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 .
Response to Amendment
Amendments to the abstract, specification, and claims filed on 23 October 2025 are acknowledged. Claims 1, 3-5, and 12-14 are amended. Claims 1-27 and 29 are pending; claims 10, 11, 16-27, and 29 are withdrawn; and claims 1-9 and 12-15 are presented herein for examination on the merits.
In response to the amendments filed on 23 October 2025, the objection to the abstract is withdrawn; the objections to the specification are withdrawn; the objections to the claims are partially withdrawn and supplemented; rejections under 35 USC 112(a) are added; the rejections under 35 U.S.C. 112(b) are partially withdrawn and supplemented; the rejections under 35 U.S.C. 102(a)(1) have been withdrawn; rejections under 35 U.S.C. 103 are added; and the double patenting rejection is withdrawn.
Claim Objections
Claims 1 and 12 are objected to because of the following informalities:
Claim 1 recites the limitation "wherein the standard composition is added to the sample containing the unknown carbohydrate and/or carbohydrate mixture composition." The indefinite article "a" is needed before "carbohydrate mixture composition," assuming that the limitation is meant to be interpreted as "wherein the standard composition is added to the sample containing the unknown carbohydrate and/or the standard composition is added to a carbohydrate mixture composition." Refer to the rejections under 35 USC 112(b) for an alternative interpretation of this limitation.
Claim 1 recites the limitation "one of R1 or R2 groups," which lacks number agreement.
Regarding claim 12, the "n" within the limitation "(CH2)n" must be subscripted.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-9 and 12-14 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention.
The examiner respectfully reminds the Applicant that according to MPEP §2163:
"2163.02. Standard for Determining Compliance with Written Description Requirement:
The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, “does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed.” In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon “reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter.” Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)). Whenever the issue arises, the fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991). An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was “ready for patenting” such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the University of California v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharmaceutical, 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by “whatever characteristics sufficiently distinguish it”).
(I)
Independent claim 1 has been amended to recite the limitation "one of R1 or R2 groups may be a carbonate or carbamate derivative (CH2)mOCOOR4 or (CH2)mNHCOOR4,"
Dependent claims 12 and 13 have been amended to recite a similar limitation.
The original disclosure does not contain the limitation "(CH2)mNHCOOR4." This is new matter.
Dependent claims 2-9 and 12-14 are rejected under 35 U.S.C. 112(a) for inheriting deficiencies of independent claim 1.
(II)
Independent claim 1 has been amended to recite the limitation "wherein the linker L may be divalent or polyvalent."
The original disclosure does not contain the word "polyvalent." This is new matter.
For purposes of this rejection, "polyvalent" is interpreted to mean "having a valence of three or more." The limitation that the linker L may be polyvalent is contradicted by the original disclosure of the L of Formula B, which is illustrated as being divalent.
Dependent claims 2-9 and 14 are rejected under 35 U.S.C. 112(a) for inheriting deficiencies of independent claim 1.
(III)
Independent claim 1 has been amended to recite the following indefinite limitation: "with the proviso that in all compounds represented by Formula B three or six negatively charged groups are present in the residues X of Formula B under basic conditions, and these negatively charged groups represent at least partially deprotonated residues of ionizable groups selected from the following: OH, … OSO3H…"
Dependent claims 12 and 13 have been amended to recite similar limitations.
As noted below in the rejections under 35 USC 112(b), it is unclear whether (i) each X has three or six negatively charged groups or (ii) Formula B has three or six negatively charged groups. For purposes of this rejection, interpretation (ii) is applied.
The amendments to recite six negatively charged groups selected from OH and OSO3H are not supported by the original disclosure and are new matter.
The specification provides no general teaching that the "ionizable groups" that are somehow related to the "three or six negatively charged groups" are OH or OSO3H.
