DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
Receipt is acknowledged of Applicants’ amendment and remarks, filed on 10/17/2025, in which claims 1-2 and 18-19 are amended, claims 20-21 are newly added and claims 4-6 and 11 are canceled.
Claims 1-3, 7-10, and 12-21 are pending and are examined on the merits herein.
Priority
The instant application is a 371 of PCT/JP2020/026489 filed on 07/06/2020, which claims foreign priority to JP 2019-130188 filed on 07/12/2019.
Objections and Rejections Withdrawn
Applicant’s amendment and remarks, filed 10/17/2025, with respect that claim 19 is objected to because it is missing a period at the end of the claim has been fully considered and is persuasive, as appropriate correction has been made. This objection has been withdrawn.
Applicant’s amendment and remarks, filed 10/17/2025, with respect that claims 2 and 18-19 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 has been fully considered and is persuasive, as claim 2 has been amended to recite tris(hydroxymethyl)aminomethane and claims 18-19 have been amended to recite an amidation reaction solution having the pH of 7.7. This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 10/17/2025, with respect that claims 1-3, 8-10, and 12-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nishikaze as evidenced by the SDFCL N-methylmorpholine Safety Data Sheet has been fully considered and is persuasive, as the scope of claim 1 has been amended to limit that the amidation reaction solution does not contain a dehydration-condensation agent to be reacted with the lactone. This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 10/17/2025, with respect that claims 1 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Nishikaze as evidenced by the SDFCL N-methylmorpholine Safety Data Sheet has been fully considered and is persuasive, as the scope of claim 1 has been amended to limit that the amidation reaction solution does not contain a dehydration-condensation agent to be reacted with the lactone. This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 10/17/2025, with respect that claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Nishikaze in view of Lageveen-Kammeijer as evidenced by the SDFCL N-methylmorpholine Safety Data Sheet has been fully considered and is persuasive, as claim 5 has been canceled. This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 10/17/2025, with respect that claims 1-3, 7-10, and 12-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 10,712,338 in view of Nishikaze as evidenced by the SDFCL N-methylmorpholine Safety Data Sheet has been fully considered and is persuasive, as the scope of claim 1 has been amended to limit that the amidation reaction solution does not contain a dehydration-condensation agent to be reacted with the lactone. This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 10/17/2025, with respect that claim 5 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 10,712,338 in view of Nishikaze in view of Lageveen-Kammeijer as evidenced by the SDFCL N-methylmorpholine Safety Data Sheet has been fully considered and is persuasive, as claim 5 has been canceled. This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 10/17/2025, with respect that claims 1-3, 5, 7-10, and 12-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 1-16 of U.S. Patent No. 11,105,717 in view of Nishikaze has been fully considered and is persuasive, as the scope of claim 1 has been amended to limit that the amidation reaction solution does not contain a dehydration-condensation agent to be reacted with the lactone and claim 5 has been canceled. This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 10/17/2025, with respect that claims 1-3, 7-10, and 12-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,187,630 in view of Nishikaze has been fully considered and is persuasive, as the scope of claim 1 has been amended to limit that the amidation reaction solution does not contain a dehydration-condensation agent to be reacted with the lactone. This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 10/17/2025, with respect that claim 5 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,187,630 in view of Nishikaze in view of Lageveen-Kammeijer as evidenced by the SDFCL N-methylmorpholine Safety Data Sheet has been fully considered and is persuasive, as claim 5 has been canceled. This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 10/17/2025, with respect that claims 1-3, 5, 7-10, and 12-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,971,336 in view of Nishikaze has been fully considered and is persuasive, as the scope of claim 1 has been amended to limit that the amidation reaction solution does not contain a dehydration-condensation agent to be reacted with the lactone. This rejection has been withdrawn and claim 5 has been canceled. This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 10/17/2025, with respect that claims 1-3, 7-10, and 12-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,110,309 in view of Nishikaze has been fully considered and is persuasive, as the scope of claim 1 has been amended to limit that the amidation reaction solution does not contain a dehydration-condensation agent to be reacted with the lactone. This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 10/17/2025, with respect that claim 5 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,110,309 in view of Nishikaze in view of Lageveen-Kammeijer as evidenced by the SDFCL N-methylmorpholine Safety Data Sheet has been fully considered and is persuasive, as claim 5 has been canceled. This rejection has been withdrawn.
