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 .
Response to Arguments
Applicant's arguments, filed June 8, 2026, have been fully considered but they are not deemed to be fully persuasive. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112 Improper dependency
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2-4 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 2 recites “each metallobacteriochlorin… is complexed to copper or manganese.” However, independent claim 1 has been amended to delete the limitation requiring the agent to be complexed to manganese and must be complexed to copper. Because claim 1 no longer contains or requires complexation with manganese, dependent claim 2 is broader than claim 1 from which it depends, creating an improper dependent structure. It is suggested that claim 2 be amended to delete “or manganese” to obviate this rejection.
The dependent claims fall therewith.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-3, 33, and 35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pitner et al. (US 2020 0009272; cited on IDS filed July 5, 2023).
This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed March 31, 2026 and those set forth herein.
Applicant argues that Pitner fails to teach every element of the claimed invention because Pitner fails to disclose any copper-complexed metallobacteriochlorin, metallochlorin, or derivative thereof as required by Claim 1. Applicant argues that Pitner generally states that bacteriochlorins can be complexed with metals such as copper, but such a generic disclosure does not identify any particular copper complex falling within the claim, nor does it disclose a photoacoustic imaging contrast agent comprising such a copper-complexed species. Applicant argues that one of skill in the art would need to pick and choose from among various metals mentioned by Pitner, including Zn, Cu, Pd, Ni, Fe and Co, to select copper without any other direction.
This argument is unpersuasive. As discussed in the Office Action mailed March 31, 2026, Pitner explicitly teaches Cu as a specific metal to be complexed with bacterochlorins (¶ 80). The list of metals provided in Pitner (Zn, Cu, Pd, Ni, Fe, and Co) is a small, limited number. A person of ordinary skill in the art would envisage the copper-complexed bacteriochlorin without undue experimentation. This is not a case of a generic disclosure requiring undue picking and choosing. Rather, it is a specific, literal disclosure of the claimed species. Further, these six elements (Zn, Cu, Pd, Ni, Fe, and Co) share highly similar coordination geometries. The elements are transition metals, except for Zinc, which is technically a post-transition metal despite its similarities. Substituting one highly similar metal for another within the same well-known macrocycle does not confer novelty. Because Pitner teaches a photoacoustic imaging agent comprising a metallobacteriochlorin and inherently teaches the same Cu-complexed bacteriochlorins of instant claims, the use of the Cu-complexed compound as a photoacoustic imaging contrast agent does not confer patentability. Further, discovering a new property or new use for a known compound does not confer novelty upon that compound itself because the compound is already part of the prior art. Accordingly, the claimed compound is anticipated and the rejection is maintained.
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 1-4, 33, 35, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Pitner et al. (US 2020 0009272; cited on IDS filed July 5, 2023) in view of Pucelik et al. (Coordination Chemistry Reviews, 2020; cited on IDS filed February 12, 2026).
This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed March 31, 2026 and those set forth herein.
Regarding new claim 40, Pitner discloses a compound of Formula IA
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(¶ 57). The compound of Formula IA and the compound (CuBC-2-PEG) of instant claim 40 share the same bacteriochlorin core structure. The substituent definition in ¶ 59 provides a broad list of permissible groups that cover all the functional groups present in the CuBC-2-PEG of instant claim 40. Specifically, Pitner discloses that R1, R2, and R5 can be H; R3 and R4 can be alkyl; R6 can be hydrophilic groups or linking groups; R7 can be ester; R8 can be H or alkoxy; and the compound can be metalated (¶ 59; ¶ 62). Pitner also discloses a water soluble metallobacteriochlorin such as
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(¶ 20; FIG. 7). Pitner discloses that Cu can be complexed with bacterochlorins (¶ 80) and that the solubilizing (hydrophilic) groups such as PEG chains can improve the biolabeling efficiency and bioconjugate stability (¶ 49). A person of ordinary skill in the art would have been motivated to utilize Cu as a complexed metal based on the specific requirements of the intended applications as a design choice. The water soluble metallobacteriochlorin of Pitner and the CuBC-2-PEG of instant claim 40 share the same bacteriochlorin core structure with various functional groups including PEG units. The water soluble metallobacteriochlorin of Pitner contains a functionalized phenyl-carboxylic acid tail at the bottom meso-position (R8), whereas the structure of the instant claim 40 has no bottom meso-tail (only H). However, Pitner already teaches that the R 8 can be H (¶ 59), and removing the bottom meso-tail constitutes a predictable and routine optimization in pharmaceutical compound design. Where bioconjugation to an antibody or peptide is not required, deleting this structurally burdensome link is a logical modification with a clear expectation of success to achieve a more streamlined, synthetically accessible, and stable standalone agent. The water soluble metallobacteriochlorin of Pitner has shorter PEG chains with eight repeating units, whereas the structure of the instant claim 40 possesses a longer PEG chain with twelve repeating units. A person of ordinary skill in the art would have been motivated to tune the number of PEG repeating units as a design choice according to the desired requirements of the specific applications. The repeating number of PEG unit is a clearly result-effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the number of the PEG repeating units such as twelve repeating units in order to best achieve the desired solubility profile, as the length of the PEG chain critically determines the hydrophilicity of the compound.