Regarding the choice of the ionizable groups being OH, the closest written description support is found in the teaching that X can be "consisting of…hydroxyalkyl (CH2)nOH" (original claim 1). The transitional phrase "consisting of" closes X to unrecited elements (see MPEP 2111.03, II). Accordingly, the teaching that X consists of hydroxyalkyl (CH2)nOH supports three "negatively charged groups are present in the residues X of Formula B under basic conditions." However, the original disclosure does not teach that X includes two hydroxyalkyl (CH2)nOH, thereby providing six "negatively charged groups are present in the residues X of Formula B under basic conditions."
Moreover, specific examples of Formula B were disclosed, specifically compounds 7-R, 13a, 13b, 16, and 18 (original claim 15). Each of compounds 7-R, 13a, 13b, 16, and 18 corresponds to Formula B with each L-X or X comprising -(CH2)n-OH. However, compounds 7-R, 13a, 13b, 16, and 18 do not provide written description support for the entire scope of Formula B, including the full scope of R1, R2, and L recited in claim 1, or for the limitation regarding "six negatively charged groups."
Regarding the choice of the ionizable groups being OSO3H, the closest written description support is found in the teaching that X can be "consisting of…alkyl sulfate ((CH2)nOSO3H)" (original claim 1). The transitional phrase "consisting of" closes X to unrecited elements (see MPEP 2111.03, II). Accordingly, the teaching that X consists of alkyl sulfate ((CH2)nOSO3H) supports three "negatively charged groups are present in the residues X of Formula B under basic conditions." However, the original disclosure does not teach that X includes two alkyl sulfate ((CH2)nOSO3H), thereby providing six "negatively charged groups are present in the residues X of Formula B under basic conditions."
Dependent claims 2-9 and 12-14 are rejected under 35 U.S.C. 112(a) for inheriting deficiencies of independent claim 1.
Therefore, the Applicants did not show possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention, by description of an actual reduction to practice, or by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention.
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 1-9 and 12-15 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 1 recites the limitation "A method for an automated determination and/or automatic identification of i) carbohydrates and/or ii) carbohydrate mixture composition pattern profiling." It is unclear what subsequent limitations, if any, modifies "automated determination." In other words, does the limitation "of i) carbohydrates and/or ii) carbohydrate mixture composition pattern profiling" only modify "automatic identification"? Or does the limitation "of i) carbohydrates and/or ii) carbohydrate mixture composition pattern profiling" also modify "automatic determination"?
Claim 1 recites the limitation "said carbohydrate(s)" in step b). There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitation "the migration/retention time(s) of said carbohydrate(s) and the standard of known composition" in step d). There is insufficient antecedent basis for this limitation in the claim. Moreover, given that "the migration/retention time(s)" can be singular or plural, it is unclear whether "the migration/retention time(s) of" also refers to the standard of known composition. Does a single migration/retention time characterize both "said carbohydrate(s) and the standard of known composition"?
Claim 1 recites the limitation "fluorescence induced fluorescence detection" in step d). It is completely unclear what is meant by fluorescence induced fluorescence, which does not appear to be a term of art, and which is not used by the specification.
Claim 1 recites the limitation "these migration/retention time index or indices of the carbohydrate(s)" in step f). There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitation "the carbohydrate mixture composition pattern" in step g). There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitations "the sample containing the unknown carbohydrate and/or carbohydrate mixture composition" and "the unknown carbohydrate and/or carbohydrate mixture composition." There is insufficient antecedent basis for these limitations in the claim.
Beginning with the introduction of Formula B on page 23, claim 1 is replete with indefinite limitations and informalities. Accordingly, the intended scope of Formula B is unclear, as elaborated below. It is unclear where the definitions of each of the variable groups R1 or R2 groups stop and start. The scope of the R1 and R2 groups must either be consolidated to a single location, or alternative definitions of the R1 and R2 groups must be clearly separated into alternative groupings by the conjunction "or." Moreover, given that the definitions appear to be preceded by optional language such as "may," "can," or "preferably," it is unclear what structure is actually required for the variable groups of the formulae.