The following are new grounds of rejection necessitated by Applicant’s amendment, in which claim 1 is amended to include the limitation of claim 5 recite such that the amidation reaction solution does not contain a dehydration-condensation agent to be reacted with the lactone. The amended claims also recite the limitation “wherein the amine includes hydrazine, hydrazine derivatives, and hydroxylamine, and does not include ammonia or salts of ammonia”.
Claim Rejections - 35 USC § 112(b)
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 1-3, 7-10, and 12-21 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.
Claim 1 recites “wherein the amine includes” on line 16. It is not clear what amines are limited by this recitation, as amines are recited both in “primary amines” on line 7 and “when the alkalinizing agent is an amine” on line 12. For purposes of compact prosecution, this limitation will be interpreted as having antecedent basis in “when the alkalinizing agent is an amine” and thus as limiting the scope of the alkalinizing agent.
Claim 20 recites “the first agent” on line 2. There is insufficient antecedent basis for the limitation of “the first agent” in the claim. For purposes of compact prosecution, under broadest reasonable interpretation, the claim will be interpreted as “the first compound”, which has antecedent basis on line 6 of claim 1 and is a compound which is to be reacted with a lactone included in the glycan.
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.
Claims 1-3, 7-10, and 12-21 are rejected under 35 U.S.C. 103 as being unpatentable over Nishikaze (US 2018/0059094 A1; IDS 06/13/2022) in view of Lageveen-Kammeijer et. al (Nature Communications, 2019; PTO-892 06/18/2025) as evidenced by the CCI Ammonium Hydroxide Safety Data Sheet (2022; PTO-892 06/18/2025) and Lab-Chem ammonium hydroxide safety data sheet (2016; PTO-892).
Nishikaze teaches that glycosylation of peptide chains is one of the most important processes of post-translational modification, and that glycoproteins containing sugar chains attached to peptide chains are involved in various life phenomena [0002]. A sugar chain attached to a protein often has sialic acid, and analytical determination of the number of sialic acid residues and the linkage type of sialic acid is important in structural analysis of glycoproteins or glycopeptides [0003]. Sialic acid has α2,3-linked sialic acid and α2,6-linked sialic acid linkage isomers which have different biological properties and must be distinguished [0004].
Nishikaze discloses a method of preparing a sample for analysis of a glycoprotein or glycopeptide [0013] which comprises modification of a carboxy group of sialic acid of a sugar chain [0014]. In this modification α2,3-linked sialic acids are lactonized and α2,6-linked sialic acids forms an addition product, resulting in derivatives having different masses that can be distinguished by mass spectrometry. This allows determination of the presence or absence of sialic acid in the sugar chain of a glycoprotein or glycopeptide and identification of the linkage type of sialic acid simply by mass spectrometry with a high degree of accuracy [0023].
Nishikaze teaches that it is known that the lactonized product formed by intramolecular dehydration of an α2,3-sialyl sugar chain is unstable [0073] and that a second reaction is preformed after lactonization to achieve structural stabilization [0074]. This second reaction is a two-step process that modifies a lactonized product by a ring opening hydrolysis followed by an additional modification such as amidation. Amidation is preferred because an amine is highly reactive with the lactonized product, and an almost completely different modified product can be formed [0074]. Nishikaze provides teachings for selecting the amine to be used in this amidation. Nishikaze teaches that preferred amines include, among others, primary alkylamines such as ammonium salts, methylamine, ethylamine, and propylamine. Particularly preferred are methylamine and ethylamine or salts thereof [0077].
Example 4 of Nishikaze modifies free sugar chains released from fetuin, which has high α2,3-sialyl sugar chain content [0135]. Specifically, Nishikaze discloses Example 4-1 in which a sugar chain was modified using DIC and HOBt as a dehydration-condensation agent and isopropylamine hydrochloride as an amine hydrochloride. The sample was then purified using a GL-Tip Amide carrier and centrifugation with washing followed by a drying step. The dried sample was then subjected to a methylamidation reaction: 10 µL of solution was obtained by dissolving the sample in 4 M methylamine hydrochloride in DMSO. Then 10 µL of solution comprising 100 mM of (7-azabenzotriazol-1-yloxy)tris(pyrrolidino)phosphonium hexafluorophosphate (PyAOP) dissolved in 60% N-methylmorpholine (NMM) was added and the resulting mixture was stirred at room temperature for 1 hour (paragraphs [0141]-[0152]). The purified sample was then subjected to mass spectrometry [0147]. Nishikaze teaches that in Example 4-1 the α2,3-sialyl sugar chain was lactonized by the reaction with isopropylamine and the α2,6-sialyl sugar was isopropylamidated by the reaction with isopropylamine [0151].
