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’s election without traverse of Group I, claims 1, 11, 16-19, 26, 30, 32, 35-38, 40, 51, 52, 58, and 60, in the reply filed on 19 February 2026 is acknowledged, as well as the election of the following species:
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Claims 64 and 65 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 26, 30, and 32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 26, 30, and 32 are drawn to the embodiment of X being -O-G, unlike the elected species, in which X is -OH.
Claims 1, 11, 16-19, 26, 30, 32, 35-38, 40, 51, 52, 58, 60, 64, and 65 are pending; claims 26, 30, 32, 64, and 65 are withdrawn; and claims 1, 11, 16-19, 35-38, 40, 51, 52, 58, and 60 are examined herein on the merits.
Abstract
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it has fewer than 50 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claims 19 and 36 are objected to because of the following informalities:
Regarding claim 19, the limitation "each of" must be added after "relative to an otherwise identical compound in which."
Regarding claim 36, in the limitation "C1-C10 alkylcarbonate," the number 10 must be subscripted.
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.
Claims 16 and 19 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 16 recites the limitation "wherein the vinylic positions and allylic positions of Q, if present, are unsubstituted." It is unclear how if Q has allylic position(s), the vinylic positions and of Q can unsubstituted. For example, in the final structure of claim 51 (reproduced below), Q has an unsubstituted allylic position (methyl group), but the one of the vinylic positions of Q is substituted with the methyl group that provides the allylic position.
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Claim 19 is unclear because it treats Q as distinct from, and in addition to, R4, R5, R6 and R7. However, claim 1 previously recites that at least one of R4, R5, R6 and R7 is Q. This rejection can be overcome by removing both instances of "Q" from claim 19.
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 17-19, 35-38, and 40 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shabat (WO 2018/216013 A1; IDS), as evidenced by Coe ("Helquat Dyes: Helicene-like Push–Pull Systems with Large Second-Order Nonlinear Optical Responses," J. Org. Chem. 2016; previously cited).
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Regarding claims 1, 17, and 18, Shabat discloses a compound of Formula I (Shabat's Formula Ib, [0009], claim 1, copied above),
wherein
R1 and R2 taken together with the carbon to which they are attached provide a spirocyclic adamantane (Shabat's R2 and R3, abstract, [0006]-[0009], [0032], [0036], claims 4 and 10);
R3 is C1-C10 alkyl (Shabat's R1, [0009], [0031], [0036], claims 2 and 10);
R4 is H (Shabat's Formula Ib, [0009], claim 1);
R5 and R7 are selected from H and Q ("A represents one or two π* acceptor groups, each independently attached either ortho or para to the -Y-L-R4 group and selected from -CN or -CH=CH-E, wherein E is …," [0009], [0034]-[0036], claim 1);
R6 is H (Shabat's Formula Ib, wherein Shabat's A and R5 are ortho or para to the -Y-L-R4 group and Shabat's R5 can be H, [0033], [0034], thereby leaving the position meta to -Y-L-R4 group unassigned and implicitly H);
at least one of R5 and R7 is Q (Shabat's Formula Ib must contain at least one A, [0009], [0034]-[0036], claim 1);
Q is a π-conjugated electron donating group (discussed below) that is a C2 alkenyl substituted with an electron-donating group (A is -CH=CH-E, where E is 1,2,3,5,6,7-hexahydropyrido[3,2,l-ij] quinolin-9-yl; [0009]; Table 2, page 11, copied above; [0034]-[0036]; claims 1, 7, and 9); and
X is OH (Y is -O- and L is absent; R4 is H, [0009], [0037]).
Shabat teaches that A represents a π* acceptor group of the formula -CH=CH-E. However, this description is inaccurate for Shabat's choice of E being 1,2,3,5,6,7-hexahydropyrido[3,2,l-ij] quinolin-9-yl. The 1,2,3,5,6,7-hexahydropyrido[3,2,l-ij] quinolin-9-yl group of Shabat, which is also called a julolidinyl group, is electron-donating, as evidenced by Coe ("the stronger π-electron donating ability of the julolidinyl group vs 4-(dimethylamino)phenyl that is evident in…" page 1913, right col., second full para.). According, Shabat's disclosure of A being -CH=CH-E where E is 1,2,3,5,6,7-hexahydropyrido[3,2,l-ij] quinolin-9-yl is a disclosure of a π-conjugated electron donating group, as required by claim 1.