The use of the modal verbs "may" and "can" as recited in claims 1, 3, and 12-14 is indefinite because it is unclear whether the subsequent limitations are optional limitations. For purposes of evaluating the prior art, a limitation preceded by "may" or "can" is interpreted as an optional limitation.
Claim 1 recites the limitation "deuteron-substituted alkyl." The meaning of this limitation is unclear, given that a deuteron is the nucleus of deuterium. For purposes of evaluating the claim under 35 USC 112(a), this limitation is interpreted as "deuterium-substituted alkyl."
Claim 1 recites the limitation "R1---R2." There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitation "R1---R2 may form a four-, five, six-, or seven-membered non-aromatic carbocycle with an additional primary amino group NH2." There is insufficient antecedent basis for this limitation "an additional primary amino group NH2" in the claim.
Claim 1 recites the limitation "this cycle." There is insufficient antecedent basis for this limitation in the claim because the immediately preceding limitation is "…carbocycle."
Claim 1 recites the limitation "R1---R2 may form a four-, five, six-, or seven-membered non-aromatic heterocycle with an additional heteroatom such as O, N or S included into this heterocycle." It is unclear whether "additional heteroatom" requires that the heterocycle has at least two heteroatoms.
Regarding claims 1 and 12, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. Likewise, the term "preferably" as recited in claim 1 is indefinite. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). The term "preferably" prefaces a narrow limitation after a recitation of a broader limitation in the same claim. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 1, certain lines are not linked to any previous limitation, including the line beginning "a hydroxyalkyl group (CH2)mOH…" It is unclear how these limitations limit the claim.
Claim 1 in multiple instances describes a -(CH2)m- or -(CH2)n- subunit as being a straight or branched alkyl chain. The intended meaning of these limitations is completely unclear. How can (CH2)n be branched? Moreover, the limitations that -(CH2)m- or -(CH2)n- is straight chain appear to be a tautology.
Claim 1 recites the limitation "one of R1 or R2 groups may be a primary amino group to form aryl hydrazines Ar—NR6NH2." The meaning of this limitation is unclear. Is one of R1 or R2 groups a primary amino group that is capable of forming aryl hydrazines Ar—NR6NH2 in a subsequent reaction, or does aryl hydrazines Ar—NR6NH2" merely describe Formula B if one of R1 or R2 groups is a primary amino group? In the latter case, the limitation "…to form aryl hydrazines Ar—NR6NH2 " appears to be redundant. The limitation "to form aryl hydroxylamines Ar—NR7OH…" is indefinite for analogous reasons.
Claim 1 recites the limitation "the entire pyrene residue in Formula B." The scope of this limitation is unclear. How much of Formula B constitutes "the entire pyrene residue"?
Regarding claim 1, the use of parentheses, other than parentheses integral to chemical equations, renders the claim indefinite because it is unclear whether the limitations within parentheses are part of the claimed invention. For example, the parentheses within the limitations "(X = Br or I)" and "CH2CO, CF2CO)" render the limitations indefinite.
Claim 1 recites the limitation "the linker L." There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitation "wherein the linker L may be divalent or polyvalent." For purposes of this rejection, "the linker L" is interpreted as the L of Formula B. The specification does not contain the word "polyvalent" and for purposes of this rejection, "polyvalent" is interpreted to mean "having a valence of three or more." The limitation that the linker L may be polyvalent is indefinite because it contradicts the L of Formula B, which is previously illustrated as being divalent.
Claim 1 recites the limitation "single or multiple difluoromethyl (CF2)." The parenthetical "CF2" is unclear because CF2 is not synonymous with, or a subset of, the term "difluoromethyl."
Regarding claim 1, the meaning of "in any combinations, at any occurrence" is unclear.
