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 .
Drawings
The drawings are objected to because at least one drawing submitted in file is in color without granted petition to accept color drawings.
Appropriate correction is required.
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.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Specification
The abstract of the disclosure is objected to because it is too short in length (18 words). Applicant is reminded of the proper language and format for an abstract of the disclosure. The abstract should be in narrative form and generally be limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Appropriate correction is required.
The disclosure is objected to because of the following informalities:
Throughout the specification, the nonproprietary generic name of the biological agent “ofatumumab” is capitalized inconsistently, appearing arbitrarily as both uppercase “Ofatumumab” and lowercase “ofatumumab.” The arbitrary mixing of uppercase and lowercase letters across the specification creates ambiguity as to whether Applicant intends to attribute different technical meanings or limitations to these terms. To overcome this objection, Applicant is required to amend the specification to ensure the nomenclature of the agent is fully harmonize and unified throughout.
On page 4, line 8, “FIG. 9(A-C)” should read “FIG. 9(A-D).”
Appropriate correction is required.
Claim Objections
Throughout claims, the nonproprietary generic name of the biological agent “ofatumumab” is capitalized inconsistently, appearing arbitrarily as both uppercase “Ofatumumab” and lowercase “ofatumumab.” The arbitrary mixing of uppercase and lowercase letters within and across the claims creates ambiguity as to whether Applicant intends to attribute different technical meanings or limitations to these terms. To overcome this objection, Applicant is required to amend the claims to ensure the nomenclature of the agent is fully harmonize and unified throughout.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 1-4, 6, 7, 11, 13-15, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Longtine et al. (The Journal of Nuclear Medicine, 2020; cited on IDS filed December 4, 2024).
Regarding claims 1-4, 7, and 13-15, Longtine 2020 discloses a radioimmunotherapy method for treating non-Hodgkins lymphoma (NHL) (disseminated human lymphoma) using 89Zr-labeled ofatumumab (Ofa) and 225AC-labeled Ofa (page 1, ¶ 1). Longtine 2020 discloses that Ofa is a fully human anti-CD20 antibody which effectively targets lymphoma (CD20 disease) (page 1, ¶ 1). Longtine 2020 discloses that 89Zr-Ofa and 225AC-Ofa can form a theranostic (imaging and therapeutic) pair (a combination of 89Zr-Ofa and 225AC-Ofa) for NHL patients (page 2, ¶3).
Regarding claims 6, 11, and 20, Longtine 2020 discloses that subject can be injected IV (intravenously) with 89Zr-Ofa or 225AC-Ofa (page 1, ¶ 2 – page 2, ¶1).
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.
Claims 1-8, 10, 11, 13-16, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Longtine et al. (The Journal of Nuclear Medicine, 2020; cited on IDS filed December 4, 2024) in view of Hrick et al. (The National Academies Press, 2007; cited on PTO-892).
Regarding claims 1-4, 7, and 13-15, as discussed above, Longtine 2020 discloses a radioimmunotherapy method for treating non-Hodgkins lymphoma (NHL) (disseminated human lymphoma) using 89Zr-labeled ofatumumab (Ofa) and 225AC-labeled Ofa (page 1, ¶ 1). Longtine 2020 discloses that Ofa is a fully human anti-CD20 antibody which effectively targets lymphoma (CD20 disease) (page 1, ¶ 1). Longtine 2020 discloses that 89Zr-Ofa and 225AC-Ofa can form a theranostic (imaging and therapeutic)) pair (a combination of 89Zr-Ofa and 225AC-Ofa) for NHL patients (page 2, ¶3). Regarding claims 6, 11, and 20, as discussed above, Longtine 2020 discloses that subject can be injected IV (intravenously) with 89Zr-Ofa or 225AC-Ofa (page 1, ¶ 2 – page 2, ¶1).
Regarding claims 5, 8, and 16, Longtine 2020 does not disclose further administration to the subject of at least one pre-dose of unlabeled ofatumumab antibody prior to applying the theranostic treatment. Regarding claim 10, Longtine 2020 does not disclose administering the 225AC-Ofa and the 89Zr-Ofa sequentially to the subject in separate doses.