Regarding claim 19, Shabat's R5 is H ([0033], [0034]), and Shabat's A is one or two CH=CH-E, wherein E is 1,2,3,5,6,7-hexahydropyrido[3,2,l-ij] quinolin-9-yl," [0009], [0034]-[0036], claim 1). Given that Shabat's disclosure of -CH=CH-E where E is 1,2,3,5,6,7-hexahydropyrido[3,2,l-ij] quinolin-9-yl is electron donating, as set forth above regarding claim 1, Shabat discloses that the aromatic ring to which X, R4, R5, R6 and R7 attach is electron-enriched relative to an otherwise identical compound in which [each of] R4, R5, R6 and R7 is H.
Regarding claim 35, Shabat discloses that R3 is unsubstituted C1-C10 alkyl (Shabat's R1 is methyl, ethyl, or isopropyl, [0031]).
Regarding claims 36 and 37, Shabat discloses that one R5 and R7 is Q (A represents one or two π* acceptor groups, each independently attached either ortho or para to the -Y-L-R4 group and selected from -CN or -CH=CH-E, wherein E is …," [0009], [0034]-[0036], claim 1) and the other (Shabat's Formula Ib), as well as R4 (Shabat's Formula Ib, [0009], claim 1) and R6 (Shabat's Formula Ib, wherein Shabat's A and R5 are ortho or para to the -Y-L-R4 group and Shabat's R5 can be H, [0033], [0034], thereby leaving the position meta to -Y-L-R4 group unassigned and implicitly H), are H.
Regarding claim 38, Shabat discloses that R7 is Q ("A represents one or two π* acceptor groups, each independently attached either ortho or para to the -Y-L-R4 group and selected from -CN or -CH=CH-E, wherein E is …," [0009], [0034]-[0036], claim 1).
Regarding claim 40, Shabat discloses the phenyl group of Formula II as set forth above regarding claims 36-38. Shabat further discloses the 2-adamantyl group of Formula II, where R10 and R11 are each H, in the disclosure that Shabat's R2 and R3, together with the carbon atom to which they are attached, form adamantly and that the Shabat's probes are based on the Schapp's adamantylidene-dioxetane probe, which have a 2-adamantyl group (abstract, [0006]-[0009], [0032], [0036], claims 4 and 10).
Claim Rejections - 35 USC § 102/103
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.
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.
Claims 1, 11, 16-19, 35-37, and 40 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Wang (US 5,603,868; IDS).
Regarding claims 1, 11, 16-18, and 35-38, Wang discloses a compound of Formula (II) (col. 4, lines 49-67):
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, wherein R1 of Formula (II) is unsubstituted adamantyl in a more preferred embodiment (col. 4, line 64), R2 is an unsubstituted C1-10 alkyl or C1-10 alkyl substituted with halogen, hydroxy, amino, thio, or carboxylate (col. 4, lines 44-48), and OX is a chemically labile group wherein the removal of X by an activating agent results in the formation of an aryl oxide intermediate (col. 4, lines 37-39), where in the description of Scheme I, X is referred to as a "protecting group" (col. 6, line 31), and "In a more preferred embodiment…R3 is at position 4 and is C1-C10-alkyl" (col. 4, line 65).
Wang provides the following special definition of a chemically labile group (col. 9, lines 63-67; bolding added):
"Chemically labile group" is a group capable of forming an anion upon enzymatic or chemical cleavage. Chemically labile groups include but are not limited to hydroxyl, alkyl or aryl ester, inorganic oxyacid salt, alkyl or aryl silyloxy and oxygen-pyranoside.
Wang provides the following special definition of C1-C10-alkyl (col. 9, lines 27-29; bolding added):
"C1-C10-alkyl" refers to saturated or unsaturated, branched or straight chain alkyl groups having 1 to 10 carbon atoms, e.g., methyl, n-butyl or decyl.
According to Wang's special definition, a C2-alkyl can be the unsaturated group ethenyl, which is -CH=CH2.
