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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 2/4/2026 has been entered.
Election/Restrictions
Applicant’s election without traverse of BC-1 in the reply filed on 6/6/2025 is acknowledged.
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Claim 2, 6-12, 14-16, and 34-36 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to the nonelected compounds of claim 1, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/6/2025.
Status of Claims
Cancelled: 13, 21-29
New: 31-36
Withdrawn: 2, 6-12, 14-16, 34-36
Examined Herein: 1, 3-5, 17-20, 30-33
Priority
Acknowledgment is made of applicant's claim for priority under based upon an application filed in PRO 62/850,446 on 5/20/2019 and PCT/US2020/033627 on 5/19/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/15/2022 and 2/2/2026 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 received on 11/19/2021 are accepted.
Withdrawn Rejections
The objection of claim 1 is hereby withdrawn in view of Applicant’s remarks which state “-H” is listed twice intentionally. [Remarks 2/4/2025, Page 12, Paragraph 4]
The rejection of claim 30 under 35 U.S.C. 103 over Jiang, in view of Zhang is hereby withdrawn because, upon further search and consideration, additional art has ben identified that more clearly establishes the prima facie case of obviousness of record.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3, 4, and 19 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Pitner (US 2020/0009272 A1, Filed 2/2/2018).
The applied reference has a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
With respect to claim 1, Pitner discloses a compound of Formula (II):
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[Pitner, Figure 8, MB3 and 0021]
Wherein,
M is a metal
R2 is a solubilizing group -alkynyl-aryl-(Rs)w
Wherein,
W is 0
Or R2 is a linker group -L1-(X1-L2)p-G
Wherein,
L1 is alkynylene
P is 0
G is a bioconjugatable group
R3 is ester
R5 is alkoxy
R10 is H
R12 is a solubilizing group -alkynyl-aryl-(Rs)w
Wherein,
W is 0
R13 is ester
R15 is H, thus meeting the limitations of claim 1. [Pitner, Figure 8, MB3 and 0021]
With respect to claim 3, Pitner discloses R5 is alkoxy, R10 is H, and R15 is H, thus meeting the limitations of claim 3. [Pitner, Figure 8, MB3 and 0021]
With respect to claim 4, Pitner discloses R3 and R13 are each ester, thus meeting the limitations of claim 4. [Pitner, Figure 8, MB3 and 0021]
With respect to claim 19, Pitner discloses a pharmaceutical composition comprising MB3 and a pharmaceutically acceptable carrier, thus meeting the limitations of claim 19. [Pitner, 0013]
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, 3, 4, and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Pitner as applied to claim 1, 3, 4, and 19 above.
With respect to claim 1, Pitner discloses the teachings above.
With respect to claim 18, Pitner discloses a composition comprising:
A compound (MB3) of Formula (II), wherein R2 is a linking group.
Pitner does not explicitly disclose the compound of Formula (II) forms a covalent conjugate with (b).
However, Pitner discloses the compound may further comprise a peptide that binds to a tumor-associated antigen. [Pitner, 0008]
With respect to claim 20, Pitner discloses a method of detecting a target, wherein said target is a compound, cell or particle, wherein the method comprises labelling the target with a conjugate comprising (a) a compound of Formula (II), wherein R2 is a linking group and (b) a peptide. [Pitner, 0008-0010]
Modifying the compound (MB3) disclosed by Pitner by conjugating a peptide to the compound, results in the composition of claim 18 and method of claim 20.
