DETAILED ACTION
This Office action details a first action on the merits for the above referenced application No. Claims 1-15 are pending in this application.
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 .
Priority
This application is a 35 USC 111(a) filing that claims benefit as a continuation of international application No. PCT/JP2022/032641 filed on 30 Aug. 2022, and claims benefit under 35 USC 119(a)-(d) to foreign application Nos. JP 2021-141999 and JP 2022-100573 filed on 31 Aug. 2021 and 22 Jun. 2022, respectively.
Claim Objections
Claims 1-5, and 9-10 are objected to because of the following informalities:
in claims 1-5, and 9-10 each instance of “represent” and “represents” should be “is” or “are”;
in claims 1-3, and 9 “a structure parenthesized in ()n” should be the “the structure parenthesized in ()n”;
in claims 4 and 10, “R6A or R7A” should be “R6A and R7A”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
In claims 1-4, 6-10, and 12-13 each instance of “>” is indefinite because the “>” is generally understood as a greater than sign and the meaning is not understood in this case.
In claims 1-4, 6-10, and 12-13, the recitations “X1 to X3”, “R1 to R3”, “R8 to R10”, “Y1 to Y3”, “Z1 to Z3”, “W1 to W3”, “R1 to R7”, “X4-X9”, “R101 to R103”, “R6 to R10”, and “X1 to X9” are indefinite because it not clear if the recitations are intended to include variables numbers in between such as X2, R2, and R9.
In claims 2-4, and 9-10, the recitation of “described above” is indefinite because there is no description of above in the same claim for those variables.
In claim 1, the recitation of “a substituent” indefinite because it is not clear what qualifies as a substituent. The recitations of L3 and L4 in claim 1 are indefinite because L3 and L4 are not otherwise defined the claim.
In claim 2, the L3 and L4 in general formula (II) are not defined the claim except at a proviso rendering the general formula (II) indefinite.
, In claims 12 and 13, the recitation of “General Formula (I)” is indefinite because the claims depend to the claim 9 that requires a General Formula (V).
Claims 5, 11, and 14-15 depend to one of those claims and fall therewith.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Geng (RIT thesis; published 2017; see IDS filed 10 Apr. 2024), in view of Lee et al. (US 2006/0014966A1; published 19 Jan. 2006; see attached 892).
Geng teaches the synthesis of polyproline spacers between NIR dye pairs for FRET to enhance photoacoustic imaging (see title). Geng teaches discovering an effective system of Forster Resonance Energy Transfer (FRET) composed of a near infrared fluorescent NIRF dye and NIR quencher (NIRQ) dye separated by a polyproline peptide spacer. Multiple polyproline spacers (di, tetra, octa) were synthesized and coupled to two NIRF dyes, Cy5.5 and IR770Ti using a modular synthetic approach developed by the group. Tetra and octaproline NIRF-NIRQ systems yield nearly complete FRET quenching (see iii). Geng teaches that it is optimal to choose NIR dyes in a range of absorption above 750 nm (pg. 5). The fluorescence of a higher wavelength dye can be cause by irradiating a lower wavelength dye. A second manner is which FRET can be utilized is for quenching emission of light (pg. 10). Peptides that are 11-14 amino acids in length were shown to offer an appropriate distance for quenching. TMAIs can be designed by the conjugation of the imaging agents to targeting agents that specifically bind to cancer cells (pg. 12). Geng teaches a embedding amino acids usually lysine by the modular approach. (pg. 15). The lysine is incorporated into a TMIA by use of peptide synthesis and the targeting group is added in the final step (pg. 16; scheme 2). Two dyes could be placed on two different amino acids with a spacer peptide chain to separate them (pg. 19). Geng teaches a FRET model system for fluorescence dyes (scheme 4, 15). Longer polyprolines may be used in the future (pg. 23). Geng teaches application of optimized distance by polyproline in quencher system (pg. 26). Geng teaches the compounds 21
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, 24
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, 27
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, and 30
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(schemes 18-21).