Claim 1 recites the limitation "the length." There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitation "…and alkene or alkyne moieties in any combinations, at any occurrence, linear or branched, with the length ranging from C1 to C12." If "the length" is meant to refer to "alkene or alkyne moieties," it is unclear how alkene or alkyne moieties can be C1.
Claim 1 recites the limitation "the linker L may also comprise or contain a residue of 1,3,5-triazine, thus providing two attachment points for group X." The meaning of "thus providing two attachment points for group X" is completely unclear.
Claim 1 recites the limitation "the anion-providing moieties." There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitations "any of the moieties listed above for groups R1 and R2," "any type of linkage listed for group L," and "other substituents." There is insufficient antecedent basis for these limitations in the claim.
Claim 1 recites the limitation "the residues X." There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitation "in all compounds represented by Formula B three or six negatively charged groups are present in the residues X of Formula B under basic conditions." It is unclear whether (i) each X has three or six negatively charged groups or (ii) Formula B has three or six negatively charged groups. Under interpretation (i), a total of 9 or 18 negatively charged groups would be present in Formula B (multiplying 3, the number of X in Formula B, times three or six), while under interpretation (ii), a total of three or six negatively charged groups would be present in Formula B.
Claim 1 recites the limitation "and these negatively charged groups represent at least partially deprotonated residues of ionizable groups selected from the following…" It is unclear what is meant by partial deprotonation, or how a negatively charged group can be formed by partial deprotonation.
Dependent claims 2-9 and 12-15 are rejected under 35 U.S.C. 112(b) for inheriting deficiencies of independent claim 1.
Claim 3 recites the limitation "wherein the second sample may be added optionally to said first sample" in step c). Is the intended meaning of this limitation "the second sample optionally is added optionally to said first sample," which is redundant?
Claim 3 recites the limitation "electropherograms/chromatograms" in step d). It is unclear whether the slash indicates "and" or "or."
Claim 3 recites the limitations "the carbohydrate mixture composition" and "said sample" in step d). There is insufficient antecedent basis for these limitations in the claim.
Claim 3 recites the limitation "fluorescence induced fluorescence detection" in step d). It is completely unclear what is meant by fluorescence induced fluorescence, which does not appear to be a term of art, and which is not used by the specification.
Claim 3 recites the limitations "the identity and/or differences," "the carbohydrate mixture composition pattern profiles," and "the identity and/or differences between the carbohydrate mixture composition pattern profiles of the first and the second sample determined in step d" in step e). There is insufficient antecedent basis for these limitations in the claim.
Claim 3 recites the limitation "the identity and/or differences between the carbohydrate mixture composition pattern profiles of the first and the second sample." The meaning of "the identity … between the carbohydrate mixture composition pattern profiles of the first and the second sample" is unclear.
Claim 3 recites the limitation "a fluorescent dye as defined in claim 1." The scope of this limitation is unclear for the reasons set forth in the rejections of claim 1. Moreover, it is unclear whether claim 3 incorporates by reference all of the limitations of claim 1, including steps a) - g) of claim 1. A dependent claim must incorporate by reference all of the limitations of the claim from which it depends.
Claim 4 recites the limitations "the standard migration/retention time index or indices," "the obtained electropherogram or chromatogram," and "the obtained electropherogram or chromatogram of the first sample and the second sample" in step f). There is insufficient antecedent basis for these limitations in the claim.
Claim 4 recites the limitations "the identity and/or differences," "the carbohydrate mixture composition pattern profiles," "the identity and/or differences between the carbohydrate mixture composition pattern profiles of the first and the second sample," "the carbohydrates present in the sample," and "the sample" in step g). There is insufficient antecedent basis for these limitations in the claim.
Claim 4 recites the limitation "the identity and/or differences between the carbohydrate mixture composition pattern profiles of the first and the second sample." The meaning of "the identity … between the carbohydrate mixture composition pattern profiles of the first and the second sample" is unclear.