It would be obvious to one of ordinary skill in the art to modify the compound (MB3) disclosed by Pitner by conjugating a peptide to the compound and have a reasonable expectation of success. Pitner discloses a compound (MB3) of Formula (II) comprising a linking group (R2). Additionally, Pitner discloses said compound may further comprise a peptide. In view of this express teaching by Pitner, it is reasonable to expect the compound may be modified by conjugating a peptide to the compound. One would have been motivated to do so because it is prima facie obvious to modify a reference when the rationale for doing so is expressly stated in the prior art. In the instant case, Pitner discloses the compound (MB3) functions as a contrast agent that may be employed in photoacoustic imaging. Pitner further discloses conjugating a peptide to the compound enables the compound to bind to a ligand, a target present on a tumor cell or a cancer cell, or a vascular endothelial cell, or a tumor-associated antigen. [Pitner, 0008-0010] Therefore, one would have been motivated by the expectation that the aforementioned modification could enable the contrast agent disclosed by Pitner to generate a photoacoustic image of a target site comprising a tumor cell or a cancer cell, or a vascular endothelial cell, or a tumor-associated antigen.
Claims 1, 3-5, 18-20, 31, and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Bioconjugatable, PEGylated hydroporphyrins for photochemistry and photomedicine. Narrow-band, near-infrared-emitting bacteriochlorins, 7/22/2016, New Journal of Chemistry, 40:7750-7767).
With respect to claim 1, Zhang discloses a bioconjugatable bacteriochlorin, B4;
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[Page 7755, Scheme 3, B4]
Wherein,
M is -H, -H
R2 and R12 are independently a solubilizing group, aryl-(Rs)w
wherein,
w is 1
Rs is -X2-(L3)z-R17
wherein,
Z is 0,
X2 is -CH2NHC(=O)
R17 is –(C2H4O)m-R18
wherein
m is 4
R18 is methyl
R3 is an ester
R5 is alkoxy
R10 is H
R3 is ester
R15 is -L1-(X1-L2)p-G
wherein,
P is 0,
L1 is an alkynylene
G is a bioconjugatable group.
With respect to claim 3, Zhang discloses R5 is alkoxy, R10 is H, and R15 is -L1-(X1-L2)p-G. [Page 7755, Scheme 3, B4]
With respect to claim 4, Zhang discloses R3 and R13 are each ester. [Page 7755, Scheme 3, B4]
With respect to claim 5, Zhang discloses R2 is:
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[Page 7755, Scheme 3, B4]
Also, with respect to claim 1, Zhang discloses a bioconjugatable bacteriochlorin, B2;
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[Page 7755, Scheme 3, B2]
Wherein,
M is -H, -H
R2 is H
R3 and R13 are independently a solubilizing group, aryl-(Rs)w
wherein,
w is 1
Rs is -X2-(L3)z-R17
wherein,
Z is 0,
X2 is -CH2NHC(=O)
R17 is –(C2H4O)m-R18
wherein
m is 4
R18 is methyl
R5 is alkoxy
R10 is H
R12 is H
R15 is -L1-(X1-L2)p-G
wherein
P is 0
L1 is an alkylene
G is a bioconjugatable group.
With respect to claim 3, Zhang discloses R5 is alkoxy, R10 is H, and R15 is -L1-(X1-L2)p-G. [Page 7755, Scheme 3, B2]
With respect to claim 18, Zhang discloses a composition, B2-Ab, comprising a covalent conjugate formed between:
(a) a compound (B2) comprising a linking group; and
(b) an antibody. [Page 7766, Col. 1, Page 3]
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[Page 7752, Chart 3, B2]
With respect to claim 19, Zhang discloses a pharmaceutical composition comprising B2-Ab and a pharmaceutically acceptable carrier, PBS. [Page 7766, Col. 1, Paragraph 4]
With respect to claim 20, Zhang discloses a method of detecting a target, wherein said target is a particle, wherein the method comprises labelling the particle with B2-Ab. [Page 7760, Col. 2, Paragraph 1 and Figure 4]
Zhang does not disclose m is an integer of 12 or more.
However, with respect to claim 1, 18, 31, and 32, compounds which are homologs (differing regularly by the successive addition of the same chemical group) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. MPEP 2144.09
Modifying the compound, B4, disclosed by Zhang by increasing m from 4 to greater than or equal to 12 results in the compound of claim 1 and 31.
Modifying the compound, B2, disclosed by Zhang by increasing m from 4 to greater than or equal to 12 results in the compound of claim 1, 31, and 32 and the composition of claim 18.
