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 BC-1 in the reply filed on 6/6/2025 is acknowledged.
PNG
media_image1.png
238
525
media_image1.png
Greyscale
Claim 2, 6-12, 14-16, and 34-36 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to the nonelected compounds of claim 1, there being no allowable generic or linking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
Withdrawn: 2, 6-12, 14-16, 34-36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Withdrawn Rejections
The rejection of claims 1, 3, 4, and 19 under 35 U.S.C. 102(a)(2) over Pitner is hereby withdrawn in view of Applicant’s substantive amendments to claim 1.
The rejection of claims 1, 3, 4, and 18-20 under 35 U.S.C. 103 over Pitner is hereby withdrawn in view of Applicant’s substantive amendments to claim 1.
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, 3-5, 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;
PNG
media_image2.png
292
481
media_image2.png
Greyscale
[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:
PNG
media_image3.png
106
135
media_image3.png
Greyscale
[Page 7755, Scheme 3, B4]
Also, with respect to claim 1, Zhang discloses a bioconjugatable bacteriochlorin, B2;
PNG
media_image4.png
351
683
media_image4.png
Greyscale
[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]
PNG
media_image5.png
239
128
media_image5.png
Greyscale
[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 that m is an integer of 12 or more.
However, with respect to claims 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 B4 compound 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 B2 compound 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.
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 that these compounds may alternatively comprise PEG8 moieties (m = 8). Thus, Zhang demonstrates that the number of PEG units is 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 that are substantially similar to B2 or B4 comprising PEG12 moieties or higher (m ≥ 12) are presumed to possess similar properties as B2 or B4, respectively. Additionally, modifications to homologous compounds are well within the technical grasp of one of ordinary skill in the art. Therefore, it is reasonable to expect that 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. МРЕР 2144(1). In the present 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 functionality 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 that Zhang discloses the B4 compound comprises the bioconjugatable group alkyl-CO2H.
Zhang does not disclose that B4 comprises a bioconjugatable group (G), alkyl-CO2NHS.
However, with respect to claims 1, 17, 30, and 33, Jiang discloses the following hydrophilic tetracarboxy-bacteriochlorin comprising a bioconjugatable group, (CH2)3CO2HNHS.
PNG
media_image6.png
325
265
media_image6.png
Greyscale
[Jiang, Page 405, Chart 3, BC9]
Jiang discloses that the carboxylic acid and NHS esters enable the bacteriochlorin to conjugate to a peptide. Moreover, Jiang discloses that 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 B4 compound 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 B4 compound disclosed by Zhang by adding an NHS ester to form alkyl-CO2NHS and have a reasonable expectation of success. Zhang discloses a bacteriochlorin derivative (”B4”) comprising a bioconjugatable group, alkyl-CO2H. Jiang discloses a bacteriochlorin derivative comprising a bioconjugatable group, alkylCO2NHS. Jiang further discloses that 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 acids, NHS esters are suitable moieties for conjugating 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. MPEР 2144(II). In the present case, Jiang discloses that 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 adding an NHS ester to the bioconjugatable group to form alkyl-CO2NHS, would enable the B4 compound 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's arguments are not persuasive because Applicant's reasoning conflicts with the requirements for demonstrating unexpected results as outlined in MPEP 716.02 (Allegations of Unexpected Results).
Applicant's reasoning is seemingly:
BC-1, having 12 PEG chains, exhibits a superior performance over Zhang's B4, having 4 PEG chains. Namely, the superior performance is an improved maximum stain index. BC-2, having 12 PEG chains, exhibits superior performance over the same compound having 24 PEG chains. Namely, the superior performance is an improved FWHM. Therefore, since BC-1, having 12 PEG chains, is superior to the same compound having 4 PEG chains (less than the claimed range of m ≥ 12) and BC-2, having 12 PEG chains is superior to the same compound having 24 PEG chains (more than the claimed range of m ≥ 12), then these results, taken together, demonstrate that the claimed invention exhibits a superior performance over the prior art. [Remarks 6/8/2026, Page 16, Paragraph; Page 17, Paragraph 3; Page 18-19 (entire)] Specifically, Applicant asserts, "these data provide additional evidence of the trend for bacteriochlorins substituted with longer PEG chains to be superior to those with shorter PEG chains." [Remarks 6/8/2026, Page 15, Paragraph 3]
This reasoning is flawed for the following reasons:
Applicant seemingly believes that BC-1 and BC-2 are sufficient to establish unexpected results of the entire genus of "bacteriochlorins substituted with longer PEG chains." They are not. The claimed invention is not drawn to "bacteriochlorins substituted with longer PEG chains," and this characterization substantially overly generalizes the claimed invention. The claimed invention is drawn to the compound of Formula (II), which comprises a specific scaffold comprising several substituents, each substituent having multiple substitution patterns. PEG chains are just one substituent that may be present in Formula (I). This is one reason why Applicant's results are not commensurate in scope with the claimed invention. 716.02(d). Applicant's data cannot support an assertion of superiority for the entire genus of claim 1, as it is drawn only to a narrow embodiment of the claimed invention.