Nishikaze states that the reaction time may be determined depending on the concentrations of the sample and the reagents, the reaction temperature, etc. In the method according to the present invention, modification can be performed in a shorter period of time as compared to a conventionally known method. Therefore, a sample capable of identifying the linkage type of sialic acid can be prepared even when the reaction time is about 1 hour [0063]. For example, in discussing the optimization of the methylamidation of the lactone based on altering the concentration of the methylamine, Nishikaze indicates that at a methylamine concentration of 0.08% the lactone can be completely hydrolyzed by increasing the reaction time, but that from the viewpoint of efficiency, it can be said that the concentration of the amine during lactone ring opening is preferably 0.1 % or more [0160].
The teachings of Nishikaze differ from that of the instantly claimed invention in that Nishikaze does not teach the method for preparing an analysis sample wherein the amidation reaction solution does not contain a dehydration-condensation agent to be reacted with the lactone.
Lageveen-Kammeijer discloses a method for the highly sensitive characterization of released N-glycans combining a capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) approach with linkage-specific derivatization of sialic acids and uniform cationic reducing end labelling of all glycans (abstract). Lageveen-Kammeijer teaches that majority of methods for sialic acid linkage-specific derivatization of glycans are based on the lactonization of α2,3-linked sialic acids, but that the lactones are prone to hydrolysis during sample storage. This stability issue was previously overcome by a two-step approach in which, during the second step, the lactones are hydrolyzed and stably amidated. Lageveen-Kammeijer teaches a method similar to, but an improvement on, the known two-step approach in which the lactones are hydrolyzed and then stably amidated. Lageveen-Kammeijer teaches that in this reaction, the lactonized α2,3-sialyl sugar chain that was formed by a dehydration reaction is then reacted with ammonium hydroxide to directly open the lactone ring and form a stable amide (Figure 1.b, reproduced in part below).
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Lageveen-Kammeijer teaches that this method is simpler than previous approaches as it relies on a one-pot reaction and comes with a HILIC-SPE clean-up step to remove excess reagents (page 2, paragraph 4). The reaction shows excellent linkage specificity (page 2, paragraph 4). The reaction comprises an amidation solution containing ammonium hydroxide (figure 1 and page 4 paragraph 2).
Lageveen-Kammeijer does not expressly disclose the pH of the reaction mixture in the amidation step. However, Lageveen-Kammeijer discloses a sialic acid linkage specific derivatization, in which 8 µL of 28% NH4OH solution was added to 10 µL of solution containing glycans. The resulting 18 µL reaction mixture thus has 12% NH4OH (page 4 paragraph 2). The CCI safety data sheet for ammonium hydroxide indicates that a 12% solution has a pH of greater than 11 (Section 9 - Physical Properties, found on page 4). Thus the reaction of Nishikaze would have a pH of approximately greater than 11 and thus has a pH of 7.7 or more as required by instant claim 1. The ammonia of Lageveen-Kammeijer is interpreted as satisfying both the limitation of a first compound and the limitation of an alkalizing agent in instant claim 1.
One of ordinary skill in the art would have been motivated to modify the method for preparing an analysis sample taught by Nishikaze by using the amidation reaction step of Lageveen-Kammeijer because Lageveen-Kammeijer teaches an amidation step that is simpler as it relies on a one-pot reaction and comes with a single clean-up step to remove excess reagents. One of ordinary skill in the art would have a reasonable expectation of success because the amidation step of Lageveen-Kammeijer is taught as being useful for preparing glycans for mass spectrometry analysis and showing excellent linkage specificity for different sialic acids.
Regarding the limitation “wherein the amine includes hydrazine, hydrazine derivatives, and hydroxylamine, and does not include ammonia or salts of ammonia”, this limits only the scope of the alkalinizing agent when the alkalinizing agent is an amine. The scope of the alkalinizing agent includes ammonia and salts of ammonia, and thus the combined teaching of Nishikaze and Lageveen-Kammeijer regarding ammonium hydroxide renders obvious the instant claims.
Regarding instant claim 2, the alkaline buffer solution is included as a member in the Markush describing the alkalinizing agent. The third paragraph of instant claim 2 further limits the nature of the alkaline buffer solution in the Markush but the claim does not require the alkaline buffer solution to be present. Thus the limitations of claim 2 are met by a method wherein the alkalinizing agent is any of the compounds in the Markush of instant claim 2, such as a tertiary amine.
