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 .
Election/Restrictions
Applicant originally elected without traverse the compound, Flav7, in the reply filed on 5/13/2024. However, the elected species did not meet the limitations of claim 1. During a telephone conversation with Alexander Chatterley on 6/18/2024 a provisional election was made without traverse to prosecute Compound 8.
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Affirmation of this election was made by applicant in the reply of 11/20/2024. Accordingly, claims 3, 6, 29, 31, 36, 48, 55-56 were withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
In the reply of 4/29/2025, Applicant cancelled claims 1-42, 44-49, 51-60, 62, 64-65, 67-69, and amended claim 43 to recite compounds not drawn to previously elected species, Compound 8. Since the elected species were no longer encompassed by the currently pending claims, in an effort to advance prosecution, the Examiner selected the following species;
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Accordingly, claims 50 and 71-79 were withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a non-elected invention.
In the reply of 9/8/2025, Applicant cancelled claims 1-42, 44-49, 51-60, 62, 64-65, 67-69 and amended claim 43 to recite compounds not drawn to the species elected by the Examiner. Since the elected species is no longer encompassed by the currently pending claims, in an effort to advance prosecution, the Examiner has elected the following species;
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Accordingly, claims 73, 75-79, 81 (new), and 83 (new) are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a non-elected invention. Claim 72 previously withdrawn from consideration as a result of the restriction requirement, is hereby rejoined and fully examined for patentability.
Status of Claims
Cancelled: 1-42, 44-60, 62, 64, 65, 67-71, 74
Withdrawn: 73, 75-79, 81, 83
Examined Herein: 43, 61, 63, 66, 72, 80, 82
Priority
Priority to PRO 62/775,788 filed on 12/5/2018 and PCT/US19/64790 filed on 12/5/2019 is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/11/2021, 10/28/2021, 4/5/2021, 12/30/2022, 5/13/2024, 9/27/2024, 4/29/2025, and 11/3/2025 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 6/4/2021 are accepted.
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 43, 61, 72, 80, and 82 are rejected under 35 U.S.C. 103 as being unpatentable over Telfer (US 5,262,549, Patented 11/6/1993).
With respect to claim 43, 61, 72, 80, and 82, Telfer discloses the following compound, 9-5-(11-[1,1-dimethylethyl]-2,3,6,7-tetrahydro-1H,5H –[1]benzopyrano[6,7,8-ij]quinolizin-9-ylidene]penta-1,3- dienyl)-11-[1,1-dimethylethyl]-2,3,6,7-tetrahydro-1H,5H-[b]benzopyrano[6,7,8-ij]quinolizinium tetrafluoroborate (“Compound 36”): [Telfer, Col. 33, Line 18-34]
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[Structure drawn by Examiner using CAS Draw based on the description of compound 36 disclosed by Telfer. This depiction is provided for clarity only. The basis of the rejection remains solely on the teachings of the cited reference(s)]
Telfer does not explicitly disclose a compound of claim 43.
However, with respect to claim 43, 61, 72, 80, and 83, Telfer discloses that compound 36 is a species of general Formula I:
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[Telfer, Col. 6, Line 1-15]
wherein,
Q is CR6=CR7-CR8=CR9, and
R6, R7, R8, R9, and R10 are independently H. [Telfer, Col. 33, Line 20-24]
(Also, with respect to general formula I: R1 is a substituted alkyl group, R3 together with R2 and R4 comprise two saturated heterocyclic rings containing an element of group 5A (nitrogen) fused to the benzene ring of the associated benzpyrylium nucleus, and R5 is hydrogen [Telfer, Col. 33, Line 20-40])
R5 is a hydrogen atom
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[Structure drawn by Examiner using CAS Draw based on the description of compound 36 disclosed by Telfer. This depiction is provided for clarity only. The basis of the rejection remains solely on the teachings of the cited reference(s)]
Telfer further discloses Q may be a group of CR6=CR7-CR8=CR9-CR10=CR11, wherein R8 and R10 together form a bridging group B, such that the bridging group B and the three carbon atoms of the heptamethine chain lying between the ends of the bridging group form a cyclohexenyl ring. [Telfer, Col. 6, Line 47-59]. Moreover, Telfer discloses each R6 independently is a hydrogen atom or a C1-C6 alkyl group and each R7, R8, R9, R10 and R11 independently is a hydrogen atom, a C1-C6 alkyl group, or a halogen atom. [Telfer, Col. 6, Line 41-45]
Accordingly, Telfer discloses, in one embodiment, Q is CR6=CR7-CR8=CR9-CR10=CR11:
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[Structure drawn by Examiner using CAS Draw based on the description of Q disclosed by Telfer. This depiction is provided for clarity only. The basis of the rejection remains solely on the teachings of the cited reference(s)]
wherein,
R8 and R10 are a bridging group that forms cyclohexenyl,
R6, R7, R8, R10, and R11 is H, and
R9 is halogen. [Telfer, Col. 6, Line 40-58]
Modifying Compound 36 so that Q is a group CR6=CR7-CR8=CR9-CR10=CR11, wherein R8 and R10 together form a bridging group B such that the bridging group B and the three carbon atoms of the heptamethine chain lying between the ends of the bridging group form a cyclohexenyl ring, and wherein R6, R7, R8, R10 and R11 is a hydrogen atom and R9 is a halogen atom (including Cl), results in the compound of 43, 61, 72, 80, and 82:
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[Structure drawn by Examiner using CAS Draw based on the described modification to Q substituent of compound 36 disclosed by Telfer. This depiction is provided for clarity only. The basis of the rejection remains solely on the teachings of the cited reference(s)]
wherein,
X is halogen (including Cl),
Y is O+, and
W is O.
