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 and species of NODAGA-GSAO ((1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid)-(4-(N-(S-glutathionylacetyl)amino)phenylarsenous acid)) that is a compound of formula (Y) with A = -As(OH)2, R1 = R2 = R3 = R4 = H; R5 = -NHCH2COOH, L = NODAGA and 177Lu as the radioisotope in the reply filed on September 2, 2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Drawings
The drawings are objected to because in Figure 27, the number and smallness of the symbols means that all of the various lines cannot be readily identified in this figure. In figures 28 – 33, the numbers on the axes of the graphs cannot be read. In Figure 43, the presence of error bars completely covers the symbol used for the small intestine data. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities: various chemical formulas throughout the specification are blurry (e.g., on pages 3 and 22) such that the chemical structures cannot be clearly identified.
Appropriate correction is required.
Claim Objections
Claim 3 is objected to because of the following informalities: the complete chemical names for each of the abbreviations found in this claim are not presented the first time the abbreviation is used in the claims. Appropriate correction is required.
Claims 20 and 23 are objected to because of the following informalities: a space should be added between the numerical value and the abbreviation M for molarity. Appropriate correction is required.
Claim Rejections - 35 USC § 112 – Written Description
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 1 – 4, 16 – 18, 20 – 25, 27, 41 and 43 are 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. This is a written description rejection.
A generic claim may define the boundaries of a vast genus of chemical compounds, and yet the question may still remain whether the specification, including original claim language, demonstrates that the applicant has invented species sufficient to support a claim to a genus. The problem is especially acute with genus claims that use functional language to define boundaries of a claimed genus. In such a case, the functional claim may simply claim a desired result, and may do so without describing species that achieve that result. But the specification must demonstrate that the applicant has made a generic invention the achieves the claimed results and do so by showing that that the applicant has invented species sufficient to support a claim to a functionally-defined genus.
Two different aspects of the claims fail to fully satisfy the written description requirement – low molecular weight thiols and the esters, prodrugs and derivatives for compounds of formula (Y) as defined in claim 2 and formula (II) in claim 4.
A discussion of the meaning of low molecular weight thiols is present in the specification as filed (¶ [0185] of the PGPub of the instant application) but contains no reference to the molecular weight of the molecules. The definition focuses on the function of the compounds and no mention of size although given the description, there would seem to be some limitation implied by the phrase “low molecular weight”. Reference is made to two different NPL documents but essential subject matter cannot be incorporated by reference to such documents. Some examples of specific thiols within this genus are given in both the specification and claims but claims such as claim 1 are not limited to those compounds. This claim language would also encompass thiols discovered in the future that have this function that were either not known or known compounds that were not known to be involved in the functions recited in the definition. Between the breadth in the definition and the lack of any reference to molecular weight in the definition, the specific compounds do not form a representative number of species within the large possible genus of low molecular weight thiol compounds encompassed by the claims.
The written description requirement is also not fully satisfied for compounds of formula (Y) as defined in claim 2 and formula (II) in claim 4 because of lack of a sufficient number of species within the scope of each genus being disclosed in the disclosure as originally filed. Any ester, prodrug or derivative are encompassed by the claims but the Examiner was unable to locate any examples of such compounds in the disclosure as filed. The claims are also directed to a process of preparing and not a method of using that could provide some information as to the activity that would need to be maintained when considering how to prepare a suitable prodrug. The claimed formula can be altered in any manner and still considered a derivative of the shown formula. Given the breadth of compounds encompassed by each of these claim limitations and the lack of disclosure of sufficient species within the claimed genus, the written description requirement for esters, prodrugs and derivatives has not been fully satisfied.
The dependent claims fall therewith.
Claim Rejections - 35 USC § 112 – Indefiniteness
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.
Claims 1 – 4, 16, 20 - 25, 27, 41 and 43 are 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.
The definition at ¶ [0185] given for “low molecular weight thiols” does not provide a sufficiently clear definition of this phrase to determine the scope of the thiol compounds encompassed by the claimed. On its face, “low molecular weight” is a relative term and where the threshold for a low molecular compound is and can vary from one artisan to another. Here, however, Applicants set forth a definition of this phrase that contains no reference to molecular weight of the compounds. There are cysteine containing proteins present in cells that can have function related to cellular redox homeostasis and protection from reactive chemical and electrophilic species. Despite their large molecular weight, would such compounds fall within the scope of low molecular weight thiols in view of the definition in the specification that is silent as to molecular weight? That cannot be determined sufficiently to render the claim scope definite.
The dependent claims fall therewith.
Please clarify.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1 – 4, 16 – 18, 20 – 25, 27, 41 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Ho Shon et al. (Methods in Molecular Biology, 2019; cited on IDS filed April 30, 2024) in view of Chen et al. (US 2007/0269375; cited on IDS filed August 6, 2025).
