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 .
Receipt is acknowledged of IDS filed on 06/12/2025 and 10/20/2025.
Claims 46-50 have been added.
Claims 16-21, 23-25, 27-31, 33-36, 38-44 and 46-50 are pending.
Claims 1-15, 22, 26, 32, 37, and 45 are cancelled.
Claims 27-31, 33-36 and 38-44 are withdrawn.
Note, this office action is to correct typographical errors from the non-final rejection office action dated 11/28/2025 and to acknowledge the traverse response for the election/restriction response dated 10/20/2025.
Election/Restrictions
Applicant's election with traverse of group I and species A-D in the reply filed on 10/20/2025 is acknowledged. The traversal is on the ground(s) that a search for a process of manufacturing and the search for relevant art and subsequent examination for the species would not be an undue burden on the Examiner. This is not found persuasive because searching all of the claims would require searching in numerous different classes and subclasses, as well as, a different searching focus depending on whether the product or processes are being searched. Furthermore claims to the different species recite the mutually exclusive characteristics of such species. Thus, the search would pose an undue burden on the Office.
The requirement is still deemed proper and is therefore made FINAL.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 16-21, 23-25 and 46-50 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. In the instant case, the specification shows a limited number of specific examples (species), that utilizes specific chelating agents, stabilizers, etc., in a specific process that allow for this radiochemical purity for at least 72 hours, as claimed. The few specific examples in the specification do not provide sufficient written description for the broad genus as claimed, that includes, a process using basically any chelating agent in any amount, any stabilizers and under very broad conditions. Applicant has failed to provide a representative number of species to support the broad genus claimed. This is unpredictable in the art as specific components and specific method are needed to reach this level of radiochemical purity for this specified time. Applicant’s specification states that “[radiopharmaceutical drug products] decay of the radionuclide occurs constantly, e.g. also during the manufacturing and during storage of the drug product, and the released high energy emissions induce the cleavage of the chemical bonds of the molecules which form part of the drug product” (Applicant’s specification, page 3, paragraph 4). Applicant’s specification further states that various strategies have been employed to attempt to correct this problem (Applicant’s specification, page 3, paragraph 6). Furthermore, LEMARPAX (The Lifecycle of Radiopharmaceuticals: From Research to Clinical Use) teaches, that most radiopharmaceuticals have a short radioactive half-life, sometimes even minutes, and must be manufactured sometimes even daily (page 6, paragraph 3-4). This further proves the unpredictability in the art of radiopharmaceutical purity over a prolonged time.
The dependent claims fall therewith.
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 16-21, 23-25 and 46-50 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 6, 7, 21 and 24 of U.S. Patent No. 10,596,276 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because:
The patent recites, a process for manufacturing a pharmaceutical aqueous solution (patent claim 1), the process according to claim 1, comprising:
(1) forming a complex of the radionuclide 177Lu and a somatostatin receptor binding peptide linked to the chelating agent DOTA by
(1.1) providing an aqueous solution comprising the radionuclide;
(1.2) providing an aqueous solution comprising a somatostatin receptor binding peptide linked to the chelating agent (which is a a cell receptor binding organic moiety linked to a chelating agent), and a first stabilizer against radiolytic degradation and optionally a second stabilizer against radiolytic degradation different from the first stabilizer; and
(1.3) mixing the solutions provided in steps (1.1) and (1.2) and heating the resulting mixture to form a solution comprising the complex;
(2) diluting the solution comprising the complex obtained by step (1) by
(2.1) providing an aqueous dilution solution optionally comprising at least one stabilizer against radiolytic degradation; and
(2.2.) mixing the solution comprising the complex obtained by step (1) with the dilution solution provided in step (2.1) to obtain the pharmaceutical aqueous solution;
This reads on instant claim 1, which recites a process for manufacturing a pharmaceutical aqueous solution, the process comprising diluting an aqueous complex solution with an aqueous dilution solution to form the pharmaceutical aqueous solution;
wherein the aqueous complex solution comprises:
a complex comprising (ai) the radionuclide 177Lull) and (aii) a cell receptor binding organic moiety linked to a chelating agent, and
at least one stabilizer(s) against radiolytic degradation; and
wherein the aqueous dilution solution comprises at least one stabilizer(s) against radiolytic degradation.