Hrick discloses a regimen for treating a lymphoma patient using a radioimmunotherapy agent that targets the CD20 antigen (page 63, ¶ 1 – page 64, ¶ 1). Hrick discloses that a patient can initially receive a dose of nonradioactive antibody intravenously, followed by an infusion of a monoclonal antibody labeled with a gamma-emitting radionuclide for trace imaging, and after imaging study, the patient can be administered a therapeutic dose of a monoclonal antibody radiolabeled with a beta-emitting radionuclide (page 63, ¶ 1 – page 64, ¶ 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the treatment regimen of Longtine 2020 by administering unlabeled Ofa, 89Zr-Ofa, and 225AC-Ofa in separate, sequential doses to treat NHL more effectively. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Hrick teaches an effective regimen strategy using a CD20-targeting agent for theranostic radioimmunotherapy of lymphoma. Further, a person of ordinary skill in the art would have been motivated to administer a pre-dose of unlabeled antibody before the theranostic treatment in order to increase targeting efficiency and reduce non-specific radiation toxicity. Additionally, a person of ordinary skill in the art would have been motivated to administer the diagnostic agent before or after the therapeutic agent in separate doses in order to verify the target biodistribution prior to radiotherapy, or in order to monitor the treatment effect after radiotherapy. It would have been customary for a person of ordinary skill in the art to optimize the treatment regimen according to the patient’s condition and the clinical purpose in order to maximize efficacy and minimize side effects.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Longtine et al. (The Journal of Nuclear Medicine, 2020; cited on IDS filed December 4, 2024) in view of Ling et al. (Pharmaceutics, 2022; cited on PTO-892).
Longtine 2020 is discussed above.
Longtine 2020 does not disclose administering the 225AC-Ofa and the 89Zr-Ofa simultaneously to the subject in a combined dose.
Ling discloses beta and alpha radionuclide therapy for the treatment of prostate cancer (abstract). Ling discloses that both radioligands targeting PSMA (prostate-specific membrane antigen) epitopes, such as 225Ac-PSMA and 177Lu-PSMA, can be administered simultaneously (page 9, ¶ 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the treatment regimen of Longtine 2020 by administering 225AC-Ofa and 89Zr-Ofa simultaneously in a combined dose to treat NHL more efficiently. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Ling teaches different radiolabeled antibodies can be administered simultaneously in a combined dose. Further, a person of ordinary skill in the art would have been motivated to administer theranostic agents simultaneously in order to eliminate the discrepancy between diagnostic and therapeutic bodily kinetics, and streamline clinical workflows. It would have been customary for a person of ordinary skill in the art to optimize the treatment regimen according to the patient’s condition and the clinical purpose in order to maximize efficacy and minimize side effects.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Longtine et al. (The Journal of Nuclear Medicine, 2020; cited on IDS filed December 4, 2024) in view of Castillo et al. (Expert Opinion on Investigational Drugs, 2009; cited on PTO-892).
Longtine 2020 is discussed above.
Longtine 2020 does not disclose that the CD20 disease is multiple sclerosis (MS).
Castillo discloses that Ofa is a safe and efficacious anti-CD20 antibody that can be used for the treatment of aggressive lymphoma and MS (abstract).
It would have been obvious to a person of ordinary skill in the art before the effective
filing date of the claimed invention to utilize the method of Longtine 2020 to treat a patient with MS. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Castillo teaches Ofa can be used for the treatment of lymphoma and MS. Castillo teaches that lymphoma and MS are art recognized equivalents as CD20 diseases and it is obvious to substitute one art recognized equivalent for another absent evidence of unexpected results. Further, a person of ordinary skill in the art would have been motivated to utilize the method for treating MS in order to expand the applications of the method.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Longtine et al. (The Journal of Nuclear Medicine, 2020; cited on IDS filed December 4, 2024) in view of Longtine et al. (The Journal of Nuclear Medicine, 2021; cited on PTO-892).
