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 .
Acknowledgments and Claim Status
The Examiner acknowledges receipt of the amendment filed 5/28/2026 wherein the specification and claims 1-4 were amended.
Note(s): Claims 1-26 are pending.
Priority
This application is a 371 of PCT/US21/46181 filed 8/16/2021 and PCT/US21/46181 claims benefit to provisional application 63/066,072 filed 8/14/2020.
Note(s): The earliest effective filing date is 8/14/2020 as the pending invention is fully supported in the provisional application.
Claim Interpretation
Independent claim 1 is directed to compounds of formula
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wherein R, R2, R3, R4, R5, R6, R7, R8, and R9 are defined therein. It should be noted that the definitions of R, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12 include alkyl groups. According to Applicant’s definition of
‘alkyl’ on page 7, paragraph [0036], of the specification, the term includes both substituted and unsubstituted groups; however, independent claim 1 was amended on 5/28/2026 to specifically state that the C1-C4 alkyl groups are unsubstituted.
Claim 8 is directed to determining the presence and/or location of a solid tumor as set forth therein.
Claim 15 is directed to a method of imaging a solid tumor as set forth therein.
Claim 21 is directed to a method of determining margins of a soldi tumor as set forth therein.
Claim 26 is directed to a kit comprising
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.
Response to Applicant’s Amendment and/or Arguments
The Applicant's arguments and/or amendment filed 5/28/2026 to the rejection of claims 1-26 made by the Examiner under 35 USC 102, 103, and/or 112 have been fully considered and deemed persuasive-in-part for the reasons set forth below.
112 Second Paragraph Rejections
The outstanding 112 second paragraph rejections are WITHDRAWN because Applicant amended the claims to overcome the rejections.
102 Rejection
The outstanding 102 rejection is withdrawn because Applicant amended the claims to specifically state that R, R1, R2, and R3 are unsubstituted C1-C4 alkyl groups.
103 Rejection
Note(s): The 103 rejection below was modified to reflect the amendment to independent claim 1 filed 5/28/2026.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
I. Claims 1-25 are rejected under 35 U.S.C. 103 as being unpatentable over Tung et al (US 20170072072).
Independent claim 1 is directed to compounds of formula
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wherein R, R2, R3, R4, R5, R6, R7, R8, and R9 are defined therein. Claims 2-4 are directed to structures having various alkyl groups and/or hydrogen substituents present at positions R, R2, R3, R4, R5, R6, R7, R8, and/or R9.
Tung et al disclose various compounds encompassed by pending claim 1. In particular, the following structures are disclosed:
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(Figure 5A; page 8, left column first structure; page 17, claim 20) wherein R and R1 = methyl; R8 and R9 = hydrogen; Z = oxygen; Y = CR11R12 wherein R11 and R12 = hydrogen; R2 and R3 = substituted alkyl groups;
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(Figure 6 and page 7, paragraph [0078]; page 17, claim 20) wherein R and R1 = one is methyl and the other a substituted alkyl groups; R8 and R9 = hydrogen; Z = oxygen; Y = CR11R12 wherein R11 and R12 = hydrogen; R2 and R3 = methyl; and
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(page 8, left column, second structure; page 17, claim 20) wherein R and R1 = one is methyl and the other a substituted alkyl groups; R8 and R9 = hydrogen; Z = oxygen; Y = CR11R12 wherein R11 and R12 = hydrogen; R2 and R3 = substituted alkyl group.
While the document specifically discloses substituted alkyl groups at various locations on the structure, it would have been obvious to one of ordinary skill in the art before the effective date of the pending invention to include unsubstituted alkyl groups as well for the following reasons. Specifically, on pages 2-3, paragraph [0026] of Tung et al, it is disclosed that the alkyl group may be substituted or unsubstituted. Thus, it is not required that the document disclose specific species that include both substituted and unsubstituted groups. The structures disclosed supra illustrated at those located that Applicant reference as having alkyl groups contain alkyl groups as well even though they are substituted. Also note that at those specific locations containing substituted alkyl groups (Applicant’s R2, R3, R, and R1 positions which correspond to Tung et al’s variables R1, R2, R5, and R6 (see page 7, Formula IV), respectively) are define as “alkyl” (see page 5, paragraphs [0058] and [0061]).
Since Tung et al (the cited prior art) has defined the term “alkyl” to include both substituted as well as unsubstituted alkyl groups, it would have been obvious to a skilled artisan prior to the effective date of the pending invention to replace the substituted alkyl groups therein with unsubstituted alkyl groups.