Claim 5 recites the limitation "the given standard migration/retention time index or indices of the at least two orthogonal standards." There is insufficient antecedent basis for this limitation in the claim.
Claim 7 recites the limitation "the identification." There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites the limitation "the glycosylation pattern." There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites the limitation "The method according to claim wherein…" The intended dependency of the claim is unclear. Claim 9 is henceforth treated as depending from claim 1.
Claim 9 recites the limitations "the components" and "the carbohydrate mixture." There is insufficient antecedent basis for these limitations in the claim.
Claim 12 recites the limitation "wherein Formula B is the fluorescent dye." This language is inconsistent with the language of independent claim 1, which recites that the fluorescent dye is selected from a group of compounds of a formula. In other words, claim 1 recites that the fluorescent dye is a compound and that Formula B characterizes a compound, rather than equating Formula B with a compound or the fluorescent dye. Claim 13 is indefinite for analogous reasons.
Claim 12 recites the limitation "n – 1-12." The meaning of the dash after "n" is unclear.
Regarding claim 12, the definitions that follow Formula C are indefinite for reasons analogous to those set forth regarding Formula B in claim 1.
Claim 12 recites the limitation "the (CH2)n-CH2 linker, with n=1-12, between the SO2 fragment and the residue X in Formula B may …." There is insufficient antecedent basis for the limitations "the SO2 fragment" and "the residue X" in the claim.
Claim 12 recites the limitation "the (CH2)n-CH2 linker, with n=1-12, between the SO2 fragment and the residue X in Formula B may represent a straight-chain, branched or cyclic group having 2-6 carbon atoms." It is completely unclear how (CH2)n-CH2 can represent a branched group. In order for (CH2)n-CH2 to represent a cyclic group, the limitation "the (CH2)n-CH2 linker" would lack proper antecedent basis. Moreover, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
Claim 12 recites the limitation "X = OH SH, COOH, SO3H, OSO3H, … with the proviso that in all compounds represented by Formula C three or six negatively charged groups are present in the residues X of Formula B under basic conditions, and these negatively charged groups represent at least partially deprotonated residues of ionizable groups selected from the following: OH SH, COOH, SO3H, OSO3H, … " The reference to compounds represented by Formula C and the residues X of Formula B is unclear. Moreover, given the recited choices of X, it is unclear how six negatively charged groups could be present in either the X of Formula B or Formula C. Claim 13 is indefinite for analogous reasons.
Regarding claim 13, the definitions that follow Formula D are indefinite for reasons analogous to those set forth regarding Formula B in claim 1 and those set forth regarding Formula C in claim 12.
Regarding claim 14, the overall structure and grammar of the definitions of "R1 and/or R2" are confusing and replete with errors.
Claim 14 recites the limitation "4,6-dihalo-1,3,5-triazinyl (C3N3X2) where halogen X." There is insufficient antecedent basis for X because independent claim 1 introduces X in Formula B and claim 14 previously introduces X in the parenthetical limitation C3N3X2.
Regarding claim 14, there does not appear to be a closing parenthesis to the limitation "(NHCSNHC6H4NH2."
Claim 14 recites the limitations "the integers m1, m2" and "the chain (CH2)m/n." There is insufficient antecedent basis for these limitations in the claim.
Claim 14 recites the limitation "the integers m1, m2 and n1, n2, n3, n4 independently range from 1 to 12 and from 0 to 12, respectively." It is unclear whether "integers" modifies "n1, n2, n3, n4." It is unclear to what "respectively" refers.
Claim 14 recites the limitation "the linked carboxylic acid residues and their reactive esters being straight, branched, saturated, unsaturated…" It is unclear how the previously recited general formulae of the linked carboxylic acid residues and their reactive esters can be branched or unsaturated or included into a carbocycle or heterocycle.
Claim 14 recites the limitation "R3 is …a nucleophile-reactive leaving group." It is unclear how R3 can be a nucleophile-reactive leaving group, as opposed to OR3.
