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 .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 10/29/2024 is acknowledged.
Claim 8-15 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II-III, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/29/2024.
While the Applicant has not elected a species at this time and an election is not required at this stage, when the withdrawn claims are examined, the Applicant will be required to make a species election in accordance with the restriction requirement.
Status of Claims
Withdrawn: 8-15
Cancelled: 2-4, 6
Examined Herein: 1, 5, 7
Priority
Priority to PRO 62/823,411 filed on 3/25/2019 and PCT/US2020/024719 filed on 3/25/2020 is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/24/2021 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings filed on 9/24/2021 are accepted.
Withdrawn Rejections
All rejections of claims 2-4 and 6 are hereby withdrawn. The cancellation of these claims moots the rejections.
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 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Marko (Optimization of Tumor-Imaging and Therapeutic Potential of Near-Infrared Multifunctional Agents, and Targeted Polyacrylamide Theranostic Nanoplatforms, 2016, University Of New York At Buffalo Proquest Dissertations & Theses, 10163885).
With respect to claim 1, Marko discloses a compound having the following structure:
PNG
media_image1.png
315
224
media_image1.png
Greyscale
[Marko, Page 100, Figure 29; see also, Page 100, Figure 29]
wherein:
R” is I,
X is O,
n is 1, and
the dotted carbon is chiral and is R or S, thus meeting the limitations of claim 1.
With respect to claims 1 and 3, Marko discloses a compound having the following structure:
PNG
media_image2.png
241
194
media_image2.png
Greyscale
[Marko, Page 105, Figure 30]
wherein:
R” is 124I,
X is O,
n is 1, and
the dotted carbon is chiral and is R or S, thus meeting the limitations of claims 1 and 5.
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.
Claims 1, 5, and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Kozyrev (Synthesis, Photophysical and Electrochemistry of Near-IR Absorbing Bacteriochlorins Related to Bacteriochlorophyll a, 10/22/2012, The Journal of Organic Chemistry, 77:10260-10271), in view of Srivatsan (In Vitro Cellular Uptake and Dimerization of Signal Transducer and Activator of Transcription-3 (STAT3) Identify the Photosensitizing and Imaging-Potential of Isomeric Photosensitizers Derived from Chlorophyll-a and Bacteriochlorophyll-a, 8/15/2011, Journal of Medicinal Chemistry, 54:6859-6873).
With respect to claims 1 and 5, Kozyrev discloses the following bacteriopyropheophorbide comprising a methyl ester substituent:
PNG
media_image3.png
219
262
media_image3.png
Greyscale
[Kozyrev, Page 10263, Compound 14, Scheme 3]
Kozyrev does not disclose the compound comprises the following substituent:
PNG
media_image4.png
122
156
media_image4.png
Greyscale
wherein,
R” is I or 124I.
However, with respect to claims 1 and 5, Srivatsan discloses the following bacteriopyropheophorbide:
PNG
media_image5.png
276
214
media_image5.png
Greyscale
[Srivatsan, Page 6860, Scheme 1]
wherein,
R” is I or 124I
X is O
n is 1, and
the dotted carbon is chiral and is R or S.
With respect to claim 7, Srivatsan discloses a composition comprising a 124I-labeled photosensitizer and a pharmaceutically acceptable carrier, 10% ethanol/saline. [Srivatsan, Page 6871, Col. 1, Paragraph 3]
Moreover, Srivatsan discloses a synthetic approach for replacing the methyl ester substituent of a bacteriopyropheophorbide-a compound with 124I-Iodobenzyloxyethyl.
PNG
media_image6.png
884
1003
media_image6.png
Greyscale
[Srivatsan, Page 6863, Scheme 3]
Modifying the compound disclosed by Kozyrev by replacing the methyl ester substituent with 1241-iodobenzyloxyethyl results in the compound of claim 1 and 5.
Further modifying the compound disclosed by Kozyrev by combining the compound with a pharmaceutically acceptable carrier results in the composition of claim 7.
