DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 29, 2026 has been entered.
Claims 1-44, 47, and 54-60 have been canceled.
Claim 71 have been added.
Claims 45, 46, 48-53, and 61-71 are pending.
Claims 52, 63-65, 68, 69, and 70 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 16, 2-25.
Claims 45, 46, 48-51, 53, 61, 62, 66, 67, and 71 are currently under consideration as they read on the elected invention described above.
3. In view of applicant’s amendment, following rejections are set forth.
4. 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.
5. 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.
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.
6. Claims 45, 46, 48, 50, 51, 53, 61, 62, 66, and 67 stand rejected under 35 U.S.C. 103 as being unpatentable over Ho et al. (WO 2011/069019) in view of Yurkovetskiy et al. (US 2015/0104407) for the reasons of record.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant asserts that the amended independent claim 45 render the rejection moot because claim 71 was not included in this rejection. As such, applicant asserts that Ho et al. do not teach VH and VL that is identical to the instantly recited antibody and therefore, the rejection should be withdrawn.
This is not found persuasive for following reasons:
In contrast to applicant’s reliance on claim amendment, note the claims filed together with the filing of RCE on May 29, 2026 do not appear to be amended when compared to the previously filed claims on December 16, 2025.
The independent claim 45 is still drawn to an anti-PSMA antibody with reduced FcRn binding affinity comprising a heavy chain constant region comprising one or more amino acid substitutions in positions H310, H433, H435, and I253, a VH CDRs 1-3 of SEQ ID NO:s 1, 2, and 3, and a VL CDRs 1-3 of SEQ ID NOs: 33-35, respectively.
Independent claim 45 does not require the complete VH and VL, only six CDRs which are identical to the anti-PSMA antibody disclosed in Ho et al. (see sequence alignments provided in Office Action mailed on July 15, 2025).
In addition, instant dependent claim 46 further limits the anti-PSMA antibody to have a VH that is at least about 95% identical to SEQ ID NO:4 or a VL at least about 95% identical to SEQ ID NO:36. Ho et al. discloses a VH that is 96.5% identical to the instant SEQ ID NO:4 (see sequence alignments provided in the previous Office Action mailed on July 15, 2025).
Given that no claim amendment has been made, the rejection is maintained for the reasons of record.
7. Claims 45, 46, 48, 50, 51, 53, 61, 62, 66, 67, and 71 stand rejected under 35 U.S.C. 103 as being unpatentable over Jones et al. (US 2019/0144562) in view of Kenanova et al. (Cancer Res. 2005 65:2:622-631).
Jones et al. teach an anti-PSMA antibody having six CDRs, VH, and VL that is 100% identical to the instantly claimed antibody, see sequence alignment provided in the Office Action mailed on July 15, 2025.
Jones et al. teach that the antibody is humanized and conjugated to a drug for use in treatment or diagnosis of prostate cancer (e.g. see [0001]). Jones et al. teach anti-PSMA antibody conjugated to radiolabel such as Lutetium 177 (e.g. see [0076]).
Jones et al. further teach that the anti-PSMA antibody can be used to treat cancer such as prostate cancer and diagnose cancer having PSMA antigen such as imaging method to visualize expression of PSMA (e.g. see [0219]-[0221]).
The reference teachings differ from the instant invention by not describing amino acid substitutions in one or more residues in H310, H433, H435, and I253 in the Fc region.
Kenanova et al. teach that monoclonal antibodies are known for their use in cancer treatment and imaging and beneficial features such as prolonged serum half-life of the native antibodies can be problematic when antibodies are conjugated to radionuclides or other toxic agents because such antibodies would remain in circulation for extended period of time causing significant irradiation and toxicity to normal organs (e.g. see Introduction in page 622).
Kenanova et al. teach anti-carcinoembryonic antigen (CEA) scFv (VL-linker-VH) joined to intact Fc region (CH2-CH3, crucial for prolonging the half-life) of human IgG1 via a hinge region behaves similarly to intact antibodies regarding serum persistence and tumor uptake (e.g. see right col. in page 622).
Kenanova et al. further teach residues I253 and H310 in CH2 domain and H435 in CH3 domain are known to be essential for FcRn binding and mutation in these residues correlates with reduced antibody half-life (e.g. see left col. in page 623).
Kenanova et al. teach scFv-Fc consisting amino acid substitutions H435Q, I253A, H310A, or H310A/H435Q bound antigen effectively as compared to the scFv-Fc with wild type Fc (see Discussion in left col. 1 in page 628) and H310A/H435Q double construct has the most accelerated serum clearance (e.g. see right col. in page 628).
Kenanova et al. teach H310A/H435Q mutant showed a superior ability to quickly localize to the tumor site and clear from the circulation, thus producing clear high-contrast images (e.g. see right col. in page 630).
It would thus be obvious to one of ordinary skill in the art at the time the instant invention was filed to introduce H310A and H435Q known to have reduced serum half life effect in an IgG antibody as disclosed by Kenanova et al. into the anti-PSMA antibody disclosed in Jones et al. in order to improve imaging prostate cancer in soft tissue. An ordinary skill in the art would have been motivated to do so, and have a reasonable expectation of success, since Jones et al. teach anti-PSMA antibody binds PSMA antigen, a biomarker associated with prostate cancer, Kenanova et al. teach H310A and H435Q double substitutions in the Fc region of an scFv-Fc antibody (having similar structure as the IgG antibody) showed a superior ability to quickly localize to the tumore site and clear from the circulation, producing clear high-contrast. As such, introducing the well-known beneficial substitutions H310A and H435Q into the Fc region of the anti-PSMA antibody disclosed by Jones et al. would have resulted in an anti-PSMA antibody with shorten serum half-life and improved effect in imaging prostate cancer.