Claim 15 recites the limitation "the compound of Formulae A to B." There is insufficient antecedent basis for this limitation in the claim, or of "Formula A." Compounds 6-H and 6-Me recited in claim 15 are outside the scope of Formula B. Accordingly, it is not clear whether claim 15 requires all of the limitations of independent claim 1.
Regarding claim 15, the use of parentheses to enclose definitions makes unclear whether the enclosed definitions are required by the scope of the claim.
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.
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, 2, 5-9, 13, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Rapp 2009 (US 2009/0288951; previously relied upon) in view of Vigh (US 2013/0224870; previously cited).
Regarding claim 1, Rapp 2009 discloses a method for an automated determination and/or automated identification of i) carbohydrates and/or ii) carbohydrate mixture composition pattern profiling comprising the steps of:
a) obtaining a sample containing at least one carbohydrate ([0018]);
b) labelling said carbohydrate(s) with a first fluorescent label ([0018]);
c) providing a standard of known composition labelled with a second fluorescent label ([0018], a standard DNA base pair ladder fluorescently labelled with a different tag than the carbohydrate samples, [0024]);
d) determining the migration/retention time(s) of said carbohydrate(s) and the standard of known composition using electrokinetic separation techniques combined with laser induced fluorescence detection ([0018]);
e) aligning the migration/retention time(s) to migration/retention time index or indices based on given standard migration/retention time index or indices of the standard ([0018]);
f) comparing these migration/retention time index or indices of the carbohydrate(s) with standard migration/retention time index or indices from a database ([0018]);
g) identifying or determining the carbohydrate(s) and/or the carbohydrate mixture composition pattern ([0018]),
wherein the standard composition is added to the sample containing the unknown carbohydrate and/or carbohydrate mixture composition, the first fluorescent label and the second fluorescent label are different (the standard DNA base pair ladder is fluorescently labelled with a different tag than the carbohydrate samples, [0024]).
and wherein the first fluorescent label or the second fluorescent label is a fluorescent dye having multiple ionizable and/or negatively charged groups, with the proviso that in the compound three negatively charged groups are present under basic conditions, and these negatively charged groups represent at least partially deprotonated residues of ionizable groups that are OH (8-amino-1,3,6-pyrenetrisulfonic acid, APTS, [0036]).
The structure of the fluorescent label of 8-amino-1,3,6-pyrenetrisulfonic acid (APTS) disclosed by Rapp 2009 is shown below and is an analog of Formula B, where L is a bond and X is OH.
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This fluorescent dye disclosed by Rapp 2009 differs from Formula B in not satisfying the claim 1 limitation that "the linker L … comprises at least one carbon atom."
In the analogous prior art of labeling carbohydrates ([0004], [0058], [0078], Fig. 43), Vigh discloses the following fluorescence labeling reagents ([0072], page 9; [0103], page 12).
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The above labeling reagents are each a compound of Formula B or a salt thereof and satisfy the claim 1 limitation that "the linker L … comprises at least one carbon atom."
Regarding the indefinite description of Formula B in claim 1, it is noted that all of the descriptions of R1 and R2 are preceded by the modal verb "may" or "can" and are interpreted as optional limitations, as discussed in the rejections under 35 USC 112(b).
Vigh provides the following teaching comparing the disclosed fluorescent labeling reagent to the previously known 8-amino-1,3,6-pyrenetrisulfonic acid (APTS) ([0103]):
The λmaxex of APTS around 420 nm. Consequently, excitation at 488 nm makes use of only about 4% of its maximum absorbance. For APTS, altering the electron withdrawing/donating capability of the sulfonic acid and amino groups may provide incremental bathochromic shifts to λmaxex. Thus, the inventors had the general objective for the development of a pyrene-based fluorophore, which was to build a complete fluorescent labeling reagent (fluorophore, tether and reactive group) out of the APTS core structure while preserving its desirable properties, as stated above, and simultaneously shifting its λmaxex towards 488 nm.
