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 .
Claims 1, 2, 21, and 22 have been amended.
Claims 1-3, 6-7, 10-17 and 21-22 are pending.
Claims 4, 5, 8, 9, and 18-20 are cancelled.
Claim 17 is withdrawn.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 103
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 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.
Claims 1-3, 6-7, 10-17 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over ASTI (Development of a simple kit-based method for preparation of pharmaceutical-grade 68Ga-DOTATOC. Nuclear Medicine Communications. 2014.) in view of WOUTERS (US 11,027,031 B2).
Regarding claim 1, ASTI teaches a kit based method for preparation of 68Ga-DOTATOC (abstract) that comprises: DOTATOC (page 503, paragraph 2), which is a chelating agent, DOTA, linked to a somatostatin receptor, also known as edotreotide; ascorbic acid (page 503, paragraph 6), which reads on stabilizer; sodium acetate (page 503, paragraph 6), which reads on a buffer. The composition does not list any sequestering agent or metal inhibitor. The kit is designed to be lyophilized (abstract). The composition is a single vial kit (Figure 1)
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Regarding claim 2, ASTI teaches the composition comprises DOTATOC (page 503, paragraph 2), also known as edotreotide; ascorbic acid (page 503, paragraph 6), which reads on stabilizer; sodium acetate (page 503, paragraph 6), which reads on a buffer. The composition does not list any co-chelating agents capable of inactivating contaminating metals other than the desired radioisotope. The pH of the solution was 3.3 (page 503, paragraph 6). The composition is radiolabeled with gallium-68 (page 503, paragraph 6). The radiochemical purity is 99% (page 507, paragraph 3).
Regarding claim 3, ASTI teaches the chelating agent is DOTA (page 503, paragraph 2).
Regarding claim 6, ASTI teaches sodium acetate is used as a buffer (page 503, paragraph 6).
Regarding claim 7, ASTI teaches the pH of the solution was 3.3 (page 503, paragraph 6).
Regarding claim 10 and 11, ASTI teaches the composition is radiolabeled with gallium-68 (page 503, paragraph 6).
Regarding claims 12-16, ASTI teaches the radiochemical purity is 99% (page 507, paragraph 3), radiochemical purity is the percentage of total radioactivity in a radiopharmaceutical that is in the desired chemical form, this would mean at most only 1% of gallium-68 in colloidal form and gallium-68 (III) iron would be present.
Regarding claim 21, ASTI teaches a kit based method for preparation of 68Ga-DOTATOC (abstract) that comprises: DOTATOC (page 503, paragraph 2), which is a chelating agent, DOTA, linked to a somatostatin receptor; ascorbic acid (page 503, paragraph 6), which reads on stabilizer; sodium acetate (page 503, paragraph 6), which reads on a buffer. The composition does not list any co-chelating agents capable of inactivating contaminating metals other than the desired radioisotope. The composition is further radiolabeled with gallium-68 (page 503, paragraph 6). The composition is a single vial kit (Figure 1).
Regarding claim 22, ASTI teaches the composition comprises DOTATOC (page 503, paragraph 2), also known as edotreotide; ascorbic acid (page 503, paragraph 6), which reads on stabilizer; sodium acetate (page 503, paragraph 6), which reads on a buffer. The composition does not list any sequestering agents or metal inhibitors. The pH of the solution was 3.3 (page 503, paragraph 6). The composition is radiolabeled with gallium-68 (page 503, paragraph 6). The radiochemical purity is 99% (page 507, paragraph 3). The composition is a single vial kit (Figure 1).
ASTI does not teach adding mannitol or explicitly lyophilizing the kit.