Applicant argues that the Office Action fails to establish a prima facie case of obviousness over Pitner in view of Pucelik because the Office has failed to identify a reason why a person of ordinary skill in the art would have made the specific modifications required to arrive at the compound of present claim1. Applicant argues that Pitner provides no motivation to make a copper-complexed bacteriochlorin for use in the present imaging contrast agents.
This argument is unpersuasive. As discussed above, Pitner teaches the compound of instant claim 1. As discussed in the Office Action mailed March 31, 2026, the combination of Pitner and Pucelik renders claim 4 obvious. A person of ordinary skill in the art would have been motivated to modify the contrast agent of Pitner to include Cu-complexed bacteriochlorin in addition to bacteriochlorins complexed with other metals in order to adjust the optical and redox properties of the agent. Specifically, Pucelik teaches that metallobacteriochlorins can be complexed with various metals, and that the introduction of these metal ions determines the characteristics of the resulting contrast agent, enabling the tuning of its optical and redox properties. Because both references operate within the closely related technical field of diagnostic imaging agents, a person of ordinary skill in the art would naturally look to Pucelik to optimize the performance parameters of Pitner’s composition for photoacoustic imaging. Further, a person of ordinary skill in the art would have been motivated to optimize the combination of different metal-complexed metallobacteriochlorins based on the specific requirements of the intended application. Such routine optimization represents nothing more than the predictable selection of known materials from a finite pool of options to achieved a predictable result.
Applicant argues that the unexpected results obtained by Applicant demonstrate that the claimed copper-complexed metallobacteriochlorin contrast agents would not have been obvious. Applicant argues that Example 4 and Figure 10 demonstrates unexpected optical performance for the claimed copper-complexed agents. Applicant argues that the data show that the claimed copper- complexed bacteriochlorins provide a more intense and more narrowly defined absorption profile than the conventional comparator ICG. Applicant argues that nothing in Pitner or Pucelik suggests that improved signal generation and more precise wavelength discrimination could be obtained by selecting copper-complexed bacteriochlorins.
This argument is unpersuasive. Applicant’s assertions of unexpected results fail to satisfy the requisite legal criteria established under MPEP § 716.02. Objective evidence of unexpected results must be supported by appropriate evidentiary showing, direct comparative data, and must be commensurate in scope with the claims. Applicant has failed to meet this burden based on the following criteria.
First, the alleged results are predictable, not truly unexpected. To establish unexpected results, the performance or enhancement must significantly exceed what a person having ordinary skill in the art would have reasonably anticipated. Merely showing that a specific Cu-complexed macrocyclic bacteriochlorin dye showed better absorption with narrower peak compared to ICG or another specific Cu-complexed macrocyclic bacteriochlorin dye is predictable difference in kind, not an unexpected result. As discussed above, Pucelik teaches that metallobacteriochlorins can be complexed with various metals, and that the introduction of these metal ions determines the characteristics of the resulting contrast agent, enabling the tuning of its optical and redox properties. A different characteristic of absorbance between metal-complexed macrocyclic bacteriochlorin dye and ICG represents a predictable quantitative difference (a matter of degree) rather than an entirely new, qualitative chemical mechanism that was un-anticipatable by the prior art.
Second, Applicant fails to provide direct comparison with the closest prior art (Pitner and Pucelik individually or in a baseline combination). The evidence of unexpected results must involve a direct, side-by-side comparison between the claimed invention and the closest prior art. ICG is not the closest prior art. Applicant must compare the claimed copper complexes against the closes prior art complexes such as metal complexed bacteriochlorins of Pitner and Pucelik. Without a direct comparison showing that the actual performance of the claimed compound is significantly better that what would be predicted from a simple additive effect of Pitner and Pucelik, the showing is insufficient to rebut the obviousness.
Third, the results are not commensurate in scope with the claims. To effectively rebut a rejection of obviousness, the disclosure or evidence of unexpected results must be commensurate in scope with the claims to which the evidence is applied. Broad claim 1 encompasses a wide genus of potential derivatives such as a metallobacteriochlorin, a metallochlorin, and a derivative. However, Applicant’s arguments rely on narrow, specific examples such as CuBC-725, CuBC-775, and CuBC-840 for only about absorption sharpness and absorption maximum, compared against ICG. The limited experimental data does not establish that the entire claimed genus would exhibit the same allegedly unexpected properties (including not only absorption sharpness and maximum but also any other properties).
Further, arguments or conclusory statements in the remarks section of a response do not take the place of evidence in the record. Allegations of unexpected results must be explicitly set forth in the originally filed specification or presented in a formal, signed declaration/affidavit accompanied by actual data. Absent the submission of such proper objective evidence, Applicant’s remarks remain mere unsubstantiated allegations that cannot overcome the rejection.