Regarding instant claims 7 and 21, it would have been prima facie obvious to optimize the reaction time because Nishikaze teaches that reaction time may be optimized beginning with a reaction time of about 1 hour and teaches that an efficient reaction would have a shorter reaction time, which can be accomplished by increasing the concentration of the reagents, reaction temperature, etc. Nishikaze teaches that reaction time is a result effective variable such that one of ordinary skill in the art would be motivated to optimize the reaction to achieve both reaction completion and efficiency.
Regarding instant claims 18-19, as discussed above, Lageveen-Kammeijer discloses addition of a 28% NH4OH solution. The Lab-Chem safety data sheet for ammonium hydroxide indicates that a 28% solution has a pH of greater than 11.7 (Section 9.1 - Physical and Chemical Properties, found on page 5). Thus Lageveen-Kammeijer teaches the composition of instant claims 18-19.
Regarding instant claim 20, it would have been prima facie obvious to combine the teachings of Nishikaze and Lageveen-Kammeijer before the effective filing date of the claimed invention by modifying the second step of Nishikaze to be a one-pot reaction in which the lactone ring is directly opened by amidation to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the known two step methyl- or ethylamidation reaction of Nishikaze to directly open the lactone ring and form a stable amide because it is prima facie obvious to use a known technique to improve similar methods in the same way and Lageveen-Kammeijer teaches that this method similar to, but an improvement on, the known two-step approach. One of ordinary skill in the art would have been motivated to make this modification Lageveen-Kammeijer teaches that this method is simpler than previous approaches.
Response to Arguments
Applicant's arguments filed 10/17/2025 have been fully considered but they are not persuasive.
Insofar as Applicant’s arguments are applicable to the current rejections, Applicant argues that no motivation exists in Nishikaze to routinely optimize to less than 1 minute to suppress lactone degradation as required by newly added claim 21 (Remarks, page 11, paragraph 4). This is not persuasive.
Examiner notes that the feature of “to suppress lactone degradation” is not recited in rejected claim 21. Claim 21 does not require any specific level of lactone degradation or suppression of lactone degradation. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
As discussed in the above grounds of rejection, Nishikaze does provide motivation for optimizing reaction time because Nishikaze teaches that reaction time is a result effective variable such that one of ordinary skill in the art would be motivated to optimize the reaction to achieve both reaction completion and efficiency. Thus the teachings of Nishikaze in view of Lageveen-Kammeijer render obvious the instant claims.
Because Applicant’s arguments are not persuasive, the instant claims are rejected for the reasons of record with modifications made to account for the claim amendments filed 10/17/2025.
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 1-3, 7-10, and 12-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,105,717 in view of Nishikaze (US 2018/0059094 A1; IDS 06/13/2022). Although the claims at issue are not identical because the claims of ‘717 encompass a larger sequence of reactions, they are not patentably distinct from each other.
Claim 1 of ‘717 is drawn to a method for preparing an analytical sample for analysis of a glycan that includes a lactone structure and is contained in a sample, the method comprising performing a first amidation reaction that amidates a sialic acid including the lactone structure through addition of a first amidation reaction solution to the sample, the first amidation reaction solution containing ammonia an amine, or a salt thereof as a first nucleophilic agent that is reacted with the sialic acid including the lactone structure; and performing a second reaction that modifies at least a part of sialic acids not amidated in the first amidation reaction through a method different from permethylation. Claim 2 of ‘717 further limits wherein a time during which the sample is in contact with the first amidation reaction solution in order to perform the first amidation reaction is shorter than 30 minutes. Claim 3 of ‘717 further limits wherein the first amidation reaction solution does not include a dehydration condensation agent that is reacted with the sialic acid. Claim 4 of ‘717 further limits wherein the amine is a primary amine. Claim 6 of ‘717 further limits wherein the amine includes an unbranched alkyl group. Claim 7 of ‘717 further limits wherein the pH of the first amidation reaction solution is 8.0 or higher. Claim 8 of ‘717 further limits wherein the first amidation reaction solution contains an amine or a salt thereof. Claim 10 of ‘717 further limits wherein the second reaction solution contains ammonia an amine an alcohol, or a salt thereof as a second nucleophilic agent that is reacted with a sialic acid not amidated in the first amidation reaction.