The patent further teaches the stabilizer/stabilizers provided in step (1.2) is/are present during the complex formation in step (1.3) in a total concentration of from 15 to 50 mg/mL (Patent claim 6) and the stabilizer/stabilizers provided in step (1.2) is/are present during the complex formation in step (1.3) in a total concentration of from 20 to 40 mg/mL (patent claim 7), which reads on instant claim 16 recitation of at least one stabilizer(s) against radiolytic degradation that is/are present in an amount to result in a concentration of at least 1 mg/mL in the pharmaceutical aqueous solution; and wherein the aqueous dilution solution comprises at least one stabilizer(s) against radiolytic degradation present in an amount to result in a concentration of at least 15 mg/mL in the pharmaceutical aqueous solution (instant claim 1). The patent recites the radionuclide 177Lu is present in a concentration that it provides a volumetric radioactivity of from 250 to 500 MBq/mL (patent claim 1), which reads on wherein the radionuclide is present in the pharmaceutical aqueous solution in a concentration that provides a volumetric radioactivity of at least 370 MBq/mL. The patent recites the pharmaceutical aqueous solution is substantially free of ethanol (patent claim 21), which reads on the pharmaceutical aqueous solution comprises less than 5% ethanol by weight. The patent recites the pharmaceutical aqueous solution the radiochemical purity (determined by HPLC) is maintained at ≥95% for at least 72 h when stored at 25° C (patent claim 24), which reads on the radiochemical purity of the pharmaceutical aqueous solution as determined by HPLC can be maintained at 95% for at least 72 hours when stored at 25C.
The difference between instant application and the patented claims is that the patent claims include additional limitations. Thus, the invention of the patent is in effect a “species” of the “generic” invention of the application claims. It has been held that the generic invention is “anticipated” by the “species”, and, therefore, the application claims are not patentably distinct from the claims of the patent and are rejected on the ground of nonstatutory obviousness-type double patenting. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Claims 16-21, 23-25, and 46-50 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 21 of copending Application No. 18/494,042 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The copending application recites in claim 1 a process for manufacturing a pharmaceutical aqueous solution, comprising:
providing a solution comprising a complex of the radionuclide 177Lu (Lutetium-177) and a somatostatin receptor binding peptide linked to the chelating agent DOTA; a first stabilizer against radiolytic degradation, and optionally a second stabilizer against radiolytic degradation different from the first stabilizer; which reads on wherein the aqueous complex solution comprises: (a) a complex comprising (ai) the radionuclide 177Luill) and (aii) a cell receptor binding organic moiety linked to a chelating agent, and (b) at least one stabilizer(s) against radiolytic degradation that is/are present in an amount to result in a concentration of at least 1 mg/mL in the pharmaceutical aqueous solution; and
diluting the solution comprising the complex with an aqueous dilution solution optionally comprising at least one stabilizer against radiolytic degradation to obtain the pharmaceutical aqueous solution; which reads on wherein the aqueous dilution solution comprises at least one stabilizer(s) against radiolytic degradation present in an amount to result in a concentration of at least 15 mg/mL in the pharmaceutical aqueous solution;
wherein if the solution comprising the complex comprises only the first stabilizer and not the second stabilizer, then the aqueous dilution solution comprises at least one stabilizer that is different from the first stabilizer, and in the obtained pharmaceutical aqueous solution, the radionuclide 177Lu is present in a concentration that it provides a volumetric radioactivity of from 250 to 500 MBq/mL and the stabilizers are present in a total concentration of from 0.2 to 20.0 mg/mL, which reads on at least one stabilizer(s) against radiolytic degradation that is/are present in an amount to result in a concentration of at least 1 mg/mL in the pharmaceutical aqueous solution; and the at least one stabilizer(s) against radiolytic degradation present in an amount to result in a concentration of at least 15 mg/mL in the pharmaceutical aqueous solution; wherein the radionuclide is present in the pharmaceutical aqueous solution in a concentration that provides a volumetric radioactivity of at least 370 MBq/mL.
The pharmaceutical aqueous solution according to claim 20, which is free of ethanol (copending application claim 21).
The copending application does not teach the radiochemical purity of the pharmaceutical aqueous solution as determined by HPLC can be maintained at 95% for at least 72 hours when stored at 25 0C.
With regard to claim 1, the wherein limitations of these claims, are considered to simply express the intended result of a process step positively recited, which is not given patentable weight (See MPEP 2111.04: [T]he court noted (quoting Minton v. Nat'lAss'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQgd 1614, 1690 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.'" Hoffer v. Microsoft Corp., 405 F.3d 1396, 1399, 74 USPQgd 1481, 1483 (Fed. Cir. 2005).). In the instant case, the copending application teaches all active steps and components and would therefor have the same ability of having a “radiochemical purity of the pharmaceutical aqueous solution as determined by HPLC can be maintained at 95% for at least 72 hours when stored at 25C” unless proven otherwise.
This is a provisional nonstatutory double patenting rejection.
Claims 16-21, 23-25, and 46-50 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 20, 22 and 31-32 of copending Application No. 18/791,288 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The copending application recites a 177Lu-Prostate-Specific-Membrane Antigen Imaging and Therapy complex (claim 1), which reads on a complex comprising 177Lu and a cell receptor binding organic moiety linked to a chelating agent. The composition further comprises 28 mg/ml of ascorbic acid (claim 22), which reads on stabilizer and is a solution (claim 22).