Accordingly, the choice of Wang's R3 being C2-alkyl that is (unsaturated) ethenyl provides the compound of Formula I of claims 1, 11, 16-18, and 35-38, wherein R1 and R2 taken together with the carbon to which they are attached provide a C5-10 cycloalkyl ring that is spirocyclic adamantane; R3 is unsubstituted C1-10 alkyl or C1-10 alkyl substituted with halogen, hydroxy, amino, thio, or carboxylate; R4-R6 are H; R7 is Q; Q is a π-conjugated electron donating group that is an unsubstituted vinyl; X is -OH (when the chemically labile group is hydroxyl) or X is -O-G and G is an alcohol protecting group (when the chemically labile group is the non-hydroxyl options of Wang's special definition).
Regarding the question of whether a generic disclosure will anticipate a claimed species, MPEP 2131.02, III teaches the following (bolding added):
"[W]hether a generic disclosure necessarily anticipates everything within the genus … depends on the factual aspects of the specific disclosure and the particular products at issue." Sanofi-Synthelabo v. Apotex, Inc., 550 F.3d 1075, 1083, 89 USPQ2d 1370, 1375 (Fed. Cir. 2008). See also Osram Sylvania Inc. v. American Induction Tech. Inc., 701 F.3d 698, 706, 105 USPQ2d 1368, 1374 (Fed. Cir. 2012) ("how one of ordinary skill in the art would understand the relative size of a genus or species in a particular technology is of critical importance").
A reference disclosure can anticipate a claim even if the reference does not describe "the limitations arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination." Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381, 114 USPQ2d 1250, 1254 (Fed. Cir. 2015) (quoting In re Petering, 301 F.2d 676, 681(CCPA 1962)). In Kennametal, the challenged claim was to a cutting tool requiring a ruthenium binding agent with a physical vapor deposition (PVD) coating. Claim 5 of the reference disclosed all the elements of the claimed coated cutting tool, however, ruthenium was one of five specified binding agents and the claim did not specify a particular coating technique. The specification of the reference disclosed PVD as one of three suitable coating techniques. The Federal Circuit stated that the reference’s "express ‘contemplat[ion]’ of PVD coatings provided sufficient evidence that a reasonable mind could find that a person of skill in the art… would immediately envisage applying a PVD coating. Thus, substantial evidence supports the Board's conclusion that [the reference] effectively teaches 15 combinations, of which one anticipates pending claim 1. Though it is true that there is no evidence in [the reference] of ‘actual performance’ of combining the ruthenium binder and PVD coatings, this is not required." Kennametal, 780 F.3d at 1383, 114 USPQ2d at 1255 (citations omitted).
When a claimed compound is not specifically named in a reference, but instead it is necessary to select portions of teachings within the reference and combine them, e.g., select various substituents from a list of alternatives given for placement at specific sites on a generic chemical formula to arrive at a specific composition, anticipation can only be found if the classes of substituents are sufficiently limited or well delineated. Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990). If one of ordinary skill in the art is able to "at once envisage" the specific compound within the generic chemical formula, the compound is anticipated. One of ordinary skill in the art must be able to draw the structural formula or write the name of each of the compounds included in the generic formula before any of the compounds can be "at once envisaged." One may look to the preferred embodiments to determine which compounds can be anticipated. In re Petering, 301 F.2d 676, 133 USPQ 275 (CCPA 1962).
In In re Petering, the prior art disclosed a generic chemical formula "wherein X, Y, Z, P, and R'- represent either hydrogen or alkyl radicals, R a side chain containing an OH group." The court held that this formula, without more, could not anticipate a claim to 7-methyl-9-[d, l'-ribityl]-isoalloxazine because the generic formula encompassed a vast number and perhaps even an infinite number of compounds. However, the reference also disclosed preferred substituents for X, Y, Z, P, R, and R' as follows: where X, P, and R' are hydrogen, where Y and Z may be hydrogen or methyl, and where R is one of eight specific isoalloxazines. The court determined that this more limited generic class consisted of about 20 compounds. The limited number of compounds covered by the preferred formula in combination with the fact that the number of substituents was low at each site, the ring positions were limited, and there was a large unchanging structural nucleus, resulted in a finding that the reference sufficiently described "each of the various permutations here involved as fully as if he had drawn each structural formula or had written each name." The claimed compound was 1 of these 20 compounds. Therefore, the reference "described" the claimed compound and the reference anticipated the claims.