Moreover, one would have been motivated to select B2 and B4 as lead compounds because Zhang demonstrates these compounds are amenable to PEG modification, thereby indicating them as suitable starting points for further structural variation.
It would be obvious to one of ordinary skill in the art to modify the compounds (B2 and B4) disclosed by Zhang by increasing m from 4 to greater than or equal to 12 and have a reasonable expectation of success. Zhang discloses two compounds, B4 and B2, both independently comprising PEG4 moieties (m = 4). Zhang further discloses the compounds may alternatively comprise PEG8 moieties (m = 8). Thus, Zhang demonstrates that the number of units of the PEG moieties are amenable to variation. Moreover, homologous compounds are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. Accordingly, compounds substantially similar to B2 or B4 comprising PEG12 moieties or higher (m ≥ 12), are presumed to possess similar properties as B2 or B4 disclosed by Zhang and modifications to homologous compounds are well within the technical grasp of one of ordinary skill in the art. Therefore, it is reasonable to expect the compounds disclosed by Zhang may be modified by increasing m from 4 to greater than or equal to 12. One would have been motivated to do so because it is prima facie obvious to modify a reference when the rationale for doing so is reasoned from knowledge generally available to one of ordinary skill in the art or established scientific principles. MPEP 2144(I) In the instant case, it is generally known by one of ordinary skill in the art and accepted as an established scientific principle that homologous compounds are presumed to possess similar properties. Therefore, one would have been motivated to achieve structural variability within the class of homologous compounds, without materially affecting the core functionally of the compounds disclosed by Zhang.
Claims 1, 3-5, 17-20, and 30-33 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang, as applied to claim 1, 3-5, 18-20, 31, and 32 above, and further in view of Jiang (Polarity-tunable and wavelength-tunable bacteriochlorins bearing a single carboxylic acid or NHS ester. Use in a protein bioconjugation model system, 10/31/2014, New Journal of Chemistry, 39:403-419).
With respect to claim 1, Zhang discloses the teachings above.
Recall, Zhang discloses the compound B4, wherein the bioconjugatable group is alkyl-CO2H.
Zhang does not disclose the bioconjugatable group (G) of B2 is alkyl-CO2NHS.
However, with respect to claim 1, 17, 30, and 33, Jiang discloses the following hydrophilic tetracarboxy-bacteriochlorin comprising a bioconjugatable group, (CH2)3CO2HNHS.
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[Jiang, Page 405, Chart 3, BC9]
Jiang discloses the carboxylic acid and NHS esters enable the bacteriochlorin to conjugate to a peptide. Moreover, Jiang discloses carboxylic acid and NHS esters are both conjugatable with amines but NHS esters are additionally conjugatable with thiols (i.e. cysteines). [Jiang, Page 404, Col. 2, Paragraph 2]
Modifying the bioconjugatable group of the compound (B4) disclosed by Zhang by adding an NHS ester to form alkyl-CO2NHS, results in the compound of claim 1, 17, 30, and 33.
It would be obvious to one of ordinary skill in the art to modify the bioconjugatable group of the compound (B4) disclosed by Zhang by adding an NHS ester to form alkyl-CO2NHS and have a reasonable expectation of success. Zhang discloses a bacteriochlorin derivative comprising a bioconjugatable group, alkyl-CO2H. Jiang discloses a bacteriochlorin derivative comprising a bioconjugatable group, alkyl-CO2NHS. Jiang further discloses carboxylic acids and NHS esters are both conjugatable with amines but NHS esters are additionally conjugatable with thiols (i.e. cysteines). Thus, Jiang establishes that in addition to carboxylic acid, NHS esters are suitable moieties for conjugation of bacteriochlorins. Accordingly, the combined teachings of Zhang and Jiang suggest that an NHS ester may be added to the bioconjugatable group of the bacteriochlorin derivative disclosed by Zhang. Therefore, it is reasonable to expect the bioconjugatable group of the compound disclosed by Zhang may be modified by adding an NHS ester to form alkyl-CO2NHS. 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 instant case, Jiang discloses CO2NHS esters enable conjugation with thiols (i.e. cysteines) and amides. [Jiang, Page 404, Col. 2, Paragraph 2] Therefore, one would have been motivated by the expectation that the aforementioned modification could enable the compound (B4) disclosed by Zhang to accommodate conjugation with cysteines.