It would be obvious to one of ordinary skill in the art to modify compound 36 disclosed by Telfer so that Q is a group of CR6=CR7-CR8=CR9-CR10=CR11, wherein R8 and R10 together form a bridging group B such that the bridging group B and the three carbon atoms of the heptamethine chain lying between the ends of the bridging group form a cyclohexenyl ring, wherein R6, R7, R8, R10 and R11 is a hydrogen atom and R9 is a halogen atom (including Cl) and have a reasonable expectation of success. Telfer discloses compound 36, wherein Q is CR6=CR7-CR8=CR9, and R6, R7, R8, and R9 are independently H. However, Telfer further discloses compound 36 is a species of general formula I, wherein Q may be a group of CR6=CR7-CR8=CR9-CR10=CR11, R8 and R10 together form a bridging group B, such that the bridging group B and the three carbon atoms of the heptamethine chain lying between the ends of the bridging group form a cyclohexenyl ring, each R6 independently is a hydrogen atom or a C1-C6 alkyl group, and each R7, R8, R9, R10 and R11 independently is a hydrogen atom, a C1-C6 alkyl group, or a halogen atom. Thus, Telfer establishes that compound 36 is species of general formula I, wherein Q is CR6=CR7-CR8=CR9, and general formula I alternatively allows Q to be CR6=CR7-CR8=CR9-CR10=CR11. Therefore, it is reasonable to expect that compound 36 may be modified to embrace this alternative, so that Q is a group of CR6=CR7-CR8=CR9-CR10=CR11, as defined above. One would have been motivated to do so to achieve structural variability by varying the Q substituent while allowing the substituent to maintain its function as a bridging group. [Telfer, Col. 10, Line 41-64]
Claims 43, 61, 63, 66, 72, 80, and 82 are rejected under 35 U.S.C. 103 as being unpatentable over Telfer, as applied to claim 43, 61, 72, 80, and 82 above, and further in view of Nairne (US 2011/0280806 A1, Published 11/17/2011).
With respect to claim 43, Telfer discloses the teachings above.
With respect to claim 61 and 63, Telfer further discloses compound 36 is a dye useful as a visible and infra-red absorber. [Telfer, Col. 8, Line 47-58]
Telfer does not disclose a method of obtaining an image or a method of administering a therapy.
However, with respect to claim 61 and 63, Nairne discloses a method comprising:
administering a near-infra red (NIR) absorbing dye,
illuminating the compound with excitation light, thereby causing the compound to emit fluorescence; and
detecting the fluorescence. [Nairne, 0002, 0124-0125]
Combining the compound disclosed by Telfer with the method disclosed by Nairne, results in the methods of instant claim 63 and 66.