Given that the structure of Formula II of Wang provides a limited number of compounds that vary at position R3, given that in "a more preferred embodiment… R3 is at position 4 and is C1-C10-alkyl," and given that Formula II has a large unchanging structural nucleus, under the first interpretation of Wang, it is held that one of ordinary skill in the art could draw the structural formula of each compound included in the more preferred embodiment of Formula II of Wang and therefore could "at once envisage" R3 being C2-alkyl, which according to the special definition can be the unsaturated group -CH=CH2, thereby anticipating the compounds of claims 1, 11, 16-18, and 35-38.
Under an alternative second interpretation, the compound of Formula I of claims 1, 11, 16-18, and 35-38, where Q is an unsubstituted vinyl, is held to be obvious over the more preferred embodiment of Formula II of Wang.
Regarding the obviousness of species when the prior art teaches a genus, MPEP 2144.08 teaches that factors to be considered include the number of species encompassed by the genus.
Given that the structure of Formula II of Wang provides a limited number of compounds that vary at position R3, and given that in "a more preferred embodiment… R3 is at position 4 and is C1-C10-alkyl," and given that Formula II has a large unchanging structural nucleus, in the alternative to anticipation, it would have been obvious to one of ordinary skill in the art before the time of filing to select from the disclosed choices of R3 of Formula II to provide, the compound of Formula I of claims 1, 11, 16-18, and 35-38.
Choosing from a finite number of identified, predictable solutions, with a reasonable expectation for success, is likely to be obvious to a person of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, E.).
Regarding claim 19, because CH=CH2 is an electron donating group and R4, R5, and R6 are each H, Wang discloses that the aromatic ring to which X, R4, R5, R6 and R7 attach is electron-enriched relative to an otherwise identical compound in which [each of] R4, R5, R6 and R7 is H.
Regarding claim 40, Wang's disclosure of Formula (II) where R1 of Formula (II) is unsubstituted adamantyl in a more preferred embodiment (col. 4, line 64) is a disclosure of Formula II of claim 40, where each of R10 and R11 is H. Because Wang's Formula (II) illustrates R1 as a cycle, the choice of R1 being an unsubstituted adamantyl must be a 2-adamantyl (as opposed to a 1-adamantyl) to satisfy valence rules, which matches Formula II of claim 40.
Claims 1, 11, 16-19, and 35-37 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Sparks (US 10,031,142; newly cited).
Regarding claims 1, 11, 16-18, 36, and 37, Sparks discloses a 1,2-dioxetane formed in situ from combination of an oxidant with an enol ether (claim 1, step c; compare with Figs. 1, 12, and 17), the enol ether having the following structure (claim 1, step b):
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, in which A and B together is
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, R1 is alkyl containing 1 or 2 carbon atoms (claim 2) or heteroaryl (claim 1), wherein T-OR2 is
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, where R2 is an enzyme-cleavable group (claim 1), and OR2 is phosphate (claim 2), and R3 is a "straight chain alkenyl containing 2 to 20 carbon atoms" (claim 1). When R3 is a straight chain alkenyl containing 2 carbon atoms, R3 is -CH=CH2.
Accordingly, the choice of Sparks's R3 being a straight chain alkenyl containing 2 carbon atoms provides the compound of Formula I of claims 1, 11, 16-18, 36, and 37, wherein R1 and R2 taken together with the carbon to which they are attached provide a C5-10 cycloalkyl ring that is spirocyclic adamantane; R3 is C1-10 alkyl or heteroaryl; three of R4-R7 are H and the remaining one is Q; Q is a π-conjugated electron donating group that is an unsubstituted vinyl; X is -O-G; and G is an alcohol protecting group; as formed in the in situ oxidation step of claim 1, step c of Sparks.