WOUTERS teaches a vial kit composition that comprises DOTA, a buffer and gallium-68 with a pH of 3-5 (claim 1). The components are lyophilized (claim 1). The composition further comprises mannitol, which is used as a cryoprotectant to stabilize the composition during lyophilization (column 12, paragraph 7). WOUTERS teaches lyophilizing the kit ensures a longer shelf life (column 8, paragraph 7).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate mannitol. The person of ordinary skill in the art would have been motivated to make those modifications, because it acts as a cryoprotectant to stabilize the composition during lyophilization and reasonably would have expected success because the references are in the same field of endeavor such as vial kits of lyophilized components that include DOTA, a buffer and gallium-68.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate lyophilizing the kit. The person of ordinary skill in the art would have been motivated to make those modifications, because it ensures a longer shelf life, and reasonably would have expected success because the references are in the field of endeavor such as vial kits of lyophilized components that include DOTA, a buffer and gallium-68 and ASTI teaches the kit is meant to be lyophilized.
The reference does not specifically teach the amounts of components, such as DOTATOC, ascorbic acid, sodium acetate, mannitol or gallium-68, as claimed by the Applicant. The amounts of components are 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 amounts of the listed components in order to best achieve desired results, such as chelating enough gallium-68, having a stable compound, that is buffered to the correct pH, protected from lyophilization via a cryoprotectant, and enough radioisotope for clear labeling. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of amounts of the listed components would have been obvious at the time of Applicant’s invention.
Response to Arguments
Applicant argues, ASTI does not form a lyophilized kit and at most states that a "lyophilized kit was proposed." Abstract, page 509. Therefore ASTI fails to disclose a lyophilized kit. Proposing a lyophilized kit is far different from actually making a stable lyophilized kit. Applicant submits that development of a lyophilized composition is a complex procedure and the choice of excipients and their respective amounts are extremely critical in developing a stable, lyophilized composition with desirable properties such as a suitable and stable cake structure, ease of reconstitution, moisture content and long term storage stability. Based on Applicant's experience, the components of the formulation such as the buffer and the bulking agents may crystallize and separate during storage, volatile buffers such as formate may be lost during lyophilization. Therefore, it is very difficult for a person of skill in the art to predict that ASTl's suggested combination of sodium formate and ascorbic acid can be actually successfully translated into a lyophilized product with acceptable stability without performing additional experiments -necessary to move from ASTI's proposed lyophilized product into an actual lyophilized product. In summary, because of the unpredictability of forming a lyophilized composition from the disclosure of ASTI, there is no reasonable expectation of success.
The examiner does not find the argument persuasive because the prior art teaches the same components of the lyophilized kit recited in instant claim 1 and therefor has the potential to lyophilized successfully. Furthermore, it would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate lyophilizing the kit. The person of ordinary skill in the art would have been motivated to make those modifications, because it ensures a longer shelf life, and reasonably would have expected success because the references are in the field of endeavor such as vial kits of lyophilized components that include DOTA, a buffer and gallium-68 and ASTI teaches the kit is meant to be lyophilized.
Applicant argues, ASTI also fails to disclose a single vial, lyophilized kit. At page 504, right column, ASTI describes the process of adding the radiolabeled elution to the vial: the vial was prefilled with DOTATOC solution, ascorbic acid and sodium formate solution and then the elution product added. After the elution is added "[t]he mixture was. . . manually diluted with 6 ml of the 1 mol/1 sodium ascorbate solution contained in the formulation syringe." Page 504, right column.
The examiner does not find the argument persuasive because as discussed above, all reactants are consolidated into one vial
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(figure 1), which would read on a single vial.
Applicant argues, Further, combining ASTI with Wouters would result in a lyophilized composition that includes a metal inhibitor because Wouters teaches the necessity of including a metal inhibitor/sequestering agent and also teaches away from excluding a metal inhibitor/sequestering
agent. Example 2 of Wouters discloses the radiolabeling yield for different compositions made
with and without a metal inhibitor. The radiolabeling yields are significantly higher with a metal
inhibitor than without a metal inhibitor. One of skill in the art relying on Wouters would have
been taught away from excluding a metal inhibitor because of the undesirable reduction in
radiolabeling yield such an exclusion would cause.
The examiner does not find the argument persuasive because, WOUTERS is not cited for its use of metal inhibitor/sequestering agent, but rather for its use of mannitol. ASTI does not teach using a metal inhibitor or sequestering agent.
Conclusion
No claims are allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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.
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/S.L.M./ Examiner, Art Unit 1618 /JAKE M VU/Primary Examiner, Art Unit 1618
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