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. Applicant’s amendment filed on December 16, 2025 is acknowledged.
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Claims 52, 63-65, 68, 69, and 70 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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. Once again, the disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code, e.g. on page 35 of the specification as filed. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Applicant acknowledged Examiner’s objection to the specification regarding contains an embedded hyperlink and/or other form of browser-executable code but failed to amend the instant specification to the delete contains an embedded hyperlink and/or other form of browser-executable code. As such, the objection to the specification is maintained.
4. In view of applicant’s amendment, following rejections are set forth.
5. 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.
6. 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 are 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.
Ho et al. teach an anti-prostate specific membrane antigen (PSMA) antibody having identical six CDRs, and a VH (including three CDRs and FR region) that is 96.5% identical to the instantly claimed VH of SEQ ID NO:4 (see sequence alignments provided in the previous Office Action mailed on July 15, 2025.
Ho et al. further teaches that the antibody is conjugated to a radioimmunotherapy agent against prostate cancer including gamma emitting isotopes Indium 111 and Lutetium 177 (e.g. see [0007]). Ho et al. teaches a pharmaceutical composition comprising the anti-PSMA antibody (e.g. see [0014]). Ho et al. teach that the PSMA is a cell-surface biomarker that is associated with prostate cancer and anti-PSMA antibody is useful as imaging agent for detection and imaging of prostate cancer in soft tissue (e.g. see [0003] and [0007])
The reference teachings differ from the instant invention by not describing amino acid substitutions in the Fc region.
Yurkovetskiy et al. teach amino acid substitutions H310A and H435Q in the Fc region of IgG antibody results in shorten half-life of the antibody for improved imaging purposes (e.g. see [1008]. Yurkovetskiy et al. teach human IgG1 (e.g. see [1008]).
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 into the anti-PSMA antibody disclosed in Ho 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 Ho et al. teach anti-PSMA antibody binds PSMA antigen, a biomarker associated with prostate cancer, Yurkovetskiy et al. teach substitutions of H310A and H435Q in the Fc region are known to have shorten half-life and improved imaging effect. As such, introducing the well known beneficial substitutions H310A and H435Q into the Fc region of the anti-PSMA antibody disclosed by Ho 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 Ho teaches anti-PSMA minibodies J591 cys-diabodies without heavy chain constant region, and Ho also teach anti-PSMA minibodies comprising scFv that binds PSMA and human IgG CH3. Thus, applicant asserts that Ho’s antibodies do not have a CH2 containing amino acid residue I253 and H310, and some minibodies in Ho also does not have CH3 thus without H433 and H435. Applicant asserts that Ho teaches that the minibodies and cys-diabodies were developed for their improved pharmacodynamic properties for in vivo imagining and biodistribution over full length antibodies. Thus, applicant asserts there is no motivation from Ho to use the full length antibody, thus, no motivation to modify the Fc region in positions I253, H310, H433, and H435. Applicant further argues Leuschner et al. teaches anti-PSMA antibody conjugate but does not provide any teaching or guidance in relation to reducing serum half-life by modifying the recited positions in the Fc region. Applicant admits that Yurkovetskiy teaches H310/H435Q mutations in relation to a diagnostic produce but also teach that the mutations appear to have been undesirable.
Applicant states:
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Therefore, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
Contrary to applicant’s arguments that Ho only teach minibodies not full length anti-PSMA antibody, note that a prior art reference must be considered in its entirety, see MPEP 2141.02. Here, the teachings of Ho is not limited to minibodies. Rather, Ho specifically teach that full-length anti-PSMA antibody J591 (having identical CDRs to the instantly recited CDRs in claim 45) is deimmunized and being developed as a potential radioimmunotherapy agent against prostate cancer, and phase I clinical trial demonstrated excellent targeting to metastatic sites, lack of immunogenicity, well-tolerated for multiple doses, and specific targeting of tumor neovasculature of advanced solid tumors (e.g. see [0007]). Thus, Ho clearly teaches full length anti-PSMA antibody. In addition, Ho also teach minibody comprising scFc (having identical CDR sequences and VH sequence with the instantly claimed antibody), a hinge, and a human IgG CH3 region which includes H433.