Hence, the skilled artisan would expect structures having Formula IV,
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, to have both substituted and non-substituted alkyl groups present in the structure. The locations wherein non-substituted alkyl groups may be present are consistent with Applicant’s R, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12.
For the reasons set forth supra, the limitations of claims 1-4 are rendered obvious.
Claim 5 is directed to a compound of claim 1 in combination with a pharmaceutically acceptable carrier.
Tung et al disclose that one may generate pharmaceutical formulations comprising one or mor pharmaceutically acceptable carriers and optionally one or more other therapeutic ingredients (page 8, paragraph [0081]). Thus, the limitation of claim 5 is met.
Claim 6 is directed to the concentration of the compound being 0.5 µM to 10 µM.
Tung et al disclose CypH-1 (see (Figure 2A; page 7, paragraph [0078]) which is listed in independent claim 1 and in a proviso of thereof. While the structure is present in the proviso, it is withing the structure requirements of that of pending independent claim 1 and exemplified in Tung et al. In Tung et al, it is disclosed that the compound is present in and amount of 0.5 µM. Thus, the limitation of claim 6 is rendered obvious.
Claim 7 is directed to a composition that is sprayable or an oral rinse.
Tung et al disclose that the compound/composition may be administered orally or as spray topically ( page 8, paragraph [0082]; page 10, paragraph [0089]; pages 10-11, paragraph [0093]). Thus, the limitation of claim 7 is met.
Claim 8 is directed to a method of determining the presence and/or location of a solid tumor as set forth therein. Claim 9 is directed to generating a signal in less than 5 minutes. Claim 10 is directed to signal detection in less than 1 minute.
Tung et al disclose the compounds/compositions may be used to detect cancer/tumors (page 10, paragraph [0089], [0091], and [0092]). In addition, Tung et al disclose that the cells may be imaging immediately since there is no fluorescence in neutral pH, so after incubation, the cells could be imaging immediately without any washes (page 12, paragraph [0102]). Thus, the limitations of claims 8-10 are met.
Claim 11 is directed to applying the compound topically. Claim 12 is directed to the composition being a spray or oral rinse.
Tung et al disclose that the compound/composition may be administered orally or as spray topically ( page 8, paragraph [0082]; page 10, paragraph [0089]; pages 10-11, paragraph [0093]). Thus, the limitations of claims 11 and 12 are met.
Claim 13 is directed to various tumors selected from ovarian, skin, pancreatic, genitourinary, colon, bladder, brain, esophagus, cervical, oral, and combinations thereof.
Tung et al disclose that various cancers including bladder, brain, colorectal, cervical, genitourinary, ovarian, esophagus, and pancreatic may be evaluated using their compound/composition (page 10,paragraphs [0088], [0091], and [0092]). Thus, the limitations of claim 13 are met.
Claim 14 is directed to solid tumor results in the protonation of the compound.
Tung et al disclose that when the amines of the compound are protonated under acidic conditions, one is able to get results regarding the tumor (pages 11-12, paragraph [0099]). Thus, the limitation of claim 14 is met.
Claim 15 is directed to a method of imaging a solid tumor as set forth therein. Claim 16 is directed to generating a signal in less than 5 minutes. Claim 17 is directed to the signal being directed in less than a minute.
Tung et al disclose the compounds/compositions may be used to detect cancer/tumors (page 10, paragraph [0089], [0091], and [0092]). In addition, Tung et al disclose that the cells may be imaging immediately since there is no fluorescence in neutral pH, so after incubation, the cells could be imaging immediately without any washes (page 12, paragraph [0102]). Thus, the limitations of claims 15-17 are met.
Claim 18 is directed to administering the compound topically. Claim 19 is directed to the compound be used as a spray or an oral rinse.
Tung et al disclose that the compound/composition may be administered orally or as spray topically ( page 8, paragraph [0082]; page 10, paragraph [0089]; pages 10-11, paragraph [0093]). Thus, the limitations of claims 18 and 19 are met.
Claim 20 is directed to various tumors selected from ovarian, skin, pancreatic, genitourinary, colon, bladder, brain, esophagus, cervical, oral, and combinations thereof.
Tung et al disclose that various cancers including bladder, brain, colorectal, cervical, genitourinary, ovarian, esophagus, and pancreatic may be evaluated using their compound/composition (page 10,paragraphs [0088], [0091], and [0092]). Thus, the limitations of claim 20 are met.
Claim 21 is directed to a method of determining tumor margins of a solid tumor as set forth therein.