Furthermore, BC-1 and BC-2 are distinct compounds. Applicant cannot combine the results provided for BC-1 with those for BC-2 to conclude that "bacteriochlorins substituted with longer PEG chains" are superior to those with shorter PEG chains. Because BC-1 and BC-2 differ structurally, it is unclear whether the observed differences in staining or brightness are attributable to PEG chain length or to other differences between the compounds.
Moreover, superiority of a property shared with the prior art is evidence of nonobviousness. Superiority is exhibited by a property (or multiple properties). Therefore, each property that Applicant contends is superior must have evidence in accordance with MPEP 716.02 (Allegations of Unexpected Results).
Consider Applicant's comparison of BC-1 with Zhang's B4. The property that Applicant contends is superior to B4 is maximum stain index. Therefore, Applicant's results comparing BC-1 with B4 must be (1) commensurate in scope with the claimed invention, (2) compared with the closest prior art, (3) in fact unexpected, and (4) of both statistical and practical significance.
Also, consider Applicant's comparison of BC-2 (12 PEG chains) with BC-2 (24 PEG chains). The property that Applicant contends is superior is FWHM. Therefore, Applicant's results comparing BC-2 (12 PEG chains) with BC-2 (24 PEG chains) must be (1) commensurate in scope with the claimed invention, (2) compared with the closest prior art (or equally close art), (3) in fact unexpected, and (4) of both statistical and practical significance.
Applicant may not satisfy the requirement outlined in MPEP 716.02 (Allegations of Unexpected Results), for example, by combining results that BC-1 compared with B4 are (1) commensurate in scope with the claimed invention, (2) compared with the closest prior art, and results that BC-2 (12 PEG chains) compared with BC-2 (24 PEG chains) are (3) in fact unexpected, and (4) of both statistical and practical significance.
This is especially the case, as it relates to the requirement that the results must be (1) commensurate in scope with the claimed invention. To demonstrate the criticality of the PEG chain (m) comprising 12 units or more, Applicant should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range, such that the Office can ascertain a trend in the data provided MPEP 716.02(d)(II) & MPEP 2145. Two data points do not constitute a trend. Generally, at least three data points are sufficient to constitute a trend: one below the claimed range, one above the claimed range and (3) and one within the claimed range. Accordingly, as explained above, Applicant may not combine the two data points from the comparison of BC-2 (12 PEG chains) with BC-2 (24 PEG chains) with the two data points from the comparison of BC-1 with B4 to produce 4 data points.
Furthermore, with respect to Applicant's comparison of BC-2 (12 PEG chains) with BC-2 (24 PEG chains):
The alleged unexpected results must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. MPEP 716.02(e). Comparing BC-2 (12 PEG chains) with BC-2 (24 PEG chains) does not constitute comparing the claimed subject matter with the closest prior art because both BC-2 (12 PEG chains) and BC-2 (24 PEG chains) fall within the scope of the claimed invention, as they are both species of Formula (II). Neither BC-2 (12 PEG chains) nor BC-2 (24 PEG chains) have been cited as prior art. Applicant's results merely establish that one embodiment of the claimed invention is superior to another embodiment of the claimed invention.
Applicant's assertions with respect to Bieniarz, even if meritorious, fail to establish the allegations of unexpected results in view of the deficiencies identified above. [Remarks 6/8/2026, Page 16, Paragraph 2-3; Page 17, Paragraph 1-21] PEG groups are necessarily water solubilizing groups independent of whether Bieniarz defines them as such.
In summary, Applicant's comparison of BC-1 with B4 is not commensurate in scope with the claimed invention because it is only drawn to a narrow embodiment of the claimed invention and only comprises two data points, which do not constitute a trend. Additionally, Applicant's comparison of BC-2 (12 PEG chains) with BC-2 (24 PEG chains) is not commensurate in scope with the claimed invention because it is only drawn to a narrow embodiment of the claimed invention, and only comprises two data points, which do not constitute a trend, and does not compare the claimed subject matter with the closest prior art.
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