Response to Arguments
Applicant's arguments filed 2/4/2026 have been fully considered but they are not persuasive.
Applicant asserts “Applicant respectfully submits that the Office has not identified any such teaching suggestion or motivation to modify Zhang at all, much less with the specific modification needed to produce a compound according to present Claim 1.” [Remarks 2/4/2026, Page 13, Paragraph 3]
Applicant’s arguments are not persuasive because the Office has provided a reason to modify Zhang based on the expectation that structurally similar compounds will exhibit similar properties. This expectation advantageously enables one of ordinary skill in the art to vary the structure of the compound while retaining its core functionality. Moreover, this rationale is sufficient to establish a prima facie case of obviousness because the rationale to modify the prior art may be reasoned from knowledge generally available to one of ordinary skill in the art or established scientific principles. MPEP 2144(I). Applicant has not meaningfully addressed why the Office’s reliance on this rationale is insufficient to establish a prima facie case of obviousness. In the absence of a substantive rebuttal, Applicant’s remarks fail to overcome the rejection record.
Applicant asserts “However, as the Federal Circuit has made clear allegations of structural similarity alone are insufficient to support a finding of obviousness of a chemical modification.” [Remarks 2/4/2026, Page 13, Paragraph 4]
Applicant’s argument is not persuasive because the cited Federal Circuit decision does not provide a basis to overcome the instant rejection. The instant rejection is consistent with the principles set forth in the MPEP, which states “A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. MPEP 2144.08
Applicant asserts “Specifically, Jiang does not cure, nor does the Office suggest that it cures, Zhang's failure to provide the requisite motivation to select compound B4 as a lead compound and to specifically modify it to produce a compound of present Claim 1.” [Remarks 2/4/2026, Page 15, Paragraph 4-5 and Page 16, Paragraph 1]
The reason to select compound B4 as a lead compound and modify it in the manner asserted in the OA of 11/7/2025 is implicitly provided by the reasonable expectation of success, which establishes that the compound disclosed by Zhang and Jiang both belong to a class of bioconjugatable bacteriochlorins that is amenable to modification. However, for clarity of record, the instant rejection has been updated so that this reasoning is explicit.
Applicant asserts “Thus, these results show a significant enhancement in performance for the compound BC-1, which is a PEG 12 pegylated bacteriochlorin as recited in the present claims, as compared to the PEG4 pegylated bacteriochlorin described by Zhang. Applicant respectfully submits that the superior performance of PEG 12 pegylated bacteriochlorins such as BC-1 over PEG4 pegylated bacteriochlorin would be surprising one of ordinary skill in the art and that therefore the claimed compounds cannot be obvious.” [Remarks 2/4/2026, Page 14, Paragraph 3 and Page 15, Paragraph 1]
Applicant’s statement that the only difference between the BC-1 and PEG4 peglyated bacteriochlorin is the degree of pegylation is acknowledged. However, it is still unclear whether Applicant is asserting that the PEG4 peglyated bacteriochlorin is the exact same as the B4 compound disclosed by Zhang or is an equally close compound. Accordingly, Applicant is asked to provide further clarification.
Still, Applicant’s arguments are not persuasive because the data does not establish that the results are actually unexpected. MPEP 716.02 states “Any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected.”