Ho Shon et al. discloses the labeling of NODAGA-GSAO with the radioisotope 68Ga (e.g., Figure 1). In section 3.4, the procedure used is detailed and the trivalent arsenical compound NODAGA-GSAO was mixed with the antioxidant ascorbic acid (100 µL of a 0.25 M solution in a final volume of 3.85 mL for a final concentration of about 0.0065 M) in water and the 68Ga containing eluate from the SCX column and after a brief mixing, allowed to react at room temperature for 10 minutes. 3 mL of phosphate buffer was then added to the reaction vial, reading on treating the adduct with anions as required by instant claim 25 (see also original claim 26 of the instant application).
Adding the radioisotope in the presence of a low molecular weight thiol such as glutathione is not disclosed and the use of other isotopes such as 177Lu is not disclosed.
Chen et al. discloses methods of making stabilized radiopharmaceutical formulations and stabilizers that improve the radiostability of the radiotherapeutic and radiodiagnostic compositions (whole document, e.g., abstract). For radiotherapeutic and radiodiagnostic compounds, radiolytic damage to the radiolabeled compound itself can be a serious problem during the preparation, purification, storage and/or shipping of a radiolabeled radiotherapeutic or radiodiagnostic compound, prior to its intended use (¶ [0015]). Compounds such as ascorbic acid or water soluble sulfur containing compounds can be used as stabilizers (¶¶ [0026] and [0034]). With the thiol compounds, it is highly efficacious to use them in combination with sodium ascorbate or other pharmaceutically acceptable forms of ascorbic acid and its derivatives and is most preferably added after complexation is complete (¶ [0034]). A variety of isotopes can be used for complexation including 64Cu, 68Ga and 177Lu with isotope choice determined based on the desired therapeutic or diagnostic application (¶ [0058]). One or more radiostabilizers are required of the stabilized formulations (¶ [0163]). The concentration of ascorbic acid exemplified in a preferred embodiment is 10 – 100 mg/mL ascorbic acid (176.1 g/ml, 0.057 – 0.57 M) (¶ [0166]). Glutathione was amongst the thiol compounds tested as stabilizers (Table 1, p 16 and ¶ [0210]). In example 14, a composition of 3.33 mg/mL glutathione (307.32 g/mol, 0.01 M) was investigated. For complexing 177Lu with the chelator, a reaction mixture of sodium acetate buffer, 177LuCl3 and the chelator containing compound were mixed, heated to 100°C for 5 minutes and then cooled for 5 minutes in an ambient temperature water bath (¶ [0286).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to include ascorbic acid and a thiol such as glutathione in the procedure disclosed by Ho Shon et al. for complexation a radioisotope to NODAGA-GSAO. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Chen et al. discloses that radiostabilizers, alone or in combination, can add to stabilize formulations comprising radioisotopes to reduce radiolytic damage to the radiolabeled compound. GSAO contains a thioether bond that would be known to one of ordinary skill in the art to be susceptible to oxidation and materials such as ascorbic acid and thiol containing compounds such as glutathione that are known radiostabilizers can be present to stabilize radiolabeled molecules. One such stabilizer, ascorbic acid, is used in the method disclosed by Ho Shon et al. and Chen et al. provides additional information as to suitable concentrations of ascorbic acid. Chen et al. discloses that combinations of stabilizers can be used and while addition after complexation is preferred, this does not rise to the level of teaching away from the presence of the radiostabilizers during complexation. Ho Shon et al. complexes 68Ga at room temperature while Chen et al. complexes 177Lu at the elevated temperature of 100°C. Depending on the radioisotope used, the particular chelator and other parts of the molecule being labeled with the radioisotope and the nature and number of radiostabilizers used, the concentration of each ingredient and process parameters such as the time and temperature for the complexation reaction are results effects variables that would be routinely optimized by one of ordinary skill in the art. There is no evidence of record as to the criticality of these parameters such as the particular radiostabilizer and/or their concentration.
The addition of the anions phosphate as required by claim 25 is taught by Ho Shon et al. although the effects of such addition of dissociation of the radiolabeled trivalent arsenical compound and the low molecular weight thiol is not explicitly disclosed. The patentability of the process lies in the steps taken and not the explicit appreciation of what occurs during such a step and/or the reason for the addition of the same ingredient at the same point in the method. As the prior art adds phosphate anions to the radiolabeled adduct as is required by the claims, this step is rendered obvious by the applied prior art.
As to claim 27, an explicit purification step is not disclosed although issues with radiolytic damage during purification is set forth by Chen et al. It would have been obvious to one of ordinary skill in the art, in view of this teaching and their knowledge, to purify the complexation reaction product to increase the purity of the material and also remove materials such as uncomplexed radioisotopes.