It would be obvious to one of ordinary skill in the art to combine the compound disclosed by Telfer with the method disclosed by Nairne and have a reasonable expectation of success. Telfer discloses compound 36 is a dye useful as a visible and infra-red (IR) absorber. Nairne discloses a method comprising administering a near-infra red (NIR) absorbing dye, illuminating the compound with excitation light, thereby causing the compound to emit fluorescence; and detecting the fluorescence. So, Telfer discloses an IR dye and Nairne discloses a method comprising administering, illuminating, and detecting the fluorescence of an IR dye. Thus, the combined teachings of Telfer and Nairne suggest the IR dye disclosed by Telfer may function as the IR dye in the method disclosed by Nairne. Therefore, it is reasonable to expect the compound disclosed by Telfer may combined with the method disclosed by Nairne. 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. In the instant case, Nairne discloses the aforementioned method enables a subject to be diagnosed based on the fluorescence intensity of the image. [Nairne, 0125] Therefore, one would have been motivated by the expectation that compound 36 could be used in a method that enables a subject to be diagnosed based on the fluorescence intensity of the image.
Response to Arguments
Applicant's arguments filed 3/19/2026 have been fully considered but they are not persuasive.
Applicant asserts “As is apparent based on the above graphical depiction, the embodiments disclosed in Telfer encompass numerous possible options for the bridging group. However, despite all of the countless embodiments, Telfer makes no mention of a halo-substituted cyclohexenyl bridging group. To the contrary, Telfer teaches away from the selection of halo-substituted bridging groups.” [Remarks 3/19/2026, Page 3, Paragraph 2-Page 4, Paragraph 1]
(To the extent that Applicant is implying that the exemplified embodiments disclosed by Telfer do not comprise a halo-substituted bridging group, and therefore teaches away from the selection of halo-substituted bridging groups)
Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. The prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed. Telfer does not criticize, discredit, or otherwise discourage the selection of halo-substituted bridging groups. On the contrary, Telfer discloses halo-substituted bridging groups as species of Q. Moreover, Telfer discloses an exemplary heptamethine dye (1E) comprising a halo-substituted bridging group:
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[Telfer, Figure 5]
Therefore, Telfer does not teach away from the selection of halo-substituted bridging groups.
Applicant asserts “To produce an effective IR-absorbing dye, one of ordinary skill in the art would have been motivated to modify a compound having the longest-wavelength absorbance and highest extinction coefficient, as the aforementioned features would focus the absorbance into the IR spectrum and increase the intensity of the absorbance…. Therefore, one of ordinary skill in the art would have quickly surmised that the halo-substituted bridging group greatly reduces both absorbance and extinction coefficient. Thus, in view of Telfer, one of ordinary skill in the art would not have been motivated to modify compound 36, let alone to include a halo-substituted bridging group.” [Remarks 3/19/2026, Page 5, Paragraph 2-3 and Page 6, Paragraph 1]
The rationale to modify the prior art does not have to be rooted in a desire to improve properties thereof. The rationale to modify the prior art may be expressly stated in the prior art, expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. Moreover, yielding a compound having the longest-wavelength absorbance and highest extinction coefficient is not the only way to produce an effective IR-absorbing dye. A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use. Therefore, a POSITA would not be motivated to produce an effective IR-absorbing dye, in order to modify the compound disclosed by Telfer. This motivation suggested by the Applicant seemingly reflects an advantage or result discovered by applicant. However, it is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant.
Applicant asserts “Critically, Telfer provides no teaching or suggestion that would have allowed one of ordinary skill in the art to predict the effect of the aforementioned modifications to arrive at the claimed compounds from compound 36 would be successful; to the contrary, Telfer counsels against several of the modifications (e.g., the inclusion of the halo-substituted bridging group).” [Remarks 3/19/2026, Page 6, Paragraph 2]
Applicant’s arguments are not persuasive because Applicant improperly equates obviousness with predictability of the effects resulting from a modification. Obviousness does not require absolute predictability. Therefore, a POSITA need not to predict that the effect of the aforementioned modifications would be successful. Rather, a POSITA would need only to have a likelihood of success in modifying the prior art. In the instant case, it is reasonable to expect that the compound disclosed by Telfer could be modified because the modification falls within the scope of general formula I. Accordingly, compound 36, as a species of general formula I, can reasonably be modified within that disclosed framework. Moreover, the “reasonable expectation of success” requirement relates to the likelihood of success of modifying the prior art, not the effects resulting therefrom.
Applicant asserts “Moreover, Telfer provides essentially no guidance for selecting the features of the polymethine chain…. In view of the foregoing, to arrive at the presently claimed compounds from Telfer, one of ordinary skill in the art would have at least needed to:” [Remarks 3/19/2026, Page 6, Paragraph 3]
Applicant’s arguments are not persuasive because a claim is not patentable where the subject matter merely implements a predictable variation of the prior art. The claimed halo-cyclohexenyl bridging group is merely a variation of the Q substituent disclosed by Telfer and falls within the scope of general formula I.