Bieniarz (US 2017/0089911 A1, Published 3/30/2017) discloses that the addition of a PEG moiety can improve staining intensity. Bieniarz compared the staining intensity of fluorescent dye derivatives comprising no PEG moieties, a PEG4 moiety, and a PEG8 moiety and found that the PEG8 moiety increased staining intensity relative to the PEG4 moiety and the moiety with no PEG. [0281, 0282, Figure 6 and Figure 7]
Additionally, Bieniarz (US 2006/0246523 A1, Published 11/2/2006) compared the staining intensity of signal generating conjugates bearing a PEG4, PEG8, or PEG12 moiety. The results demonstrated that the PEG12 moiety had the darkest overall staining followed by the PEG8 and then PEG4. [01955, Figure 19]
Thus, it is already known in the art that increasing the PEG chain length generally enhances staining properties. Accordingly, it would have been expected that a PEG12 pegylated bacteriochlorin would exhibit a higher maximum stain index compared to a PEG4 pegylated bacteriochlorin. Therefore, the data reported by the Applicant do not demonstrate results that are unexpected.
Applicant asserts “With reference to Table 1,…overall brightness (c x QY) improved by over 40% when moving from the PEG 12 x 2 to the PEG24 x 2 design. The full width at half maximum (FWHM) was also improved with the longer PEG chains. Thus, not only are PEG 12 pegylated bacteriochlorins superior to PEG4 pegylated bacteriochlorins, but PEG24 bacteriochlorins provide additional improvements over PEG 12 bacteriochlorins.” [Remarks 2/4/2026, Page 18, Paragraph 1]
Applicant’s arguments are not persuasive at least because Applicant fails to compare the claimed subject matter with the closest prior art. Applicant compares one embodiment of the claimed invention (BC2 with PEG12) with another embodiment of the claimed invention (BC2 with PEG24). Accordingly, the results do not demonstrate the claimed invention exhibits unexpected results because Applicant has not measured the brightness or FWHM of the compound disclosed by Zhang, which is necessary to establish that the claimed invention exhibits an unexpected brightness or FWHM, while the compound disclosed by Zhang does.
Moreover, Applicant contends the results provided on Page 15 and Page 17, taken together, demonstrate that “not only are PEG 12 pegylated bacteriochlorins superior to PEG4 pegylated bacteriochlorins, but PEG24 bacteriochlorins provide additional improvements over PEG 12 bacteriochlorins.“ However, the results provided on Page 15 are drawn to BC-1 and the results provided on Page 17 are drawn to BC-2. BC-1 and BC-2 are distinct compounds. Therefore, the results cannot be combined to arrive at the above contention, because it is no longer clear whether the observed differences in staining or brightness are contributable to the difference in PEG chain lengths or the other differences that exist between the compounds.
With respect to the overall allegation of unexpected results:
MPEP 716.02(d) states that unexpected results must be commensurate in scope with the claimed invention. Claim 1 of the instant application is drawn to a broad genus encompassing numerous compounds but the data provided by the Applicant is limited to two embodiments thereof, BC1 and BC2. Therefore, the unexpected results contended by the Applicant are not commensurate with at least claim 1. Still, the non-obviousness of a broader claimed range can be supported by evidence based on unexpected results from testing a narrower range if one of ordinary skill in the art would be able to determine a trend in the exemplified data which would allow the artisan to reasonably extend the probative value thereof. To establish unexpected results over a claimed range, Applicant should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range.
However, there is no trend in the data that would allow an artisan to reasonably extend the probative value thereof. Applicant's results are limited to a comparison between a PEG4 and PEG12 chain (with respect to maximum stain index), and a PEG12 and PEG24 chain (with respect to brightness), rather than a broader claimed range (i.e., a PEG4, PEG12, and PEG24 chain with respect to maximum stain index and/or brightness). As a result, there is no trend that can be ascertained from the data due to the structural differences between BC1 and BC2. These structural differences extend beyond the difference in PEG chain length and affect the ability to compare the compounds and draw conclusions across the claimed genus. To demonstrate unexpected results, Applicant should compare a sufficient number of compounds with PEG chains below and beyond BC1 or BC2, rather than comparing compounds with PEG chains below BC1 and above BC2.
/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618