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 1 – 4, 16 – 18, 20 – 25, 27, 41 and 43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 19 of U.S. Patent No. 12,296,030 in view of Ho Shon et al. (Methods in Molecular Biology, 2019; cited on IDS filed April 30, 2024) in view of Chen et al. (US 2007/0269375; cited on IDS filed August 6, 2025). The claims of US’030 recite compounds falling within the scope of the claims that are complexed with various isotopes as set forth in claim 1. The compounds can be used in diagnostic or treatment methods (claims 5 – 12). Claim 13 recites a method of making the claimed compounds using eluted 68Ga in a buffer.
That the complexation reaction is carried out in the presence of a thiol such as glutathione or an antioxidant such as ascorbic acid is not claimed. 177Lu as the isotope is also not claimed.
Ho Shon et al. and Chen et al. are discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to include ascorbic acid and a thiol such as glutathione when preparing the compounds claimed in US’030. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Ho Shon et al. discloses a procedure for radiolabeling this compound that includes ascorbic acid. Chen et al. discloses that radiostabilizers, alone or in combination, can add to stabilize formulations comprising radioisotopes to reduce radiolytic damage to the radiolabeled compound. GSAO contains a thioether bond that would be known to one of ordinary skill in the art to be susceptible to oxidation and materials such as ascorbic acid and thiol containing compounds such as glutathione that are known radiostabilizers can be present to stabilize radiolabeled molecules. One such stabilizer, ascorbic acid, is used in the method disclosed by Ho Shon et al. and Chen et al. provides additional information as to suitable concentrations of ascorbic acid. Chen et al. discloses that combinations of stabilizers can be used and while addition after complexation is preferred, this does not rise to the level of teaching away from the presence of the radiostabilizers during complexation. Ho Shon et al. complexes 68Ga at room temperature while Chen et al. complexes 177Lu at the elevated temperature of 100°C. Depending on the radioisotope used, the particular chelator and other parts of the molecule being labeled with the radioisotope and the nature and number of radiostabilizers used, the concentration of each ingredient and process parameters such as the time and temperature for the complexation reaction are results effects variables that would be routinely optimized by one of ordinary skill in the art. There is no evidence of record as to the criticality of these parameters such as the particular radiostabilizer and/or their concentration.
The addition of the anions phosphate as required by claim 25 is taught by Ho Shon et al. although the effects of such addition of dissociation of the radiolabeled trivalent arsenical compound and the low molecular weight thiol is not explicitly disclosed. The patentability of the process lies in the steps taken and not the explicit appreciation of what occurs during such a step and/or the reason for the addition of the same ingredient at the same point in the method. As the prior art adds phosphate anions to the radiolabeled adduct as is required by the claims, this step is rendered obvious by the applied prior art.
As to claim 27, an explicit purification step is not disclosed although issues with radiolytic damage during purification is set forth by Chen et al. It would have been obvious to one of ordinary skill in the art, in view of this teaching and their knowledge, to purify the complexation reaction product to increase the purity of the material and also remove materials such as uncomplexed radioisotopes.
Claims 1 – 4, 16 – 18, 20 – 25, 27, 41 and 43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 6, 14 – 29 and 57 - 59 of copending Application No. 18/299,304 in view of Ho Shon et al. (Methods in Molecular Biology, 2019; cited on IDS filed April 30, 2024) in view of Chen et al. (US 2007/0269375; cited on IDS filed August 6, 2025). The claims of US’304 recite compounds falling within the scope of the instant claims (e.g., claims 1 and 57 – 59) with claimed isotopes including 177Lu (claim 1 and 58). Methods of treating a neoplastic condition by administering such compounds (claims 15 – 29) are also present.
That the complexation reaction is carried out in the presence of a thiol such as glutathione or an antioxidant such as ascorbic acid is not claimed.
Ho Shon et al. and Chen et al. are discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to include ascorbic acid and a thiol such as glutathione when preparing the compounds claimed in US’304. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Ho Shon et al. discloses a procedure for radiolabeling this compound that includes ascorbic acid. Chen et al. discloses that radiostabilizers, alone or in combination, can add to stabilize formulations comprising radioisotopes to reduce radiolytic damage to the radiolabeled compound. GSAO contains a thioether bond that would be known to one of ordinary skill in the art to be susceptible to oxidation and materials such as ascorbic acid and thiol containing compounds such as glutathione that are known radiostabilizers can be present to stabilize radiolabeled molecules. One such stabilizer, ascorbic acid, is used in the method disclosed by Ho Shon et al. and Chen et al. provides additional information as to suitable concentrations of ascorbic acid. Chen et al. discloses that combinations of stabilizers can be used and while addition after complexation is preferred, this does not rise to the level of teaching away from the presence of the radiostabilizers during complexation. Ho Shon et al. complexes 68Ga at room temperature while Chen et al. complexes 177Lu at the elevated temperature of 100°C. Depending on the radioisotope used, the particular chelator and other parts of the molecule being labeled with the radioisotope and the nature and number of radiostabilizers used, the concentration of each ingredient and process parameters such as the time and temperature for the complexation reaction are results effects variables that would be routinely optimized by one of ordinary skill in the art. There is no evidence of record as to the criticality of these parameters such as the particular radiostabilizer and/or their concentration.