For the benefit of a fluorescent labeling reagent having a greater absorbance when excited at 488, it would have been obvious to one of ordinary skill in the art before the time of filing to modify the method of Rapp 2009 by replacing 8-amino-1,3,6-pyrenetrisulfonic acid (APTS) with a fluorescent labeling reagent of Formula B disclosed by Vigh.
The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.).
Regarding claim 2, Rapp 2009 discloses that the standard of known composition is a standard base pair ladder ([0024]).
Regarding claim 5, Rapp 2009 discloses that at least two orthogonal standards are added to the sample and orthogonal cross-alignment is performed based on the given standard migration/retention time index or indices of the at least two orthogonal standards ([0013], [0019], [0049]).
Regarding claim 6, Rapp 2009 discloses that the sample contains a mixture of carbohydrates ([0031]).
Regarding claim 7, Rapp 2009 discloses that the sample is an extraction of glycans and the method allows for the identification of a glycosylation pattern profile ([0031]).
Regarding claim 8, Rapp 2009 discloses that the glycosylation pattern of a glycoprotein is identified ([0041]).
Regarding claim 9, Rapp 2009 discloses that the components of the carbohydrate mixture are determined quantitatively ([0041]).
Regarding claim 13, the fluorescence labeling reagents disclosed in [0072], page 9 of Vign are an analog of Formula D, differing in having an R3 that is a methyl group rather that "C2H5," which is an ethyl group. The claimed ethyl substituent is a homologue of the disclosed methyl substituent. Homologues are a class of compounds differing only by a methylene linkage and possessing similar structures. In view of their closely related structures and the resulting expectation of similar properties, it would have been obvious to one of ordinary skill in the art before the time of the invention to replace the methyl R3 substituents of the fluorescence labeling reagents of Vign with an ethyl substituent.
Regarding the indefinite description of Formula D in claim 13, it is noted that all of the descriptions of R1 and R2 are preceded by the modal verb "may" or "can" and are interpreted as optional limitations, as discussed in the rejections under 35 USC 112(b).
Regarding claim 14, the fluorescence labeling reagents disclosed in [0103], page 12
of Vign are an example of Formula B, where R1 is H, and R2 is an alkyl group having an H atom of the alkyl group replaced by a reactive ester of the formula (CH2)n1COOR3 (where the leaving group of [0103] can be a N-hydroxysuccinimidate, alkoxy, etc., [0079]).
Claims 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Rapp 2013 (US 2013/0075258; previously relied upon) in view of Vigh (US 2013/0224870; previously cited).
Regarding claim 3, Rapp 2013 discloses a method for an automated carbohydrate mixture composition pattern profiling (claim 20, pages 5-6) comprising the steps of
a) providing a first sample containing a first carbohydrate mixture composition (step a);
b) labelling of said carbohydrate mixture composition with a first fluorescent label (step b);
c) providing a second sample containing a second carbohydrate mixture composition labelled with a second fluorescent label (step c);
d) generating electropherograms of the carbohydrate mixture composition of said sample using electrokinetic separation techniques combined with laser induced fluorescence detection (step d);
e) analyzing the identity and/or differences between the carbohydrate mixture composition pattern profiles of the first and the second sample (steps e and e), wherein the first fluorescent label of the first sample is different to the second fluorescent label of the second sample (claims 38-40).
Regarding the limitation "and wherein at least one of the first fluorescent label and the second fluorescent label is a fluorescent dye as defined in claim 1," Rapp 2013 discloses a fluorescent dye having multiple ionizable and/or negatively charged groups, with the proviso that in the compound three negatively charged groups are present under basic conditions, and these negatively charged groups represent at least partially deprotonated residues of ionizable groups that are OH (8-amino-1,3,6-pyrenetrisulfonic acid, APTS, [0036]).