Given that the prior art teaches Fc substitutions in human IgG1 Fc region, the prior art Fc variant having identical substitutions H310A and H435Q would inherently have the same amino acid sequences as the instantly claimed heavy chain constant region.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant argues that Jones et al. does not teach mutations in one or more positions in H310, H433, H435, and I253 with reduced FcRn binding affinity compared to a wild-type IgG. Applicant argues that Jones et al. emphasized strong PSMA binding, low immunogenicity, and good stability and desired to have the antibody recite in a native conformation for longer. Applicant asserts that Jones et al. imply it is advantageous that the antibody stability and longer residence in circulation which is opposed to the instant invention that directed to reduced serum half-life through Fc engineering. Applicant asserts that when Jones et al. discusses shorter half-life, it was about antibody conjugate as compared to unconjugated antibody. Thus, applicant asserts that there are no reasons to combine Jones’ anti-PSMA antibody with Yurkovetskiy teachings of H310A/H435Q substitution. Applicant also argues that Yurkovetskiy teaches sdFv-Fc trastuzumab polymer conjugate. This disclosure does not teach anti-PSMA antibody. Applicant acknowledges that Yurkovetskiy teaches that the known H310A/H435Q substitutions in Trastuzumab-scFv-Fc for shorter half-life for imaging purpose but teaches that the modifications were reverted back to the canonical IgG1 sequence, thus, applicant asserts that Yurkovetskiy does not considered H310A/H435Q to be desirable for polymer conjugation.
Applicant states:
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Furthermore, applicant argues that there is no reasonable expectation of success in combining the teachings of the references because it is not clear if incorporating H310A/H435Q into the anti-PSMA antibody would affect the antigen binding because Yurkovetskiy teaches H310A/H435Q substitutions in a different antibody. Neither reference teaches that an antibody with reduced serum half-life would maintain equivalent tumor accumulation and therapeutic efficacy.
Moreover, applicant asserts unexpected results as following:
In exhibit A (Lenzo et al. ASCO Gu 2025, reference on IDS) teaches 64Cu-TLX592 antibody used in the CUPID trial is an anti-PSMA antibody comprising double substitutions H310A/H435Q and VH+VL. The phase I clinical trial 11 subjects with advanced prostate cancer were administered the antibody conjugate and displayed significant faster blood clearance than unmodified antibody, yet also exhibit similar on-target and off-target biodistribution at 20 hours post-administration including bone lesion uptake, and no serious adverse events were observed. Applicant asserts that this phase I clinical trial corroborated with the Examples 4 and 5 in instant application as-filed in that tumor:blood ratio for FcRn modified antibody is approximately 200-fold higher than unmodified antibody at 120 hours but tumor loading is not statistically different despite the significant reduced serum half-life. Thus, applicant asserts that these surprising results were not teach or suggested by the references.
As such, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
In contrast to applicant’s assertion based on unexpected and surprising results relying upon the phase I clinical data and Examples 4 and 5 in the instant specification as-filed, note that these results are not commensurate in scope with the instant claims. This is because the data in Exhibit A and Examples 4 and 5 in the instant specification were based on full length anti-PSMA antibody IgG1 with H310A and H435Q substitutions in the Fc region while the instant claims encompass an anti-PSMA antibody comprising six CDRs and “one or more amino acid residues at positions His310, His 433, His435, and Ile 253” which do not recite the specific amino acid substitutions in these positions.
Further, in response to applicant’s assertion of unexpected results, note that the mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). Here, given that the anti-PSMA antibody was known in the art to be useful in prostate cancer imagine as disclosed by Jones et al. and in view of the teachings of Kenanova et al. regarding the superior ability to quickly localize to the tumor site and clear from the circulation, an ordinary skill in the art would have been able to combine the teachings of the references to produce an anti-PSMA antibody with H310A/H435Q substitutions in the Fc region for best tumor images and rapid clearing from the circulation to reduce side effect. Such anti-PSMA antibody with H310A/H435Q substitutions would inherently/intrinsically have the same functions including tumor loading that is not statistically different despite the significant reduced serum half-life.
Furthermore, it was known in the art that H310A/H435Q substitutions showed superior ability to localize to the tumor site ant clear from circulation, single substitution H435Q shows slow clearing and I253A/H310A shows intermediate clearing relative to H310A/H435Q (Kenanova et al., see left col. in page 630, in particular). Therefore, it is not likely that the unexpected and surprising results observed in data from H310A/H435Q substitutions would also be the same in H435Q.
Moreover, in contrast to applicant’s assertion that one would not know if incorporating H310A/H435Q into the anti-PSMA antibody would affect the antigen binding, note that it was well-known in the art at the time the instant invention was filed that mutations in the Fc region in one human IgG1 antibody is transferrable to the Fc region of another human IgG1 antibody with different antigen specificity. For example, Kenanova et al. teach it was shown by other scientists such as Ward et al. that mutations in Ile253, His310 and His435 correlates with reduced antibody half-life (e.g. see left col. in page 623). This is consistent with the human IgG1 anti-CEA antibody shown by Kenonova et al. (see detailed discussion above). Therefore, one of skill in the art would understand H310A/H435Q substitution disclosed by Kenanova et al. would be beneficial when incorporated into the anti-PSMA antibody for prostate cancer imaging purpose.
Simply because the formation and properties of a new compound must be verified through testing does not mean that the compound satisfies the test for patentability “since the expectation of success need only be reasonable, not absolute”); In re Merck Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986) (“obviousness does not require absolute predictability.”).
As such, applicant’s arguments have not been found persuasive.
8. Claim 49 remains to be objected to as being dependent upon a rejected base claim 45, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHUN W DAHLE/Primary Examiner, Art Unit 1641
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