Longtine 2020 is discussed above.
Longtine 2020 does not disclose administration of 177Lu-Ofa
Longtine 2021 discloses that radioimmunotherapy method for treating NHL using 89Zr-Ofa and 177Lu-Ofa (page 1, ¶ 1). Longtine 2021 discloses that 89Zr-Ofa and 177Lu -Ofa can form a theranostic (imaging and therapeutic) pair for NHL patients (page 2, ¶3).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Longtine 2020 by utilizing 177Lu-Ofa in addition to the combination of 225AC-Ofa and 89Zr-Ofa in order to treat NHL more effectively. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Longtine 2021 teaches that 177Lu-Ofa can be used with 89Zr-Ofa as a theranostic agent for NHL treatment. Further, a person of ordinary skill in the art would have been motivated to utilize multiple radionuclides (having different decay profiles, particle ranges, and primary clinical utilities) attached to the same targeting molecules, in order to maximize tumor coverage in treating complex tumors and achieve advanced theranostics.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Longtine 2020 and Longtine 2021 as applied to claim 17 above, and further in view of Ling et al. (Pharmaceutics, 2022; cited on PTO-892).
Longtine 2020 and Longtine 2021 are discussed above.
Neither Longtine 2020 nor Longtine 2021 discloses administering 177Lu-Ofa, 225AC-Ofa, and 89Zr-Ofa simultaneously to the subject in a combined dose.
As discussed above, Ling discloses beta and alpha radionuclide therapy for the treatment of prostate cancer (abstract). Ling discloses that both radioligands targeting PSMA (prostate-specific membrane antigen) epitopes, such as 225Ac-PSMA and 177Lu-PSMA, can be administered simultaneously (page 9, ¶ 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the treatment regimen of Longtine 2020 and Longtine 2021 by administering 177Lu-Ofa, 225AC-Ofa, and 89Zr-Ofa simultaneously in a combined dose to treat NHL more efficiently. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Ling teaches different radiolabeled antibodies can be administered simultaneously in a combined dose. Further, a person of ordinary skill in the art would have been motivated to administer theranostic agents simultaneously in order to eliminate the discrepancy between diagnostic and therapeutic bodily kinetics, and streamline clinical workflows. It would have been customary for a person of ordinary skill in the art to optimize the treatment regimen according to the patient’s condition and the clinical purpose in order to maximize efficacy and minimize side effects.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Longtine 2020 and Longtine 2021 as applied to claim 17 above, and further in view of Hrick et al. (The National Academies Press, 2007; cited on PTO-892).
Longtine 2020 and Longtine 2021 are discussed above.
Neither Longtine 2020 nor Longtine 2021 discloses administering 177Lu-Ofa, 225AC-Ofa, and 89Zr-Ofa sequentially to the subject in separate doses.
As discussed above, Hrick discloses a regimen for treating a lymphoma patient using a radioimmunotherapy agent that targets the CD20 antigen (page 63, ¶ 1 – page 64, ¶ 1). Hrick discloses that a patient can receive an infusion of a monoclonal antibody labeled with a gamma-emitting radionuclide for trace imaging, and after imaging study, the patient is administered a therapeutic dose of a monoclonal antibody radiolabeled with a beta-emitting radionuclide (page 63, ¶ 1 – page 64, ¶ 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the treatment regimen of Longtine 2020 and Longtine 2021 by administering 177Lu-Ofa, 225AC-Ofa, and 89Zr-Ofa in separate, sequential doses to treat NHL more effectively. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Hrick teaches the theranostic agents can be administered sequentially in separate doses. Further, a person of ordinary skill in the art would have been motivated to administer different theranostic agents in different orders in order to achieve patient-specific dosimetry. It would have been customary for a person of ordinary skill in the art to optimize the treatment regimen according to the patient’s condition and the clinical purpose in order to maximize efficacy and minimize side effects.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JONG HWAN BAEK whose telephone number is (571)272-0670. The examiner can normally be reached Mon - Thu, 9 am - 3 pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael G 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.
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/JONG HWAN BAEK/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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