Accordingly, because the combination of teachings of Pitner and Pucelik would have been obvious to one of ordinary skill in the art, and because the Applicant has not provided sufficient objective evidence to demonstrate unexpected results, the rejection is maintained.
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 1-4, 33, 35, and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. US 12,042,548 in view of Pitner et al. (US 2020 0009272; cited on IDS filed July 5, 2023) and Pucelik et al. (Coordination Chemistry Reviews, 2020; cited on IDS filed February 12, 2026).
This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed March 31, 2026 and those set forth herein.
Regarding new claim 40, claim 1 of the ‘548 recite a compound MB2 having a structure of
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. The compound of MB2 of the ‘548 and the compound (CuBC-2-PEG) of instant claim 40 share the same bacteriochlorin core structure. The MB2 compound contains -COOEt and no PEG moiety, whereas the CuBC-2-PEG contains Cu as a metal, -CooMe, PEF moiety. Claims of the ‘548 do not recite the specific structure of CuBC-2-PEG of instant claim 40.
As discussed above, Pitner discloses a compound of Formula IA
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(¶ 57). The compound of Formula IA and the compound (CuBC-2-PEG) of instant claim 40 share the same bacteriochlorin core structure. The substituent definition in ¶ 59 provides a broad list of permissible groups that cover all the functional groups present in the CuBC-2-PEG of instant claim 40. Specifically, Pitner discloses that R1, R2, and R5 can be H; R3 and R4 can be alkyl; R6 can be hydrophilic groups or linking groups; R7 can be ester; R8 can be H or alkoxy; and the compound can be metalated (¶ 59; ¶ 62). Pitner also discloses a water soluble metallobacteriochlorin such as
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(¶ 20; FIG. 7). Pitner discloses that Cu can be complexed with bacterochlorins (¶ 80) and that the solubilizing (hydrophilic) groups such as PEG chains can improve the biolabeling efficiency and bioconjugate stability (¶ 49). The water soluble metallobacteriochlorin of Pitner and the CuBC-2-PEG of instant claim 40 share the same bacteriochlorin core structure with various functional groups including PEG units. 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 MB2 compound of the ‘548 by including Cu as a complexed metal and PEF moieties as taught by Pitner for preparing a more effective compound with improved characteristics and solubility. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Pucelik teaches a specific metallobacteriochlorin having PEG groups. A person of ordinary skill in the art would have been motivated to utilize Cu as a complexed metal based on the specific requirements of the intended applications as a design choice. The water soluble metallobacteriochlorin of Pitner contains a functionalized phenyl-carboxylic acid tail at the bottom meso-position (R8), whereas the structure of the instant claim 40 has no bottom meso-tail (only H). However, Pitner already teaches that the R 8 can be H (¶ 59), and removing the bottom meso-tail constitutes a predictable and routine optimization in pharmaceutical compound design. Where bioconjugation to an antibody or peptide is not required, deleting this structurally burdensome link is a logical modification with a clear expectation of success to achieve a more streamlined, synthetically accessible, and stable standalone agent. The water soluble metallobacteriochlorin of Pitner has shorter PEG chains with eight repeating units, whereas the structure of the instant claim 40 possesses a longer PEG chain with twelve repeating units. A person of ordinary skill in the art would have been motivated to tune the number of PEG repeating units as a design choice according to the desired requirements of the specific applications. The repeating number of PEG unit is a clearly result-effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the number of the PEG repeating units such as twelve repeating units in order to best achieve the desired solubility profile, as the length of the PEG chain critically determines the hydrophilicity of the compound. Similarly, the length of alky chain is a clearly result-effective parameter that a person of ordinary skill in the art would routinely optimize as a design selection. It would have been customary for an artisan of ordinary skill to determine the length of the alkyl chain such as methyl in order to best achieve the desired solubility profile, as the length of the alkyl chain critically determines the physical properties and specific chemical reactivity of the compound. Compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties (MPEP 2144.09).
Applicant argues that claims of U.S. Patent No. 12,042,548 recite that bacteriochlorin is complexed to nickel, cobalt, or iron but do not disclose the feature that the metallobacteriochlorin, metallochlorin, or derivative thereof is complexed to copper. Applicant argues that neither reference provides a reason why a person of ordinary skill would have modified the compounds of the '548 patent in the particular manner required to arrive at Applicant's claimed copper-complexed photoacoustic imaging contrast agents.
This argument is unpersuasive. As discussed above, Pitner teaches the copper-complexed compound of instant claim 1. As discussed in the Office Action mailed March 31, 2026, a person of ordinary skill in the art would have been motivated to select metal ions such as copper as taught by Pitner to be complexed with bacteriochlorins based on the specific requirements of the intended application. Such routine optimization represents nothing more than the predictable selection of known materials from a finite pool of options to achieved a predictable result. Further, copper, nickel, cobalt, and iron are all neighboring transition metals on the periodic table sharing highly similar coordination geometries. Substituting one transition metal for another within the same well-known macrocycle constitutes an obvious variant.
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 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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