Further regarding claims 1, 11, 16-18, 36, and 37, Sparks discloses the following enol ether phosphate (col. 27, lines 29-49):
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Because the previous definition of R6 provided by Sparks is for a component of a divalent group L, the group "R6" in the above illustrated enol ether phosphate appears to be a typographical error for "R3," which was previously defined as being selected from a group that includes "straight chain alkenyl containing 2 to 20 carbon atoms" (col. 3, lines 19-21).
Sparks teaches that "Two enol ether phosphates were successfully converted to their corresponding 1,2-dioxetane alkaline phosphatase substrates by oxidation in aqueous, basic conditions" (col. 38, lines 6-8), thereby providing the claimed 1,2-dioxetane compound of Formula I.
Regarding the question of whether a generic disclosure will anticipate a claimed species, MPEP 2131.02, III provides a relevant teaching quoted in the rejection above based upon Wang, which is encorporated here by reference.
Given that the structure of claim 1 of Sparks (and the enol ether phosphate col. 27) provides a limited number of enol ether compounds that vary at position R3 (or R6) and have a large unchanging structural nucleus, under the first interpretation of Sparks it is held that one of ordinary skill in the art could draw the structural formula of each compound included in the structure of claim 1 of Sparks (and the enol ether phosphate col. 27) and therefore could "at once envisage" R3 (or R6) being -CH=CH2. The disclosed conversion of the enol ether to the corresponding 1,2-dioxetane provides the compound of Formula I of claims 1, 11, 16-18, 36, and 37, where Q is an unsubstituted vinyl.
Under an alternative second interpretation, the compound of Formula I of claims 1, 11, 16-18, 36, and 37, where Q is an unsubstituted vinyl, is held to be obvious over the structure of claim 1 of Sparks (and the enol ether phosphate col. 27).
Regarding the obviousness of species when the prior art teaches a genus, MPEP 2144.08 teaches that factors to be considered include the number of species encompassed by the genus. Given that the structure of claim 1 of Sparks (and the enol ether phosphate col. 27) provides a limited number of enol ether compounds that vary at position R3 (or R6) and have a large unchanging structural nucleus, in the alternative to anticipation, it would have been obvious to one of ordinary skill in the art before the time of filing to select from the disclosed choices of R3 to provide, after the disclosed oxidation, the compound of Formula I of claims 1, 11, 16-18, 36, and 37.
Choosing from a finite number of identified, predictable solutions, with a reasonable expectation for success, is likely to be obvious to a person of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, E.).
Regarding claim 19, because CH=CH2 is an electron donating group, Sparks discloses that the aromatic ring to which X, R4, R5, R6 and R7 attach is electron-enriched relative to an otherwise identical compound in which [each of] R4, R5, R6 and R7 is H.
Regarding claim 35, Sparks discloses that R3 is unsubstituted C1-C10 alkyl (claim 2; col. 16, lines 19-20).
Claim Rejections - 35 USC § 103
Claims 58 and 60 are rejected under 35 U.S.C. 103 as being unpatentable over Shabat.
Regarding claims 58 and 60, Shabat discloses a composition comprising the compound of claim 1, as set forth above in the rejection of claim 1 regarding Shabat's Formula Ib, where A is -CH=CH-E and E is 1,2,3,5,6,7-hexahydropyrido[3,2,l-ij] quinolin-9-yl.
Shabat does not explicitly disclose that this embodiment is substantially free of surfactants or is substantially free of the specific surfactants of claim 60.
However, Shabat teaches away from the use of surfactant: "Up until recently, in-vitro and in-vivo imaging assays could not be applied without the use of a surfactant or complex supramolecular systems" ([0006]). Moreover, in working examples of preparing other examples of Shabat's Formula Ib, the dyes are each synthesized without any surfactant, including any of specific surfactants of claim 60, and are purified by HPLC (pages 23-36).
For the benefit of preparing pure samples of the probe compounds, it would have been obvious to one of ordinary skill in the art before the time of filing that Shabat's embodiment of Formula Ib, where A is -CH=CH-E and E is 1,2,3,5,6,7-hexahydropyrido[3,2,l-ij] quinolin-9-yl is prepared with sufficient purity, such as by using HPLC, such that the composition is substantially free of surfactants, including the specific surfactants of claim 60.
Claims 51, 52, 58 and 60 are rejected under 35 U.S.C. 103 as being unpatentable over Wang.