Tung et al disclose that their compound/composition may be used to detect cancer/tumor before a tumor resection procedure or during the procedure by a topical spray. Thus, it would be obvious to the skilled artisan that tumors may be detect prior to or during a procedure (page 10, paragraphs [0089] and [0091]). On pages 10-11 (paragraph [0093]), it is disclosed that during surgery tumors/cancers that are to be resected, the compound/composition may result in robust fluorescence signal of discrete neoplastic lesion with millimeter range resolution. The fluorescence signal is strikingly enhanced at peripheral regions according to Tung et al. Thus, the limitation of claim 21 is met.
Claim 22 is directed to the compound being used as a spray or an oral rinse.
Tung et al disclose that the compound/composition may be administered orally or as spray topically ( page 8, paragraph [0082]; page 10, paragraph [0089]; pages 10-11, paragraph [0093]). Thus, the limitations of claim 22 are met.
Claim 23 is directed to a signal being detected in less than 5 minutes. Claim 24 is directed to a signal being detected in less than 1 minute.
Tung et al disclose the compounds/compositions may be used to detect cancer/tumors (page 10, paragraph [0089], [0091], and [0092]). In addition, Tung et al disclose that the cells may be imaging immediately since there is no fluorescence in neutral pH, so after incubation, the cells could be imaging immediately without any washes (page 12, paragraph [0102]). Thus, the limitations of claims 23 and 24 are met.
Claim 25 is directed to solid tumors selected from ovarian, skin, pancreatic, genitourinary, colon, bladder, brain, esophagus, cervical, oral, and combinations thereof.
Tung et al disclose that various cancers including bladder, brain, colorectal, cervical, genitourinary, ovarian, esophagus, and pancreatic may be evaluated using their compound/composition (page 10,paragraphs [0088], [0091], and [0092]). Thus, the limitations of claim 25 are met.
For the reasons set forth supra, Tung et al renders obvious the pending invention (claims 1-25).
APPLICANT’S ASSERTIONS
In summary, it is asserted that the rejection should be withdrawn because amended independent claim 1 was amend to disclose that R, R1, R2, and R3 are ‘unsubstituted C1-C4 alkyl groups’ and Tung et al (cited prior art) discloses species with substituted alkyl groups at those locations.
EXAMINER’S RESPONSE
All of Applicant’s arguments were considered, but deemed non-persuasive for reasons set forth supra and those below. (1) Specifically, since there is a 103 rejection, it is not required that Applicant discloses specific species contain unsubstituted alkyl groups in the various location. (2) On pages 2-3, paragraph [0026], Tung et al specifically discloses that the term ‘alkyl’ throughout their disclosure includes both substituted and unsubstituted alkyl groups. (3) The specific species disclosed in Tung et al are structurally similar to those of Applicant’s invention with the exception that they contain substituted alkyl groups. However, it would have been obvious to the skilled artisan prior to the effectively filing date of the pending invention to replace those substituted alkyl groups with non-substituted alkyls as disclosed in the disclosure (pages 2-3, paragraph [0026]). Hence, the rejection is still deemed proper.
II. Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Tung et al (US 20170072072) in view of Mao et al (US Patent No. 8,709,830).
Claims 1-25 are rendered obvious by Tung et al as set forth in detail supra.
Claim 26 is directed to a kit comprising the compound of claim 1.
Mao et al is made of record to illustrate that it is well known in the art to generate kits containing substances that enable one to detail the presences of conditions such as cancer/tumors using a dye (see entire document, especially, abstract; column 1, lines 45-67). Thus, one of ordinary skill in the art would be motivated to generate a kit for diagnostic purposes because of the ever present need for such kits in hospitals, clinics, or other medical facilities. Thus, a skilled practitioner in the art would be motivated to place the compound and/or components such as a pharmaceutically acceptable carrier in various containers to be used at a desired time with the subject. Hence, the limitation of claim 26 is rendered obvious according to the prior art.
APPLICANT’S ASSERTIONS
In summary, the same assertions are made over the claims as set forth in the 103 response above.
EXAMINER’S RESPONSE
All of Applicant’s amendments were considered. The rejection was deemed proper for reasons of record in the Tung et al and Mao et al documents cited supra (see detailed discussion above).
Conclusion
Claims 1-26 are rejected.
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.
Future Correspondences
Any inquiry concerning this communication or earlier communications from the examiner should be directed to D L Jones whose telephone number is (571)272-0617. The examiner can normally be reached M-F.
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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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/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
August 6, 2026
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