DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claims Status
Claims 15-19 are pending in the application.
Any objections and/or rejections from previous office actions that have not been reiterated in this office action are obviated.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claim(s) 15,16,18 and 19 is/are rejected under pre-AIA 35 U.S.C. 102b as being anticipated by Edwards et al. (Proc. SPIE 2006 Vol. 6097, 609703-1 to 609703-8) as stated in the office action mailed 4/21/25.
Applicant asserts that Edwards utilizes heat to drive equilibrium towards the products side of the reaction, and then allows the completed reaction to sit for up to 24 hours. It is important to note that the 24 hour room temperature step in Edwards was done solely for the purpose of post-reaction stability testing, not for conducting the reaction itself. In fact, Edwards discloses that "for complete incorporation [i.e., a successful chelation reaction] of 64Cu as well as radionuclides such as 177Lu and 68Ga, into the tetraazamacrocyclic chelator DOTA, the radiolabeling mixtures must be heated to relatively high temperatures for one hour >80°C”. Edwards also teaches that additional energy was needed to overcome the high activation energy barrier that macrocyclic compounds, like DOTA-TATE, are known for. To arrive at the claimed invention, Edwards would have to be modified by removing the essential heating step. Meanwhile, the reaction of the present disclosure, as set forth in amended claim 15, merely rests at room temperature for 10 minutes. Indeed, the present invention provides for a reaction that takes place in approximately 1/6th the time and 1/4th the temperature, but produces radiochemical yields and purities above 90%.
The instant claims use the open language “comprising” and does not exclude other method steps, such as heating the reaction mixture.
The reference of Edwards does not state that the radiolabeling reaction does not continue during the 24 hour room temperature step and therefore, further radiolabeling may occur during this 24 hour time period at room temperature.
Also, the instant claims do not recite radiochemical yields, purities and/or a total reaction time. The instant claim 15 recites “reaction solution at ambient temperature for at least 10 minutes” which does not provide un upper limit to the time frame for the reaction and/or exclude any prior or subsequent method steps of heating and therefore, the claims are not commensurate in scope.
Applicant asserts that a prior art reference must be considered in its entirety, including portions that would lead away from the claimed invention. MPEP 2141.02. Here, the references create a strong technical bias that a high-temperature heating step is an essential and non-negotiable prerequisite for a successful reaction. As noted above, Edwards explicitly states that for a successful reaction (i.e., complete incorporation), "the radiolabeling mixtures must be heated to relatively high temperatures for one hour >80°C." Far from curing this deficiency, the secondary reference, Wehrmann, only reinforces this principle by conducting its own labeling reaction at 90°C for 30 minutes. A person of ordinary skill in the art reviewing these references would conclude that omitting the heating step would render the process "unsatisfactory for its intended purpose," and thus, there would be no motivation to make the modification.
The instant claims uses the open language “comprising” and does not exclude other method
steps, such as heating the reaction mixture.
The Examiner did not state modifying the references of Edwards and/or Wehrmann by omitting the heating step.
The reference of Edwards teaches of the synthesis of 64Cu-DOTA-TATE by diluting 64Cu with a labeling buffer (pH 5.5) and mixing with gentisic acid that encompasses mixing 64Cu and gentisic acid in an acidic aqueous solution of the instant claims. The reaction mixture of Edwards is heated but is also allowed to stand at room temperature for 24 hours that encompasses allowing the reaction solution to proceed at ambient temperature for at least 10 minutes of the instant claims.
The reference of Edwards does not state that the radiolabeling reaction does not continue during the 24 hour room temperature step and therefore, further radiolabeling may occur during this 24 hour time period at room temperature.
Applicant asserts that based on the clear teachings of both Edwards and Wehrmann, a POSITA
would have expected a room-temperature reaction to fail or proceed with impractically low yields. The discovery that 64Cu-DOTA-TATE can be successfully synthesized at high yields (>95%) in just 10 minutes at ambient temperature is a surprising and unexpected result that runs contrary to the established knowledge in the art.
The instant claims uses the open language “comprising” and does not exclude other method steps, such as heating the reaction mixture.
Also, the instant claims do not recite radiochemical yields, purities and/or a total reaction time. The instant claim 15 recites “reaction solution at ambient temperature for at least 10 minutes” which does not provide un upper limit to the time frame for the reaction and/or exclude any prior or subsequent method steps of heating and therefore, the claims are not commensurate in scope.
The arguments of counsel cannot take the place of evidence in the record. Examples of attorney statements are not evidence and must be supported by an appropriate affidavit or declaration include statements regarding unexpected results. MPEP § 716.01 (c).
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 15-19 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Edwards et al. (Proc. SPIE Vol. 6097, 609703-1 to 609703-8) in view of Wehrmann et al. (Cancer Biother. Radiopharm., 2007, 22, 406-416) as stated in the office action mailed 4/21/25.
Applicant asserts that the combination of Edwards and Wehrmann do not merely fail to suggest
the claimed invention; the references, both individually and in combination, actively discourage a person of ordinary skill in the art from attempting the claimed method.
The instant claims uses the open language “comprising” and does not exclude other method steps, such as heating the reaction mixture.
The reference of Wehrmann was used to specifically teach of the use of sodium acetate buffer (pH 5.5) for the method radiolabeling DOTA-peptides with 177Lu in the presence of gentisic acid.
The reference of Edwards teaches of the synthesis of 64Cu-DOTATATE stated above.
At the time of the invention, it would have been obvious to one of ordinary skill in the art to
substitute the ammonium acetate buffer of Edwards et al. for the sodium acetate buffer of Wehrmann et al. as they both provide the pH of 5.5 for radiolabeling of radioisotopes 64Cu and/or 177Lu with DOTA and the substitution of one known buffer for another analogous buffer is predictable as they are interchangeable for radiolabeling DOTA chelator with 64Cu and/or 177Lu and provide an analogous pH solution.
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 15-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 10,383,961B2 in view of Edwards et al. (Proc. SPIE Vol. 6097, 609703-1 to 609703-8) as stated in the office action mailed 4/21/25.
Claims 15-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,160,888B2 in view of Edwards et al. (Proc. SPIE Vol. 6097, 609703-1 to 609703-8) as stated in the office action mailed 4/21/25.
Claims 15-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 10,159,759B2 in view of Edwards et al. (Proc. SPIE Vol. 6097, 609703-1 to 609703-8) and (Cancer Biother. Radiopharm., 2007, 22, 406-416) as stated in the office action mailed 4/21/25.
Applicant asserts that they will consider filing a terminal disclaimers upon the indication of allowable subject matter.
The rejection is maintained.
Conclusion
No claims are allowed at this time.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MELISSA JEAN PERREIRA whose telephone number is (571)272-1354. The examiner can normally be reached M9-3, T9-3, W9-3, Th9-2, F9-2.
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/MELISSA J PERREIRA/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618