It would be obvious to one of ordinary skill in the art to modify the compound disclosed by Kozyrev by replacing the methyl ester substituent with 1241-iodobenzyloxyethyl and have a reasonable expectation of success. Kozyrev discloses a bacteriopyropheophorbide comprising a methyl ester substituent. Srivatsan discloses a bacteriopyropheophorbide comprising a methyl ester substituent and a bacteriopyropheophorbide comprising a 1241-iodobenzyloxyethyl substituent. Srivatsan further discloses that the bacteriopyropheophorbide that comprises a methyl ester substituent may be converted into a bacteriopyropheophorbide comprising a 1241-iodobenzyloxyethyl substituent by replacing the methyl ester substituent with a 124I-iodobenzyloxyethyl substituent. Accordingly, Srivatsan discloses that a bacteriopyropheophorbide comprising a methylester substituent may be replaced with a 124I-iodobenzyloxyethyl substituent. Thus, the combined teachings of Kozyrev and Srivatsan reasonably suggest that the bacteriopyropheophorbide comprising a methylester substituent disclosed by Kozyrev may be replaced with a 124I-iodobenzyloxyethyl substituent. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II) In the present case, Srivatsan discloses that 1241-iodobenzyloxyethyl pyropheophorbide-a was found to be an effective PET/PDT imaging agent. [Srivatsan, Page 6861, Col. 1, Paragraph 2] Therefore, one would have been motivated by the expectation that the aforementioned modification would enable the compound disclosed by Kozyrev to be employed as an effective PET/PDT imaging agent.
It would be obvious to one of ordinary skill in the art to further modify the compound disclosed by Kozyrev and Srivatsan by combining it with a pharmaceutically acceptable carrier and to have a reasonable expectation of success. Kozyrev and Srivatsan disclose a 124I-labeled photosensitizer. Srivatsan discloses a composition comprising a 124I-labeled photosensitizer and a pharmaceutically acceptable carrier, 10% ethanol/saline. Accordingly, the combined teachings of Kozyrev and Srivatsan suggest the 124I-labeled photosensitizer disclosed by Kozyrev and Srivatsan may be present in a composition comprising a pharmaceutically acceptable carrier. Therefore, it is reasonable to expect that the compound disclosed by Kozyrev and Srivatsan may be further modified by combining it with a pharmaceutically acceptable carrier. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Srivatsan discloses that dissolving the 124I-labeled photosensitizer in 10% ethanol/saline solution enables its use in in vivo experiments. [Srivatsan, Page 6871, Col. 1, Paragraph 3] Therefore, one would have been motivated by the expectation that combining the compound disclosed by Kozyrev and Srivatsan with a pharmaceutically acceptable carrier would enable the compound to be used for in vivo experiments.
Response to Arguments
Applicant's arguments filed 6/15/2026 have been fully considered but they are not persuasive.
Applicant asserts, “Srivatsan disclosed iodinated and radio-iodinated photosensitizers derived from chlorophyll-a and bacteriochlorophyll-a. Srivatsan also states:
[s]everal considerations need to be made when designing selective radiolabeled drugs ... includ[ing] efficient drug delivery, optimization of relative accumulation of the drug at the target over nontarget sites, maximizing the residence time of the radioactivity at the target sites, and prevention of structural alteration of the drug. Because of the multiple parameters that must be considered, developing effective radiopharmaceuticals for combined imaging and therapy of cancer is a challenging undertaking that is not simply solved by attaching a radionuclide in any fashion to a nonradiolabeled targeting compound. Srivatsan at p. 6860, left column. This statement directly undercuts the Examiner's argument.
That is, one having ordinary skill in the art would not expect the instant claims to have the
observed PET imaging profiles presented in the instant application. The cited reference specifically states this is beyond mere substitution and is not expected.” [Remarks 6/15/2026, Page 5-6]
Applicant relies on Srivatsan's aforementioned statement to establish that a POSITA would not be motivated to modify the compound disclosed by Kozyrev by replacing the methyl ester substituent with 124I-Iodobenzyloxylethyl. As a result, Applicant contends one of ordinary skill in the art would not expect the claimed compounds to have the observed PET imaging profiles, thereby undermining the rejection of record. However, this argument is not persuasive.
