would have been motivated to make this substitution because changing from NODAGA to NOTA effectively changes the distance between the cyclic peptide and radionuclide, which is a factor to optimize in radioconjugates.
Regarding instant claim 21, conflicting claim 30 of the copending ‘730 application is drawn to a method of imaging or diagnosing a cancer associated with overexpression of FAP in a patient, the method comprising administering a FAP-targeted conjugate wherein the conjugate is labeled with a radionuclide, and imaging the patient. Additionally, Osterkamp teaches that FAP-targeting cyclic peptide radioconjugates can contain a variety of chelating groups, including NODAGA, DOTA, and NOTA (pg. 89-90). The substitution of the NODAGA in the last structure of conflicting claim 21 with NOTA would result in a compound that reads on the first structure of instant claim 21, rendering this method obvious.
Regarding instant claim 22, the last structure of conflicting claim 21 of the copending ‘730 application is the same as the structure of instant claim 22 other than the chelator moiety. Additionally, conflicting claim 30 of the copending application is drawn to a method of using this conjugate for imaging or diagnosing a cancer. Furthermore, Osterkamp teaches FAP-targeting radioconjugates may contain NOTA as the chelator (pg. 89-90). As described above, the combination of the reference application claims and the teachings of Osterkamp render the imaging use of the compound of instant claim 22 obvious.
Regarding instant claim 24, conflicting claim 31 of the copending ‘730 application is drawn to embodiments wherein the radionuclide is selected from the group consisting of In-111, Pb-203, Cu-64, Ga-68, and Zr-89.
Regarding instant claim 25, conflicting claim 32 of the copending ‘730 application is drawn to embodiments wherein the cancer comprises any selected from the group consisting of sarcoma, head and neck cancer, esophageal cancer, glioma, cholangiocarcinoma, breast cancer, lung cancer, prostate cancer, pancreatic cancer, thymus cancer, ovarian cancer, desmoid tumor, chordoma, colorectal cancer, anal cancer, neuroendocrine tumor, small intestine cancer, medullary thyroid cancer, cervical cancer, endometrial cancer, hepatocellular cancer, gastric cancer, adenoid cystic cancer, pheochromocytoma, differentiated thyroid cancer, insulinoma, kidney cancer, and skin cancer.
Regarding instant claim 26, conflicting claim 33 of the copending ‘730 application is drawn to embodiments in which the FAP-targeted conjugate is administered intravenously or intraperitoneally.
Regarding instant claim 27, conflicting claim 34 of the copending ‘730 application is drawn to embodiments in which the FAP-targeted conjugate is administered as part of a pharmaceutical composition comprising any one or more of a sterile diluent for injection, a saline solution, an oil, a polyol, glycerol, a solvent, an antibacterial or antifungal agent, an antioxidant, a chelating agent, a buffer, and an agent for adjustment of tonicity.
Regarding instant claim 28, conflicting claim 35 of the copending ‘730 application is drawn to embodiments in which the FAP-targeted conjugate is administered as part of a pharmaceutical composition comprising any of saline, phosphate buffered saline, glycerol, propylene glycol, liquid polyethylene glycol, a synthetic solvent, a paraben, chlorobutanol, phenol, ascorbic acid, thimerosal, gentisic acid, sodium bisulfite, EDTA, DTPA, DMSA, DMPS, acetates, citrates, phosphates, sodium chloride, mannitol, sorbitol, lecithin, and dextrose.
Regarding instant claim 29, conflicting claim 36 of the copending ‘730 application is drawn to a method of treating a cancer associated with the overexpression of FAP in a patient, the method comprising administering a FAP-targeted conjugate wherein the conjugate is labeled with a radionuclide. Additionally, Osterkamp teaches that FAP-targeting cyclic peptide radioconjugates can contain a variety of chelating groups, including NODAGA, DOTA, and NOTA (pg. 89-90). The substitution of the NODAGA in the last structure of conflicting claim 21 with NOTA would result in a compound that reads on the first structure of instant claim 21, rendering this method obvious.
Regarding instant claim 30, the last structure of conflicting claim 36 of the copending ‘730 application is the same as the structure of instant claim 22 other than the chelator moiety. Additionally, conflicting claim 30 of the copending application is drawn to a method of using this conjugate for imaging or diagnosing a cancer. Furthermore, Osterkamp teaches FAP-targeting radioconjugates may contain NOTA as the chelator (pg. 89-90). As described above, the combination of the reference application claims and the teachings of Osterkamp render the imaging use of the compound of instant claim 30 obvious.
Regarding instant claim 32, conflicting claim 37 of the copending ‘730 application is drawn to embodiments wherein the radionuclide is selected from the group consisting of In-111, Pb-203, Cu-64, Ga-68, and Zr-89.