Further, contrary to applicant’s assertion, the instant claims when given the broadest reasonable interpretation, read on an antibody comprising a heavy chain constant region wherein one or more positions at H310, H433, H435, and I253 are mutated. The instant claims do not recite full-length antibody nor do they recite CH2 and CH3.
Therefore, applicant’s arguments that Ho does not teach full length anti-PSMA antibody are not found persuasive.
Furthermore, Yurkovetskiy teaches that Double Mutant H310A and H435Q were known in the art to have the benefit of shorten the half-life of the antibody fragment for improved imaging purposes (e.g. see [1008]).
Given that Ho teaches well known humanized full-length anti-PSMA antibody shows excellent targeting to metastatic sites and is well-tolerated in human, and useful as imaging agent for detection and imaging of prostate cancer in soft tissue , and in view of the teachings of Yurkovetskiy regarding the benefit of double mutant H310A and H435A in the Fc regio of IgG antibody in shortening half-life of the antibody for imaging, an ordinary skill in the art would have been motivated to modify the well-known anti-PSMA antibody in the Fc region in H310A and H435Q for imaging prostate cancer. The shorten half-life of the full length anti-PSMA antibody would be expected to be beneficial in that it will be removed from the body as soon as imagine of prostate cancer was done.
As such, applicant’s arguments have not been found persuasive.
7. Claims 45, 46, 48, 50, 51, 53, 61, 62, 66, 67, and newly added claim 71 are rejected under 35 U.S.C. 103 as being unpatentable over Jones et al. (US 2019/0144562) in view of Yurkovetskiy et al. (US 2015/0104407).
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 shown 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]).
The reference teachings differ from the instant invention by not describing amino acid substitutions in the Fc region.
Yurkovetskiy et al. teach amino acid substitutions H310A and H435Q in the Fc region of IgG antibody results in shorten half-life of the antibody for improved imaging purposes (e.g. see [1008]. Yurkovetskiy et al. teach human IgG1 (e.g. see [1008]).
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 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, Yurkovetskiy et al. teach H310A and H435Q double substitutions in the Fc region of an antibody exhibits shorten half-life and improved imaging effect. 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 has not disputed that Jones et al. teach identical anti-PSMA antibody sequences as the instantly recited sequences but argues that Jones et al. do not teach modification in the constant region of the antibody. Even though Jones et al. teach the same VH and VL as the instantly recited antibody, applicant asserts that Jones et al. primarily concerned with maintaining native conformation and reducing immunogenicity while the instant antibody (identical in VH and VL to the antibody disclosed in Jones et al) has strong binding, low immunogenicity and good stability. Applicant further asserts Jones et al. teach shorter half-life negatively correlates with anti-tumor activity. Applicant asserts that the only advantages provided by the prior art is reduced radiotoxicity. Applicant states:
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Applicant asserts that since the independent claim is nonobvious, the dependent claims would be nonobvious too. Thus, applicant argues the rejection should be withdrawn.
This is not found persuasive for following reasons:
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Here, the question is not whether Jones et al. teach the instant invention. Rather, the question is whether the teachings of Jones et al. in view of Yurkovetskiy et al. would render the instant claims obvious.
Jones et al. teach an anti-PSMA antibody having six CDRs, VH, and VL that are 100% identical to the instantly claimed antibody, and further teach that the antibody can be used for detection (e.g. see [0079]-[0081). Yurkovetskiy et al. teach amino acid substitutions H310A and H435Q in the Fc region of IgG antibody results in shorten half-life of the antibody for improved imaging purposes. Thus, combining the teachings of Jones et al. with Yurkovetskiy et al. would have yielded an anti-PSMA antibody having H310A and H435Q substitutions in the Fc region that are useful for imaging purposes. Such antibody would be desirable to one of ordinary skill in the art to use for diagnosing prostate cancer because the antibody would be expected to detect PSMA in prostate cancer and having a shorter half life and be removed once detection was done.
Therefore, 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. 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.
10. 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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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