The aforementioned statement refers to Srivatsan's finding that the position of the iodobenzyl group on porphyrin-based compounds affects efficacy in uptake, retention, internalization, and intracellular retention. Srivatsan essentially states that when developing effective radiopharmaceuticals for combined imaging and therapy of cancer, the position of the radionuclide on the targeting compound matters and cannot be placed arbitrarily. Accordingly, Srivatsan demonstrates that the positions at which an iodobenzyl group on porphyrin-based compounds is most effective (which is on the methyl ester). [Srivatsan, Page 6861, Figure 1] Importantly, the claimed rejection proposes modifying the compound disclosed by Kozyrev by replacing the methyl ester substituent with 124I-Iodobenzyloxylethyl at precisely that position. Applicant’s characterization of Srivatsan's statement is misplaced because Srivatsan does not teach that this modification is beyond mere substitution. Rather, Srivatsan states that this modification yields an effective imaging agent. Specifically, Srivatsan states "…for imaging, 72 h post injection for… compound PS 27 (data not shown) produced the best contrast…" [Srivatsan, Page 6867, Col. 1, Paragraph 1]
Furthermore, the nature of a prior art reference that teaches away is highly relevant and must be weighed in substance. A prior art reference does not teach away if the disclosure does not criticize, discredit, or otherwise discourage the claimed solution. MPEP 2145(X)(D)(1). Srivatsan makes the aforementioned statement in the "Introduction" section, which generally details relevant background information, the state of the art before the author's contribution, and then introduces the author's contribution. This approach makes it clear to the reader why the described findings are significant. Srivatsan's statement follows this framework precisely. Srivatsan states that developing effective radiopharmaceuticals for combined imaging and therapy of cancer is not simply solved by attaching a radionuclide in any fashion to a non-radiolabeled targeting compound. In the following paragraphs, Srivatsan introduces his contribution: developing porphyrin-based compounds for use as PET/PDT imaging agents by attaching 124I to a series of porphyrin-based compounds in a meticulous fashion. [Srivatsan, Page 6861, Paragraph 2-3] Therefore, Srivatsan does not, in general, criticize, discourage, or discredit developing effective radiopharmaceuticals for combined imaging and therapy of cancer by attaching a radionuclide to a non-radiolabeled targeting compound. Rather, Srivatsan's aforementioned statement condemns attaching a radionuclide to a non-radiolabeled targeting compound arbitrarily. However, Srivatsan does not attach the radiolabel without rhyme or reason, nor does the rejection of record propose doing so.
In fact, Srivatsan's disclosure is drawn to the very undertaking that Applicant claims his statement undercuts. A POSITA would not be discouraged from replacing the methyl ester substituent with 124I-Iodobenzyloxylethyl, simply because Srivatsan acknowledged that the position that a radiolabel is attached to nonradiolabeled targeting compounds is not an arbitrary undertaking. Especially considering that Srivatsan successfully and meticulously attached 124I to the porphyrin-based compound's methyl ester group to obtain PET/PDT imaging agents with successful PET imaging profiles.
Finally, if the challenge of developing effective radiopharmaceuticals for combined imaging and therapy of cancer were sufficient to convince a POSITA that radiolabeling a nonradiolabeled targeting compound is beyond mere substitution, then the reference's own author would not have succeeded in doing precisely that. Srivatsan did not use the aforementioned statement to justify abandoning the undertaking, and neither would a POSITA in view of Srivatsan’s disclosure.
Conclusion
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 KAILA A CRAIG whose telephone number is (703)756-4540. The examiner can normally be reached Monday-Friday 0800-1600.
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, Michael 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
Prosecution Insights