Regarding instant claim 33, conflicting claim 38 of the copending ‘730 application is drawn to embodiments wherein the cancer comprises any selected from the group consisting of sarcoma, head and neck cancer, esophageal cancer, glioma, cholangiocarcinoma, breast cancer, lung cancer, prostate cancer, pancreatic cancer, thymus cancer, ovarian cancer, desmoid tumor, chordoma, colorectal cancer, anal cancer, neuroendocrine tumor, small intestine cancer, medullary thyroid cancer, cervical cancer, endometrial cancer, hepatocellular cancer, gastric cancer, adenoid cystic cancer, pheochromocytoma, differentiated thyroid cancer, insulinoma, kidney cancer, and skin cancer.
Regarding instant claim 34, conflicting claim 39 of the copending ‘730 application is drawn to embodiments in which the FAP-targeted conjugate is administered intravenously or intraperitoneally.
Regarding instant claim 35, conflicting claim 40 of the copending ‘730 application is drawn to embodiments in which the FAP-targeted conjugate is administered as part of a pharmaceutical composition comprising any one or more of a sterile diluent for injection, a saline solution, an oil, a polyol, glycerol, a solvent, an antibacterial or antifungal agent, an antioxidant, a chelating agent, a buffer, and an agent for adjustment of tonicity.
Regarding instant claim 36, conflicting claim 41 of the copending ‘730 application is drawn to embodiments in which the FAP-targeted conjugate is administered as part of a pharmaceutical composition comprising any of saline, phosphate buffered saline, glycerol, propylene glycol, liquid polyethylene glycol, a synthetic solvent, a paraben, chlorobutanol, phenol, ascorbic acid, thimerosal, gentisic acid, sodium bisulfite, EDTA, DTPA, DMSA, DMPS, acetates, citrates, phosphates, sodium chloride, mannitol, sorbitol, lecithin, and dextrose.
This is a provisional nonstatutory double patenting rejection.
Claims 21, 23-29, and 31-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30-41 of copending Application No. 18/537,730 in view of Lee (WO 2021/154921 A1).
The claims of copending Application No. 18/537,730 (henceforth referred to as the ‘730 application) are drawn to methods of using fibroblast activation protein (FAP)-targeted conjugate compounds labeled with radionuclides for imaging or treating cancer. These compounds are characterized by a structure comprising a cyclic peptide, a chelating moiety, and a linking group. The conjugates may be administered by multiple means and may be provided in various formulations.
The claims of the copending ‘730 application are not drawn to methods of using FAP targeting conjugate compounds possessing structures identical to those recited in instant claims 21 and 29)
Lee teaches radioconjugates of targeting cyclic peptides (Title and Abstract). More specifically, Lee teaches conjugates of the somatostatin receptor-targeting cyclic peptide TOC connected to a 1,4,7,10-tetraazacyclododecane-7acetamide-1,4,10-triacetic acid chelator through a PEG linker (pg. 2, line 34 through pg. 3, line 6). Lee teaches examples of such a conjugate in which the linker is composed of either 2 or 4 repeat PEG units (Figure 1C).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the methods of using FAP-targeted conjugates for the treatment of cancer of the copending ‘730 application by modifying the FAP-targeted conjugates through the substitution of the 10th, 11th, or 12th structure of conflicting claim 21 (upon which conflicting claims 30-41 depend) with the 2xPEG linker of Lee, as these linker groups perform the same function and serve the same purpose in these cyclic peptide radioconjugates (MPEP 2143 § 2143(I)(B)).
A person of ordinary skill in the art would have had a reasonable expectation of success in making this substitution because the 10th, 11th, and 12th structures of conflicting claim 21 of the ‘730 application depict cyclic peptides connected to a chelator with 1xPEG, 3xPEG, and 4xPEG containing linkers, respectively. These are very similar in chemistry and properties to the 2xPEG linker of Lee.
The skilled artisan would have been motivated to make this substitution because optimization of the distance between the cyclic peptide that contacts the target protein and the radionuclide is useful for the improvement of efficacy of a radioconjugate.
Regarding instant claims 21 and 23, conflicting claim 30 of the copending ‘730 application is drawn to a method of imaging or diagnosing a cancer associated with overexpression of FAP in a patient, the method comprising administering a FAP-targeted conjugate wherein the conjugate is labeled with a radionuclide, and imaging the patient. Additionally, Lee teaches targeting cyclic peptide radioconjugates may contain a linking group with 2xPEG (Figure 1C). The substitution of the 2xPEG linker in place of the 1x, 3x, or 4x PEG linkers of the 10th, 11th, or 12th structures of conflicting claim 21 would result in a structure identical to that of the second structure in instant claim 21 (which is the structure of instant claim 23), rendering these methods obvious.
Regarding instant claim 24, conflicting claim 31 of the copending ‘730 application is drawn to embodiments wherein the radionuclide is selected from the group consisting of In-111, Pb-203, Cu-64, Ga-68, and Zr-89.