Claim 14 of ‘717 further limits wherein α2,6-sialic acid and at least one of α2,3-sialic acid α2,8-sialic acid and α2,9-sialic acid are modified into different modified products in the second reaction. Claim 16 of ‘717 further limits wherein the prepared analytical sample is analyzed through at least one of mass spectrometry and chromatography.
The claims of ‘717 do not limit wherein when or that the first compound is a carbonate salt, a hydrochloride salt, a nitrate salt, a sulfate salt, a phosphate salt, or wherein a methanesulfonate salt of at least one compound selected from ammonia, amine, hydroxylamine, hydrazine, and a hydrazine derivative (instant claim 3), or wherein a carbon number of the linear hydrocarbon group on the first compound is any one of 1 to 6 (instant claim 10).
Nishikaze discloses a method of preparing a sample for analysis of a glycoprotein or glycopeptide [0013] which comprises modification of a carboxy group of sialic acid of a sugar chain [0014]. In this modification α2,3-linked sialic acids and α2,6-linked sialic acids form derivatives having different masses, and determination of the presence or absence of sialic acid in the sugar chain of a glycoprotein or glycopeptide and identification of the linkage type of sialic acid can be simply performed by mass spectrometry with a high degree of accuracy [0023]. Example 4 of Nishikaze modifies free sugar chains released from fetuin, which has high α2,3-sialyl sugar chain content [0135]. Specifically, Nishikaze discloses Example 4-1 in which a sugar chain was modified using DIC and HOBt as a dehydration-condensation agent and isopropylamine hydrochloride as an amine hydrochloride. The sample was then purified using a GL-Tip Amide carrier and centrifugation with washing followed by a drying step. The dried sample was then subjected to a methylamidation reaction: 10 µL of solution was obtained by dissolving the sample in 4 M methylamine hydrochloride in DMSO. Then 10 µL of solution comprising 100 mM of PyAOP dissolved in 60% NMM was added and the resulting mixture was stirred at room temperature for 1 hour (paragraphs [0141]-[0152]). The purified sample was then subjected to mass spectrometry [0147].
It would have been prima facie obvious to combine the teachings of Nishikaze with the claims of ‘717 before the effective filing date of the claimed invention by selecting methylamine hydrochloride as the amine of ‘717 and including NMM to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to include methylamine hydrochloride and NMM in the method of ‘717 because Nishikaze discloses these reagents as useful to provide a method for preparing a sample comprising a glycan allowing identification of the linkage type of sialic acid by mass spectrometry with a high degree of accuracy, and ‘717 claims a method for preparing a sample comprising a glycan wherein the prepared sample is analyzed through at least one of mass spectrometry and chromatography. One of ordinary skill in the art would have a reasonable expectation of success because ‘717 claims an amine bearing an unbranched alkyl group, which includes a methyl group, and claims that the pH is 8 or higher, which suggests that the reaction solution contains a base.
Regarding instant claim 2, the alkaline buffer solution is included as a member in the Markush describing the alkalinizing agent. The third paragraph of instant claim 2 further limits the nature of the alkaline buffer solution in the Markush but the claim does not require the alkaline buffer solution to be present. Thus the limitations of claim 2 are met by a method wherein the alkalinizing agent is any of the compounds in the Markush of instant claim 2.
Regarding instant claims 18-19, ‘717 does not expressly claim a kit for preparing an analysis sample used in the method for preparing an analysis sample according to instant claim 1 or 16. However, the combined claims of ‘717 and teachings of Nishikaze suggest a reaction solution comprising NMM and methylamine hydrochloride with a pH 8 or higher. Thus the composition of instant claims 18-19 is rendered obvious.
Regarding instant claim 21, Nishikaze states that the reaction time may be determined depending on the concentrations of the sample and the reagents, the reaction temperature, etc. [0063]. It would have been prima facie obvious to optimize the reaction time because Nishikaze teaches that reaction time may be optimized and teaches that an efficient reaction would have a shorter reaction time, which can be accomplished by increasing the concentration of the reagents, reaction temperature, etc. and ‘717 claims that that the amidation is shorter than 30 minutes (claim 3). Nishikaze teaches that reaction time is a result effective variable such that one of ordinary skill in the art would be motivated to optimize the reaction to achieve both reaction completion and efficiency.