These compounds read in part on compounds of General Formula (I)
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wherein X1=X2=X3=CR2R3, R2=R3=H; La=Lb=bond; n=integer ≥2; and *=binding site. In addition, these compounds read on compounds of formula (II)
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wherein X1=X2=X3=CR2R3, R2=R3=H; n=integer ≥2; La=C(O); R4=R5=H; L1=NRA, RA=H; L2=L5=alkylene group; both M=IRdye (phosphor; 2 Ms=phosphor); m=1; L6=acyl group; R6=acyl or H (after deprotection); and R7=amino group. These compounds read in part on compounds of formula V
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wherein X1=X2=X3=CR2R3, R2=R3=H; X4=X5=X6=X7=X8=X9=CR102R103, R102=R103=H; n=integer ≥2; m=≥1; R6=acyl or H (after deprotection); and R7=amino group. These compounds in part read on compounds of formula (VI)
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X1=X2=X3=CR2R3, R2=R3=H; X4=X5=X6=X7=X8=X9=CR102R103, R102=R103=H; n=integer ≥2; m=integer ≥1; L12=L13=Lys (linking group); na=nb=integer 0 or more; R6A= acyl group; and R7A=H. These compounds read on compounds of formula (III)
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wherein X1=X2=X3=CR2R3, R2=R3=H; n=integer ≥2; s=t=u=0; LL1=C(O); R4=R5=H; H L2=L5=alkylene-NH-; both M=IRdye (phosphor; 2 Ms=phosphor); LL2=-NH-; L1=-NH-; R6=acyl group; L6=C(O); and R7=amino group. These compounds read on compounds of general formula (IV)
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wherein X1=X2=X3=CR2R3, R2=R3=H; n=integer ≥2; s=t=u=0; R4=R5=Y4=Y5=H; L2=L6=alkylene-NH-; both M=IRdye (phosphor; 2 Ms=phosphor); L7=CO; R6A=alkoxy group; L8=-NH-; and R7A=H.
Geng teaches dye aggregation (pgs. 42, 43, 44). The dual dye system could provide an stronger FRET effect than octaproline system with addition of D-alanine (pg. 49). Aggregation is influenced by the presence of polyproline when a second dye is present (pg. 55). Tetra- and octaproline NIRF-NIRQ dual dye systems both displayed highly effective FRET quenching (pg. 59).
Geng does not disclose a compound of formula I meeting the proviso that the structure in ()n has an R2 or R3 group including –(L-O)gRE or a compound of formula (II) wherein the structure in ()n has an R2 or R3 group including –(L-O)gRE and/or La, L3, or L4 has the substitute group including –(L-O)g-RE. Geng does not disclose a compound of formula (I) wherein at least one R2 is -NR8R9, wherein one of R8, or R9=-(L-O)RE. Geng does not disclose a compound of formulas (III) and (IV) provided that one of R1, R2, and R3 include a –(L-O)gRE which is not bonded to a phosphor or biological substance and one of R6A and R7A is a Q that is a carboxy substituent or a substituent capable of being bonded to solid support. Geng does not disclose a compound of formula (III) wherein one of s, t, or u is 1 or more and at least one of the Y1-3, Z1-3, or the W1-3 include the –(L-O)gRE group. Geng does not disclose a compound of formulas (V) or (VI) wherein one of X4, X5, and X6 has a L10-M and one of X7, X8, and X9 has a L11-M and one of X1, X2, and X3 having a group including –(L-O)gRE and wherein one of R6A or R7A=Q and Q=carboxy substituent or a substituent capable of being bonded to solid support optionally provided that the number of shortest linking atoms of L13 is ≤7. Geng does not disclose a substance obtained by bonding the compound of claim 1 to a biological substance optionally protein.