The addition of the anions phosphate as required by claim 25 is taught by Ho Shon et al. although the effects of such addition of dissociation of the radiolabeled trivalent arsenical compound and the low molecular weight thiol is not explicitly disclosed. The patentability of the process lies in the steps taken and not the explicit appreciation of what occurs during such a step and/or the reason for the addition of the same ingredient at the same point in the method. As the prior art adds phosphate anions to the radiolabeled adduct as is required by the claims, this step is rendered obvious by the applied prior art.
As to claim 27, an explicit purification step is not disclosed although issues with radiolytic damage during purification is set forth by Chen et al. It would have been obvious to one of ordinary skill in the art, in view of this teaching and their knowledge, to purify the complexation reaction product to increase the purity of the material and also remove materials such as uncomplexed radioisotopes.
This is a provisional nonstatutory double patenting rejection.
Claims 1 – 4, 16 – 18, 20 – 25, 27, 41 and 43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 37 - 50 of copending Application No. 19/172,178 in view of Ho Shon et al. (Methods in Molecular Biology, 2019; cited on IDS filed April 30, 2024) in view of Chen et al. (US 2007/0269375; cited on IDS filed August 6, 2025). The claims of US’178 recite compounds falling within the scope of the instant claims that can be radiolabeled with 68Ga (e.g., claim 38). The complexation process can occur in the presence of ascorbic acid (claims 41 and 42). Method of using this compound for visualizing cell death (claims 44 – 47) and assessing a response of a subject to a therapy intended to cause a change in the level of cell death (claims 48 – 50) by administering the claimed compound are also present.
That the complexation reaction is carried out in the presence of both a thiol such as glutathione or an antioxidant such as ascorbic acid is not claimed. 177Lu as the isotope is also not claimed.
Ho Shon et al. and Chen et al. are discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to include ascorbic acid and a thiol such as glutathione when preparing the compounds claimed in US’178. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Ho Shon et al. discloses a procedure for radiolabeling this compound that includes ascorbic acid. Chen et al. discloses that radiostabilizers, alone or in combination, can add to stabilize formulations comprising radioisotopes to reduce radiolytic damage to the radiolabeled compound. GSAO contains a thioether bond that would be known to one of ordinary skill in the art to be susceptible to oxidation and materials such as ascorbic acid and thiol containing compounds such as glutathione that are known radiostabilizers can be present to stabilize radiolabeled molecules. One such stabilizer, ascorbic acid, is used in the method disclosed by Ho Shon et al. and Chen et al. provides additional information as to suitable concentrations of ascorbic acid. Chen et al. discloses that combinations of stabilizers can be used and while addition after complexation is preferred, this does not rise to the level of teaching away from the presence of the radiostabilizers during complexation. Ho Shon et al. complexes 68Ga at room temperature while Chen et al. complexes 177Lu at the elevated temperature of 100°C. Depending on the radioisotope used, the particular chelator and other parts of the molecule being labeled with the radioisotope and the nature and number of radiostabilizers used, the concentration of each ingredient and process parameters such as the time and temperature for the complexation reaction are results effects variables that would be routinely optimized by one of ordinary skill in the art. There is no evidence of record as to the criticality of these parameters such as the particular radiostabilizer and/or their concentration.
The addition of the anions phosphate as required by claim 25 is taught by Ho Shon et al. although the effects of such addition of dissociation of the radiolabeled trivalent arsenical compound and the low molecular weight thiol is not explicitly disclosed. The patentability of the process lies in the steps taken and not the explicit appreciation of what occurs during such a step and/or the reason for the addition of the same ingredient at the same point in the method. As the prior art adds phosphate anions to the radiolabeled adduct as is required by the claims, this step is rendered obvious by the applied prior art.
As to claim 27, an explicit purification step is not disclosed although issues with radiolytic damage during purification is set forth by Chen et al. It would have been obvious to one of ordinary skill in the art, in view of this teaching and their knowledge, to purify the complexation reaction product to increase the purity of the material and also remove materials such as uncomplexed radioisotopes.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618