Claims 1-3, 7-10, and 12-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,971,336 in view of Nishikaze (US 2018/0059094 A1; IDS 06/13/2022). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 of ‘336 is drawn to a method for preparing a sample comprising a glycan comprising performing a lactonization reaction in which at least a part of sialic acids included in the glycan is lactonized performing an amidation reaction in which lactones of lactonized sialic acids are amidated by aminolysis based on an interaction between an amino group and a lactone through addition of an amidation reaction solution to the sample, wherein the amidation reaction solution comprises ammonia, an amine, or a salt thereof is reacted with the lactonized sialic acids, wherein the concentration of ammonia, an amine, or a salt thereof in the amidation reaction solution is 0.5 M or more, wherein: the amine is a primary amine; pH of the amidation reaction solution is 7.7 or higher; and in the lactonization reaction, at least one selected from the group consisting of α2,3-sialic acid, α2,8-sialic acid and α2,9-sialic acid among the sialic acids is lactonized, wherein an operation that reacts the sample with a dehydration condensation agent is not performed after the addition of the amidation reaction solution to the sample, wherein: the amidation reaction solution does not include a dehydration condensation agent that is reacted with the lactones, and wherein only contacting the sample with the amidation reaction solution is performed for the amidation reaction. Claim 3 of ‘336 further limits wherein a time during which the sample is in contact with the amidation reaction solution for the amidation reaction is shorter than 30 minutes. Claim 5 of ‘336 further limits that the amine includes an unbranched alkyl group. Claim 9 of ‘336 further limits wherein the lactonization reaction solution further comprises a nucleophilic agent that is reacted with the sialic acids included in the glycan; the nucleophilic agent differs in mass from the ammonia or the amine used in the amidation reaction. Claim 10 of ‘336 further limits wherein α2,3-sialic acid is lactonized and α2,6-sialic acid is linked to a part of the nucleophilic agent through addition of the lactonization reaction solution to the sample. Claim 14 of ‘336 further limits wherein the prepared sample is analyzed through at least one of mass spectrometry and chromatography. Claim 16 of ‘336 further limits wherein the lactone rings of the lactonized sialic acids are opened by aminolysis, and do not require hydrolysis.
The claims of ‘336 do not limit wherein the first compound is a carbonate salt, a hydrochloride salt, a nitrate salt, a sulfate salt, a phosphate salt, or a methanesulfonate salt of at least one compound selected from ammonia, amine, hydroxylamine, hydrazine, and a hydrazine derivative (instant claim 3), or that wherein a carbon number of the linear hydrocarbon group on the first compound is any one of 1 to 6 (instant claim 10).
Nishikaze discloses a method of preparing a sample for analysis of a glycoprotein or glycopeptide [0013] which comprises modification of a carboxy group of sialic acid of a sugar chain [0014]. In this modification α2,3-linked sialic acids and α2,6-linked sialic acids form derivatives having different masses, and determination of the presence or absence of sialic acid in the sugar chain of a glycoprotein or glycopeptide and identification of the linkage type of sialic acid can be simply performed by mass spectrometry with a high degree of accuracy [0023]. Example 4 of Nishikaze modifies free sugar chains released from fetuin, which has high α2,3-sialyl sugar chain content [0135]. Specifically, Nishikaze discloses Example 4-1 in which a sugar chain was modified using DIC and HOBt as a dehydration-condensation agent and isopropylamine hydrochloride as an amine hydrochloride. The sample was then purified using a GL-Tip Amide carrier and centrifugation with washing followed by a drying step. The dried sample was then subjected to a methylamidation reaction: 10 µL of solution was obtained by dissolving the sample in 4 M methylamine hydrochloride in DMSO. Then 10 µL of solution comprising 100 mM of PyAOP dissolved in 60% NMM was added and the resulting mixture was stirred at room temperature for 1 hour (paragraphs [0141]-[0152]). The purified sample was then subjected to mass spectrometry [0147].
It would have been prima facie obvious to combine the teachings of Nishikaze with the claims of ‘336 before the effective filing date of the claimed invention by selecting methylamine hydrochloride as the amine of ‘336 and including NMM to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to include methylamine hydrochloride and NMM in the method of ‘336 because Nishikaze discloses these reagents as useful to provide a method for preparing a sample comprising a glycan allowing identification of the linkage type of sialic acid by mass spectrometry with a high degree of accuracy, and ‘336 claims a method for preparing a sample comprising a glycan wherein the prepared sample is analyzed through at least one of mass spectrometry and chromatography. One of ordinary skill in the art would have a reasonable expectation of success because ‘336 claims an amine bearing an unbranched alkyl group, which includes a methyl group, and claims that the pH is 7.7 or higher, which suggests that the reaction solution contains a base.