Regarding claims 51 and 52, Wang discloses the compounds of claims 1, 11, 16-19, 35-37, and 40, as set forth in the rejections above, wherein R3 is unsubstituted C1-10 alkyl or C1-10 alkyl substituted with halogen, hydroxy, amino, thio, or carboxylate; R4-R6 are H; R7 is Q; Q is a π-conjugated electron donating group that is an unsubstituted vinyl; X is -OH (when the chemically labile group is hydroxyl) or X is -O-G and G is an alcohol protecting group (when the chemically labile group is the non-hydroxyl options of Wang's special definition).
Wang further discloses the embodiment of Formula (IV) (copied below), where R2 is methyl (col. 5, line 43) and R4 can be zero groups or can be hydrogen (col. 5, lines 19-21).
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Wang fails to disclose, with sufficient specificity to anticipate, a single embodiment of the sixth compound of claim 51, which is also the third compound of claim 52 (copied below).
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However, as noted above, Wang separately discloses the choice of each of the moieties of this compound, including the choice of R3 being unsaturated ethenyl at position 4 and the chemically label group OX being hydroxyl.
Given that the structure of Formula II of Wang provides a limited number of compounds that vary at position R3, given that in "a more preferred embodiment… R3 is at position 4 and is C1-C10-alkyl," given that in Formula IV R2 is methyl, and given that Formulae II and IV have a large unchanging structural nucleus, it would have been obvious to one of ordinary skill in the art before the time of filing to select from the disclosed choices of R2 , R3, and OX of Formula II and IV to provide the sixth compound of claim 51, which is also the third compound of claim 52.
Choosing from a finite number of identified, predictable solutions, with a reasonable expectation for success, is likely to be obvious to a person of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, E.).
Regarding claims 58 and 60, Wang discloses a composition comprising the compound of claim 1, as set forth above in the rejection of claim 1.
Wang does not explicitly disclose that this embodiment is substantially free of surfactants or is substantially free of the specific surfactants of claim 60.
However, in working examples of preparing other examples of Wang's dioxetanes, the compounds are each synthesized without any surfactant, including any of specific surfactants of claim 60, and the enol ether synthetic precursors are purified by silica gel chromatography (col. 22, lines 59-61) or silica gel preparative TLC (col. 23, lines 32-35).
For the benefit of preparing pure samples of the probe compounds, it would have been obvious to one of ordinary skill in the art before the time of filing that Wang's preferred embodiment of Formula II, where R3 being unsaturated C2-alkyl, with sufficient purity, such as by purifying a synthetic precursor, such that the composition is substantially free of surfactants, including the specific surfactants of claim 60.
Claims 38, 40, 51, 52, 58, and 60 are rejected under 35 U.S.C. 103 as being unpatentable over Sparks.
Regarding claims 38, 40, and 51, Sparks discloses a composition comprising the compound of claim 1, as set forth above in the rejection of claim 1. Regarding claims 40 and the fifth structure of 51 (reproduced below), Sparks discloses that A and B together form 2-adamantyl (claim 1, col. 2, lines 24-44). Regarding the fifth structure of 51, Sparks discloses that the position meta to the dioxetane group (X in Formula I) is -OP(O)O2Na2 (Fig. 1; col. 27, lines 29-49) and that R1 (R3 in Formula I) is methyl (alkyl containing 1 carbon atom, col. 2, lines 54-56).
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Regarding claims 38, 40, and 51, Sparks does not disclose that the embodiment where R3 (or R6) is -CH=CH2 places R3 (or R6) para to the dioxetane group. In other words, while Sparks discloses that R3 (or R6) is located at one of positions R4, R5, R6 and R7, Sparks does not specifically disclose that -CH=CH2 is located at R7, as required by claims 38 and 40 and by the fifth structure of claim 51.
Choosing from a finite number of identified, predictable solutions, with a reasonable expectation for success, is likely to be obvious to a person of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, E.).
Given that the R3 (or R6) substituent of Sparks has a finite number of possible ring substitution positions, it would have been obvious to one of ordinary skill in the art before the time of filing to select the para position from among the possible ring substitution choices of R3 (or R6).