The composition does not comprise ethanol.
The composition has a radiochemical purity of 98.0% or greater at 72 hours after production (claim 20).
The reference does not specifically teach the volumetric radioactivity as claimed by the Applicant. The volumetric radioactivity is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of the ordinary skill to determine the optimal volumetric radioactivity in order to best achieve desired results, such as having enough radioactivity for administration so the composition performs as desired when split into doses, especially since the claims state that a certain radioactivity level is needed per dose (claims 31-32). Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of the volumetric radioactivity would have been obvious at the time of Applicant’s invention.
This is a provisional nonstatutory double patenting rejection.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over CHEN (2011/0206.606 A1).
Regarding claim 16, CHEN teaches a method of making a pharmaceutical aqueous solution (Example 22) comprising:
diluting an aqueous complex solution with an aqueous dilution solution to form the pharmaceutical aqueous solution;
wherein the aqueous complex solution comprises the following in an aqueous form (page 29, paragraph 0314):
(a) a complex comprising
(ai) the radionuclide 177Lu (page 29, paragraph 0314) and
(aii) Compound B, which comprises DOTA linked to a Gastrin Releasing Peptide receptor targeting agent (page 1, paragraph 0013), which is a cell receptor binding organic moiety linked to a chelating agent, and
(b) L-Selenomethionine (page 29, paragraph 0314), which is a stabilizer against radiolytic degradation, and is present in a concentration of 2.94 mg/mL (page 29, paragraph 0314) in the pharmaceutical aqueous solution;
wherein the aqueous dilution solution comprises
Sodium ascorbate in an aqueous solution (page 29, paragraph 0314) which is a stabilizer against radiolytic degradation, in a concentration of at least 50 mg/mL (page 29, paragraph 0314) in the pharmaceutical aqueous solution;
wherein the 177Lu is present in the pharmaceutical aqueous solution in a concentration of roughly 817 MBq/mL (110.5 mCi=4088.5 MB, which is in a total solution of roughly 5mL);
the pharmaceutical aqueous solution does not comprise ethanol (page 29, paragraph 0314)
and the radiochemical purity of the pharmaceutical aqueous solution as determined by HPLC can be maintained at 99.8% for at least 120 hours (table 23) when stored at room temperature (page 29, paragraph 0315), which is roughly 25C.
Regarding claim 17, CHEN teaches adding an ascorbic acid solution or a gentisic acid solution to the aqueous complex solution (example 9 and page 24, paragraph 0266).
Regarding claim 18, CHEN teaches adding an ascorbic acid solution to the already complexed solution (example 8 and page 23, paragraph 0266), which reads on wherein the at least one stabilizer against radiolytic degradation in the aqueous dilution solution comprises ascorbic acid.
Regarding claim 19-21, the pharmaceutical aqueous solution does not comprise ethanol (page 29, paragraph 0314)
Regarding claim 23 and 50, the radiochemical purity of the pharmaceutical aqueous solution as determined by HPLC can be maintained at 99.8% for at least 120 hours (table 23) when stored at room temperature (page 29, paragraph 0315), which is roughly 25C.
Regarding claim 24, 48 and 49, the radiopharmaceutical has DOTA as the chelator (Page 19, paragraph 0225 and claim 16).
Regarding claim 25, the radiopharmaceutical has a Gastrin Releasing Peptide receptor (GRP-Receptor) targeting molecule attached to the chelator (abstract and claims 13, 16, 22), that is in the form of an antagonist (Page 9, paragraph 0120), which reads on a GRP receptor peptide antagonist binding moiety.
Regarding claim 46 and 47, a NaOAc buffer is added to the solution for a pH of 4.8 (page 29, paragraph 0314).
CHEN further teaches that injections of the composition uses a quantity of radioactivity that is sufficient to permit imaging or in the case of radiotherapy, to cause damage or ablation of the targeted tissue, but not so much that substantive damage is caused to non-target (normal tissue) (Page 12, paragraph 0145).
Although reference does not specifically teach the volumetric radioactivity as claimed by the Applicant. The volumetric radioactivity is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of the ordinary skill to determine the optimal volumetric radioactivity in order to best achieve desired results, such as having an appropriate amount of radioactivity to produce images and cause damage to targeted cancer tissue, but not so much to damage non targeted healthy tissue. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of the volumetric radioactivity would have been obvious at the time of Applicant’s invention.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMANTHA L. MEJIAS whose telephone number is (703)756-5666. The examiner can normally be reached M-F.
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, MICHAEL HARTLEY can be reached at (571) 272-0616. 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.
/S.L.M./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618