Regarding instant claim 2, the alkaline buffer solution is included as a member in the Markush describing the alkalinizing agent. The third paragraph of instant claim 2 further limits the nature of the alkaline buffer solution in the Markush but the claim does not require the alkaline buffer solution to be present. Thus the limitations of claim 2 are met by a method wherein the alkalinizing agent is any of the compounds in the Markush of instant claim 2.
Regarding instant claims 18-19, ‘336 does not expressly claim a kit for preparing an analysis sample used in the method for preparing an analysis sample according to instant claim 1 or 16. However, the combined claims of ‘336 and teachings of Nishikaze suggest a reaction solution comprising NMM and methylamine hydrochloride with a pH of greater than 7.7. Thus the composition of instant claims 18-19 is rendered obvious.
Regarding instant claim 21, Nishikaze states that the reaction time may be determined depending on the concentrations of the sample and the reagents, the reaction temperature, etc. [0063]. It would have been prima facie obvious to optimize the reaction time because Nishikaze teaches that reaction time may be optimized and teaches that an efficient reaction would have a shorter reaction time, which can be accomplished by increasing the concentration of the reagents, reaction temperature, etc. and ‘336 claims that that the amidation is shorter than 30 minutes (claim 3). Nishikaze teaches that reaction time is a result effective variable such that one of ordinary skill in the art would be motivated to optimize the reaction to achieve both reaction completion and efficiency.
Claims 1-3, 7-10, and 12-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,110,309 in view of Nishikaze (US 2018/0059094 A1; IDS 06/13/2022). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 of ‘309 is drawn to a method for preparing an analytical sample for analysis of a glycan contained in a sample, the method comprising: performing an amidation reaction that amidates a lactone structure included in the glycan through contacting the sample with a reaction solution that has a pH of higher than 10; adding an acidic solution to the reaction solution after the amidation reaction; and purifying the sample contained in the reaction solution by using a carrier for hydrophilic interaction chromatography after the acidic solution is added to the reaction solution, wherein: the amidation reaction amidates the lactone structure included in the glycan by aminolysis based on an interaction between an amino group and a lactone; the reaction solution comprising at least one selected from the group consisting of ammonia, a primary amine, and a salt thereof; wherein the concentration of ammonia, a primary amine, or a salt thereof in the reaction solution is 0.5 M or more; a time during which the sample is in contact with the reaction solution for the amidation reaction is shorter than 30 minutes; performing a lactonization reaction that lactonizes at least a part of sialic acids included in the glycans before the amidation reaction, wherein in the lactonization reaction, at least one selected from the group consisting of α2,3-sialic acid, α2,8-sialic acid, and α2,9-sialic acid among the sialic acids is lactonized an operation that reacts the sample with a dehydration condensation agent is not performed after the addition of the reaction solution to the sample, wherein: the reaction solution does not include a dehydration condensation agent that is reacted with the lactones, and wherein only contacting the sample with the amidation reaction solution is performed for the amidation reaction. Claim 4 of ‘309 further limits wherein the reaction solution to be used for the amidation reaction contains ammonia or an amine, the lactonization reaction solution further contains a nucleophilic agent that is reacted with a sialic acid included in the glycan, the nucleophilic agent is different from ammonia or the amine contained in the reaction solution to be used for the amidation reaction, and in the lactonization reaction, a part of the sialic acids is lactonized based on a linkage type of the sialic acid, and at least a part of the nucleophilic agent is linked to another part of the sialic acids through addition of the lactonization reaction solution to the sample. Claim 8 of ‘309 further limits wherein α2,3-sialic acid is lactonized and a part of the nucleophilic agent is linked to α2,6-sialic acid through addition of the lactonization reaction solution to the sample in the lactonization reaction. Claim 11 of ‘309 further limits wherein the prepared analytical sample is analyzed through at least one of mass spectrometry and chromatography. Claims 13 and 14 of ‘309 further limit wherein the amidation reaction amidates the lactone structure included in the glycan by aminolysis and the reaction solution comprising at least one selected from the group consisting of ammonia, an amine, and a salt thereof and the amine is a primary amine.