Lee et al. teach cell adhesion inhibitors (see title). An inhibitor containing polyethylene glycol can have advantageous properties (see abstract). Lee et al. teach the compounds
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(pg. 5) and
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(pgs. 22, 28). n is an integer such that the compound has a molecular weight between 400 and 70,000 ([0006]). Lee et al. teach amino functionalized proline ([0161]). Lee et al. teach that a stabilizing group can enhance pharmacokinetic or pharmacodynamic properties. The stabilizing group can a include a water soluble polymer, e.g. a PEG moiety. For example, an inhibitor having a PEG moiety can have greater water solubility, longer plasma circulating half-life, and a longer elimination half-life that related compound without a PEG moiety ([0048], [0098]-[0101])). Lee et al. teach converting hydroxyproline into an aminoproline ([0046]). Lee et al. teach fluorescence ([0103]-[0140, [0176]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the compounds of Geng (above polyprolines comprising at least lysines having FRET fluorophores attached to the lysine amino radicals) so that one or more prolines has an instant X2 that is CHR8, R8=NH-C(O) -(L-O)gRE where L=C2 alkylene, g= 1-24, and RE=Me to arrive at a compound of general formulas (I), (II), (III), and (IV) meeting the proviso that at least the R2 contained in the ()n is a group including the –(L-O)gRE as taught by Geng and Lee et al. because the one or more amino PEG substituted prolines would have been expected to enable improved water solubility, and enable a longer circulating half-life whereby preventing the use of co-solvents and aggregation and enabling biological use. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Geng so that one or instant R6A and R7A is a Q that is a carboxyl group or a substituent capable of being bonded to a biological substance as taught by Geng and Lee et al. because those substituents would have been expected to advantageously enable attachment to a targeting moiety. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Geng by further incorporating another lysine moiety to arrive at instant formulas (III) and (IV) such that one of s, t, and u is 1 and one of Z1-3=H, and one of W1-3=alkyl that includes the obvious –(L-O)gRE (PEG moiety) as taught by Geng and Lee et al. because those compounds would have been expected to enable equivalent FRET compounds prepared by a modular approach having enhance water solubility. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Geng by arriving a biological substance such as a peptide that is obtained by bonding the obvious compound of claim 1 to the biological substance as taught by Geng and Lee et al. because the bonding would have been expected to enable a targeted enhanced FRET conjugate having high water solubility.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify the compounds of Geng so that an amino substituted proline substitutes the lysine such that the FRET fluorophores connect to the amino substituted prolines at an optimal distance to arrive compounds of instant of instant formulas (V) and (VI) where L10 and L11 are divalent linking groups and M are the FRET pair and at least one instant R2 contained in the structure in ()n is a group including the obvious PEG of formula –(L-O)gRE as taught by Geng and Lee et al. because the amino substituted prolines replacements would have been expected to provide an equivalent molecular ruler peptide linker enabling an optimal distance between FRET pairs and advantageously water solubility and capable of an enhanced FRET. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify the one compounds of instant formulas (V) and (VI) so that one or R6A and R7A is a Q that carboxy groups, or a substituent capable of being bonded to a biological substance and the number of shortest linking atoms of the L12 or L13 is ≤7 as taught by Geng and Lee et al. because those substituents would have been expected to advantageously enable attachment to a targeting moiety at an optimal distance. The number of amino acids such as prolines and lysines in the polyproline spacer is a result effective variable that a person of ordinary skill in the art would have been motivated to optimize at the time of invention in order to arrive at an optimal spacer length with optimal hydrophilicity and FRET effects.
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 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 18/411,057, in view of Geng (RIT thesis; published 2017; see IDS filed 10 Apr. 2024), and Lee et al. (US 2006/0014966A1; published 19 Jan. 2006; see attached 892). This is a provisional nonstatutory double patenting rejection.
Claims 1-15 of copending Application No. 18/411,057 claims a compound comprising two or more phosphor moieties of which light absorption characteristics are equivalent to each other wherein the phosphor moieties are linked through a group including structure of General Formulas (I), (II), (III), (IV), (V) optionally wherein one of the conditions of Z1-Z3 are satisfied, (VI), and (VII) and provided that at least one of R6A and R7A represents Q and the shortest number of linking atoms of the L12 and L13 is 7 or less and wherein X1 to X3 are >CR2R3 and at least one R2 is NR8R9 and one of R8 and R9 include an anionic group and claim a biological substance obtained by bonding the compound of claim 1 to a biological substance optionally a protein
Claims 1-15 of copending Application No. 18/411,057 do not claim the claimed formulas provided that at least one of R1, R2, or R2 in the structure in parenthesized in ()n, ()na, or ()nb is a group including –(L-O)gRE or wherein one of Z1-Z3 is satisfied.
Geng teaches as discussed above.
Lee et al. teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-15 of copending Application No. 18/411,057 so that each of the structures parenthesized in ()n, ()na, or ()nb has a group including the –(L-O)gRE and optionally so the one of a Z1-3 include the –(L-O)gRE such that R2 that is a -NR8H where R8 is NH-C(O) -(L-O)gRE where L=C2 alkylene, g= 1-24, and RE=Me to arrive at compounds of general formulas as taught by Geng and Lee et al. because the one or more amino PEG substituted prolines would have been expected to enable improved water solubility, and enable a longer circulating half-life whereby preventing the use of co-solvents and aggregation and enabling biological use.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN R DONOHUE whose telephone number is (571)270-7441. The examiner can normally be reached on Monday - Friday, 8:00 - 5:00 EST.
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/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618
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