Applicant asserts “In view of the foregoing, it is not reasonable to conclude that one of ordinary skill in the art would have been motivated to arrive at the claimed compounds. To the contrary, it is Applicant's own disclosure, rather than Telfer, that teaches the use of halo-cyclohexenyl bridging groups as effective elements in IR-absorbing polymethine dyes. Thus, in view of the numerous failings of Telfer the Examiner's assertion that one of ordinary skill in the art would have been motivated to arrive at the presently claimed compounds based on Telfer can only be viewed as impermissible hindsight.” [Remarks 3/19/2026, Page 6, Paragraph 1]
Applicant’s argument is not persuasive because Telfer teaches the use of halo-cyclohexenyl bridging groups as species of Q. Thus, Applicant’s claim that the Examiner relied on impermissible hindsight is misplaced because the use of halo-cyclohexenyl bridging groups was gleaned from Telfer, not the Applicant’s disclosure. Moreover “the use of halo-cyclohexenyl bridging groups as effective elements in IR-absorbing polymethine dyes” is not a claimed limitation, nor does it form any basis for supporting the instant rejection.
Applicant asserts “Even if, arguendo, one of ordinary skill in the art were motivated to modify compound 36, there is nothing in Telfer that would have led to a reasonable expectation of success that the modified compounds would function as dyes.” [Remarks 3/19/2026, Page 6, Paragraph 2]
Applicant’s argument is not persuasive because the Telfer disclosure is drawn to bisbenzpyrylium dyes. Telfer discloses general formula I is a bis(benzpyrylium) polymethine dye. Compound 36 is a species of general formula I. Accordingly, a POSITA would expect the modified compound to retain functionality as a dye because it falls within the scope of general formula I.
Applicant asserts “Nairne is drawn to dyes structurally unrelated to the claimed compounds, for example, cyanine dyes, for use in in vivo imaging.” [Remarks 3/19/2026, Page 7, Paragraph 2]
Applicant’s argument is not persuasive because references need not be structurally analogous to be combinable. Moreover, Nairne is drawn to NIR dyes, as is Telfer.
Applicant asserts “Furthermore, Nairne discloses only trimethine dyes, in contrast to the presently claimed compounds, and teaches away from exchanging the trimethine chain…. What is more, Nairne does not disclose any bridging groups, much less the presently claimed halo cyclopentenyl bridging group. Additionally, in contrast with both the dyes disclosed in Telfer and the presently claimed dyes, the dyes disclosed in Nairne are modified with water solubilizing groups.” [Remarks 3/19/2026, Page 7, Paragraph 2]
Applicant’s arguments are not persuasive because the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of the alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed. Accordingly, Nairne does not “teach away” from exchanging the trimethine chain merely because the disclosure is drawn to trimethine dyes. Moreover, Nairne is relied upon for its disclosure of the method and not for any structural features that form the basis of the instant rejection. Thus, Applicant’s criticism of the NIR dyes disclosed by Nairne is immaterial and fails to undermine the basis of the rejection.
Applicant asserts “Telfer does not teach or suggest any application of the disclosed dyes in vivo. Therefore, there is nothing in Telfer that would have motivated one of ordinary skill in the art to combine Telfer and Nairne.” [Remarks 3/19/2026, Page 7, Paragraph 3]
Applicant’s argument is not persuasive because
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). The instant rejection is based on the combined teachings of Telfer and Nairne, not Telfer alone. Moreover, the motivation to combine Telfer and Nairne is reasoned from the teachings of Nairne as cited in the OA of 11/25/2025.
Applicant asserts “Even if, arguendo, one of ordinary skill in the art were motivated to combine Telfer and Nairne, nothing in the combination of references would have produced a reasonable expectation of success in doing so. The combination of references teaches that halo-substituted bridging groups would be deleterious to IR-absorbing dyes, in addition to teaching that polymethine chains longer than trimethine suffer from chemical and photostability issues.” [Remarks 3/19/2026, Page 7, Paragraph 4]
Applicant is asked to cite this teaching from Telfer or Nairne, as the Examiner is unable to locate these teachings in either reference. In the absence thereof, arguments presented by applicant cannot take the place of evidence in the record.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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