The claims of ‘309 do not limit that the first compound is a carbonate salt, a hydrochloride salt, a nitrate salt, a sulfate salt, a phosphate salt, or wherein a methanesulfonate salt of at least one compound selected from ammonia, amine, hydroxylamine, hydrazine, and a hydrazine derivative (instant claim 3), or wherein a carbon number of the linear hydrocarbon group on the first compound is any one of 1 to 6 (instant claim 10).
Nishikaze discloses a method of preparing a sample for analysis of a glycoprotein or glycopeptide [0013] which comprises modification of a carboxy group of sialic acid of a sugar chain [0014]. In this modification α2,3-linked sialic acids and α2,6-linked sialic acids form derivatives having different masses, and determination of the presence or absence of sialic acid in the sugar chain of a glycoprotein or glycopeptide and identification of the linkage type of sialic acid can be simply performed by mass spectrometry with a high degree of accuracy [0023]. Example 4 of Nishikaze modifies free sugar chains released from fetuin, which has high α2,3-sialyl sugar chain content [0135]. Specifically, Nishikaze discloses Example 4-1 in which a sugar chain was modified using DIC and HOBt as a dehydration-condensation agent and isopropylamine hydrochloride as an amine hydrochloride. The sample was then purified using a GL-Tip Amide carrier and centrifugation with washing followed by a drying step. The dried sample was then subjected to a methylamidation reaction: 10 µL of solution was obtained by dissolving the sample in 4 M methylamine hydrochloride in DMSO. Then 10 µL of solution comprising 100 mM of PyAOP dissolved in 60% NMM was added and the resulting mixture was stirred at room temperature for 1 hour (paragraphs [0141]-[0152]). The purified sample was then subjected to mass spectrometry [0147].
It would have been prima facie obvious to combine the teachings of Nishikaze with the claims of ‘309 before the effective filing date of the claimed invention by selecting methylamine hydrochloride as the amine of ‘309 and including NMM to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to include methylamine hydrochloride and NMM in the method of ‘309 because Nishikaze discloses these reagents as useful to provide a method for preparing a sample comprising a glycan allowing identification of the linkage type of sialic acid by mass spectrometry with a high degree of accuracy, and ‘309 claims a method for preparing a sample comprising a glycan wherein the prepared sample is analyzed through at least one of mass spectrometry and chromatography. One of ordinary skill in the art would have a reasonable expectation of success because ‘309 claims an amine bearing an unbranched alkyl group, which includes a methyl group, and claims that the pH is 8 or higher, which suggests that the reaction solution contains a base.
Regarding instant claim 2, the alkaline buffer solution is included as a member in the Markush describing the alkalinizing agent. The third paragraph of instant claim 2 further limits the nature of the alkaline buffer solution in the Markush but the claim does not require the alkaline buffer solution to be present. Thus the limitations of claim 2 are met by a method wherein the alkalinizing agent is any of the compounds in the Markush of instant claim 2.
Regarding instant claims 18-19, ‘309 does not expressly claim a kit for preparing an analysis sample used in the method for preparing an analysis sample according to instant claim 1 or 16. However, the combined claims of ‘309 and teachings of Nishikaze suggest a reaction solution comprising NMM and methylamine hydrochloride with a pH of greater than 10. Thus the composition of instant claims 18-19 is rendered obvious.
Regarding instant claim 21, Nishikaze states that the reaction time may be determined depending on the concentrations of the sample and the reagents, the reaction temperature, etc. [0063]. It would have been prima facie obvious to optimize the reaction time because Nishikaze teaches that reaction time may be optimized and teaches that an efficient reaction would have a shorter reaction time, which can be accomplished by increasing the concentration of the reagents, reaction temperature, etc. and ‘309 claims that that the amidation is shorter than 30 minutes (claim 1). Nishikaze teaches that reaction time is a result effective variable such that one of ordinary skill in the art would be motivated to optimize the reaction to achieve both reaction completion and efficiency.
Response to Arguments
Applicant's remarks filed 10/17/2025 have been fully considered but they are not persuasive. Applicant states that none of the claims of the reference patents cited by the Office, including in view of Nishikaze and Lageveen-Kammeijer, are patentably indistinct from the claims of the present application. However, Applicant does not provide any argument as to why this is the case. Because Applicant’s arguments are not persuasive, the instant claims are rejected for the reasons of record with modifications made to account for the claim amendments filed 10/17/2025.
Conclusion
No claims are allowed.
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 extension fee 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 date of this final action.
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/S.G.H./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693