The structure of the fluorescent label of 8-amino-1,3,6-pyrenetrisulfonic acid (APTS) disclosed by 2013 is an analog of Formula B, where L is a bond and X is OH. This fluorescent dye disclosed by Rapp 2009 differs from Formula B in not satisfying the claim 1 limitation that "the linker L … comprises at least one carbon atom."
In the analogous prior art of labeling carbohydrates ([0004], [0058], [0078], Fig. 43), Vigh discloses the following fluorescence labeling reagents ([0072], page 9; [0103], page 12). These labeling reagents are each a compound of Formula B or a salt thereof and satisfy the claim 1 limitation that "the linker L … comprises at least one carbon atom."
Regarding the indefinite description of Formula B in claim 1, it is noted that all of the descriptions of R1 and R2 are preceded by the modal verb "may" or "can" and are interpreted as optional limitations, as discussed in the rejections under 35 USC 112(b).
Vigh provides the following teaching comparing the disclosed fluorescent labeling reagent to the previously known 8-amino-1,3,6-pyrenetrisulfonic acid (APTS) ([0103]):
The λmaxex of APTS around 420 nm. Consequently, excitation at 488 nm makes use of only about 4% of its maximum absorbance. For APTS, altering the electron withdrawing/donating capability of the sulfonic acid and amino groups may provide incremental bathochromic shifts to λmaxex. Thus, the inventors had the general objective for the development of a pyrene-based fluorophore, which was to build a complete fluorescent labeling reagent (fluorophore, tether and reactive group) out of the APTS core structure while preserving its desirable properties, as stated above, and simultaneously shifting its λmaxex towards 488 nm.
For the benefit of a fluorescent labeling reagent having a greater absorbance when excited at 488, it would have been obvious to one of ordinary skill in the art before the time of filing to modify the method of Rapp 2013 by replacing 8-amino-1,3,6-pyrenetrisulfonic acid (APTS) with a fluorescent labeling reagent of Formula B disclosed by Vigh.
The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.).
Regarding claim 4, Rapp 2013 discloses
f) comparing the standard migration/retention time index or indices calculated from the obtained electropherogram of the first sample and the second sample (claim 21); and
g) analyzing the identify and/or differences between the carbohydrate mixture composition pattern profiles of the first and second sample, wherein standard migration/retention time index or indices of the carbohydrates present in the sample are calculated based on internal standards of known composition (claim 29) labelled with a third fluorescent label (" orthogonal internal standards of known composition," claim 29, [0031]).
Response to Arguments
Applicant's arguments filed on 23 October 2025 have been considered and are not fully persuasive and/or are moot in view of the new grounds of rejection.
Applicant's arguments to not specifically traverse the maintained rejections under 35 USC 112(b). While addressing the rejections under 35 USC 112(b), Applicant states "The undersigned brings to the attention of the Examiner US Patent 12,174,197…To address all of the issues raised for indefiniteness, the claims have been amended in the present case to specify the dye (the subject matter of US Patent 12,174,197) in the same manner." In response, the positions held by another examiner in another application are not binding on this application.
The rejections under 35 U.S.C. 102(a)(1) for anticipation by Rapp 2009 (US 2009/0288951) and Rapp 2013 (US 2013/0075258) have been withdrawn. As amended, claim 1 that the requires that the fluorescent dye is selected from the group consisting of compounds of Formula B or salts thereof. The fluorescent label of 8-amino-1,3,6-pyrenetrisulfonic acid disclosed by Rapp 2009 and Rapp 2013 differ from Formula B in not satisfying the claim 1 limitation that "the linker L … comprises at least one carbon atom." However, new rejections under 35 U.S.C. 103 based upon Rapp 2009 and Rapp 2013 have been added.
As a result of the amendments to claim 1, the double patenting rejection of claim 3 has been withdrawn.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to 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