Regarding claim 52 and its third structure (reproduced below), an enol ether precursor is obvious over Sparks, as set forth above in the rejection of claim 51, where A and B together form 2-adamantyl, R1 is methyl, -CH=CH2 is located at the R7 position of Formula I, and a phosphate group is located at the X position of Formula I.
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Sparks further discloses an oxidation embodiment (Method A) where the phosphate enol ether is dephosphorylated prior to oxidation of the enol ether to form the 1,2-dioxetane (Fig. 12, reproduced below; Example 10, col. 40, lines 1-67), thereby forming a 1,2-dioxetane with a hydroxyl group at the X position of Formula I. Sparks teaches that this Method A provides the oxidation step as an assay "stop" solution in an enzyme assay application (Example 10).
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For the benefit of using the oxidation step as an assay "stop" solution in an enzyme assay application, it would have been obvious to one of ordinary skill in the art before the time of filing to oxidize the phosphate enol ether of Sparks, where R3 (R6) is -CH=CH2 and is located at R7, according to Method A of Sparks, thereby providing the dephosphorylated 1,2-dioxetane that is the third structure of claim 52.
Regarding claims 58 and 60, Sparks discloses a composition comprising the compound of claim 1, as set forth above in the rejection of claim 1.
Sparks does not explicitly disclose that this embodiment is substantially free of surfactants or is substantially free of the specific surfactants of claim 60.
Dependent claim 15 of Sparks recites the option of said aqueous solution further comprising an enhancer that is a polymeric quaternary ammonium salt or a polymeric quaternary phosphonium salt. The specification of Sparks teaches that the enhancer may be a component of the reaction mixture (i.e., an optional component). However, Sparks does not teach that the enhancer must be a component of the reaction mixture, or that the enhancer must be a surfactant, as opposed to an acceptor dye. Claim 1 recites that a reaction mixture is formed in step (e) by contacting the enzyme complex with the aqueous solution comprising the in situ generated 1,2-dioxetane enzyme substrate obtained in step (c). The rejection of claim 1 relies upon the in situ formation of the 1,2-dioxetane in step (c) rather than the 1,2-dioxetane starting material of step (e). In Example 8, Sparks discloses a method of converting enol ether to their corresponding 1,2-dioxetane alkaline phosphatase substrates by oxidation in aqueous, basic conditions without an added enhancer (col. 38, lines 1 to 40). The oxidation method disclosed by Sparks in col. 38, lines 1 to 40 occurs in a composition that is substantially free of surfactants or is substantially free of the specific surfactants of claim 60. Sparks teaches that the "reaction cleanly gave one product" (col. 38, lines 39-40).
For the benefit of using a known method of oxidizing an enol ether to a 1,2-dioxetane that cleanly gives one product, it would have been obvious to one of ordinary skill in the art before the time of filing that the relied upon enol ether embodiment of Sparks, where R3 is a straight chain alkenyl containing 2 carbon atoms, is oxidized according to the model oxidation conditions of col. 38, lines 1 to 40 such that the composition comprising the in situ generated 1,2-dioxetane is substantially free of surfactants, including the specific surfactants of claim 60.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Bronstein (US 5,538,847) discloses 1,2-dioxetanes of structure (I) (copied below), where Z is an electron-withdrawing or an electron-donating group (col. 4, lines 53-56). Bronstein teaches that the selection of an electron-withdrawing or an electron-donating group Z can alter the kinetics of the chemiluminescent reaction of the dioxetanes, as well as the signal intensity, or quantum yield of the chemiluminescent reaction (abstract; col. 3, lines 48-53).
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Renard (US 2009/0041669) discloses 1,2-dioxetanes of formula (Vc) ([0131], copied below), where R1 is a C1-C6 alkoxy radical ([0103]), and R11 is an "aryl radical" ([0110]). Renard provides a special definition of "aryl radical" ([0053]) and teaches that examples of aryl radicals include thiophene ([0054]).
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHELLE ADAMS whose telephone number is (571)270-5043. The examiner can normally be reached M, T, Th, and F, 12-4 P.M.
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/MICHELLE ADAMS/ Examiner, Art Unit 1797
/JENNIFER WECKER/ Primary Examiner, Art Unit 1797
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