Regarding instant claim 25, conflicting claim 32 of the copending ‘730 application is drawn to embodiments wherein the cancer comprises any selected from the group consisting of sarcoma, head and neck cancer, esophageal cancer, glioma, cholangiocarcinoma, breast cancer, lung cancer, prostate cancer, pancreatic cancer, thymus cancer, ovarian cancer, desmoid tumor, chordoma, colorectal cancer, anal cancer, neuroendocrine tumor, small intestine cancer, medullary thyroid cancer, cervical cancer, endometrial cancer, hepatocellular cancer, gastric cancer, adenoid cystic cancer, pheochromocytoma, differentiated thyroid cancer, insulinoma, kidney cancer, and skin cancer.
Regarding instant claim 26, conflicting claim 33 of the copending ‘730 application is drawn to embodiments in which the FAP-targeted conjugate is administered intravenously or intraperitoneally.
Regarding instant claim 27, conflicting claim 34 of the copending ‘730 application is drawn to embodiments in which the FAP-targeted conjugate is administered as part of a pharmaceutical composition comprising any one or more of a sterile diluent for injection, a saline solution, an oil, a polyol, glycerol, a solvent, an antibacterial or antifungal agent, an antioxidant, a chelating agent, a buffer, and an agent for adjustment of tonicity.
Regarding instant claim 28, conflicting claim 35 of the copending ‘730 application is drawn to embodiments in which the FAP-targeted conjugate is administered as part of a pharmaceutical composition comprising any of saline, phosphate buffered saline, glycerol, propylene glycol, liquid polyethylene glycol, a synthetic solvent, a paraben, chlorobutanol, phenol, ascorbic acid, thimerosal, gentisic acid, sodium bisulfite, EDTA, DTPA, DMSA, DMPS, acetates, citrates, phosphates, sodium chloride, mannitol, sorbitol, lecithin, and dextrose.
Regarding instant claim 29, conflicting claim 36 of the copending ‘730 application is drawn to a method of treating a cancer associated with the overexpression of FAP in a patient, the method comprising administering a FAP-targeted conjugate wherein the conjugate is labeled with a radionuclide. Additionally, Lee teaches targeting cyclic peptide radioconjugates may contain a linking group with 2xPEG (Figure 1C). The substitution of the 2xPEG linker in place of the 1x, 3x, or 4x PEG linkers of the 10th, 11th, or 12th structures of conflicting claim 21 would result in a structure identical to that of the second structure in instant claim 29 (which is the structure of instant claim 31), rendering these methods obvious.
Regarding instant claim 32, conflicting claim 37 of the copending ‘730 application is drawn to embodiments wherein the radionuclide is selected from the group consisting of In-111, Pb-203, Cu-64, Ga-68, and Zr-89.
Regarding instant claim 33, conflicting claim 38 of the copending ‘730 application is drawn to embodiments wherein the cancer comprises any selected from the group consisting of sarcoma, head and neck cancer, esophageal cancer, glioma, cholangiocarcinoma, breast cancer, lung cancer, prostate cancer, pancreatic cancer, thymus cancer, ovarian cancer, desmoid tumor, chordoma, colorectal cancer, anal cancer, neuroendocrine tumor, small intestine cancer, medullary thyroid cancer, cervical cancer, endometrial cancer, hepatocellular cancer, gastric cancer, adenoid cystic cancer, pheochromocytoma, differentiated thyroid cancer, insulinoma, kidney cancer, and skin cancer.
Regarding instant claim 34, conflicting claim 39 of the copending ‘730 application is drawn to embodiments in which the FAP-targeted conjugate is administered intravenously or intraperitoneally.
Regarding instant claim 35, conflicting claim 40 of the copending ‘730 application is drawn to embodiments in which the FAP-targeted conjugate is administered as part of a pharmaceutical composition comprising any one or more of a sterile diluent for injection, a saline solution, an oil, a polyol, glycerol, a solvent, an antibacterial or antifungal agent, an antioxidant, a chelating agent, a buffer, and an agent for adjustment of tonicity.
Regarding instant claim 36, conflicting claim 41 of the copending ‘730 application is drawn to embodiments in which the FAP-targeted conjugate is administered as part of a pharmaceutical composition comprising any of saline, phosphate buffered saline, glycerol, propylene glycol, liquid polyethylene glycol, a synthetic solvent, a paraben, chlorobutanol, phenol, ascorbic acid, thimerosal, gentisic acid, sodium bisulfite, EDTA, DTPA, DMSA, DMPS, acetates, citrates, phosphates, sodium chloride, mannitol, sorbitol, lecithin, and dextrose.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Eric P Mosher whose telephone number is (571)272-3258. The examiner can normally be reached Monday-Friday 9am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached at (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/E.P.M./Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
Prosecution Insights