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 .
Priority
This application was filed on and is a U.S. national Stage application under 35 U.S.C. 371 of International Patent Application No. 371 of PCT/CN2022/100188 filed 06/21/2022, which claims the benefit of the priority of China Patent Application No. 202111076889.8 filed 09/14/2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement submitted on 06/12/2026 has been considered by the examiner.
Claim Status
Claims 1, 7-8, 10, 14-18 are pending. Claims 16-18 are new. Claims 1, 7-8, 10, 14 are amended. Claims 2-6, 9, 11-13 are canceled. Claims 1, 7-8, 10, 14-18 are being examined on the merits in this office action.
Drawings - Withdrawn
The objection to the drawings is withdrawn in view of the amended drawings.
Claim Rejections - Withdrawn
The rejection of claims 14-15 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn in view of the claim amendments.
The rejection of claims 4-5 and 12-13 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn because the claims are canceled.
Claim Rejections - 35 USC § 103 – Maintained and Updated
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 7-8, 10, 14-15, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Jasprica et al. (US20180133286A1 – hereinafter “Jasprica”) in view of Duan et al. (CN105288591A – hereinafter “Duan”) and Sigma Aldrich (N-Methyl-DL-alanine 600-21-5 - Jun, 7, 2021).
Jasprica teaches an aqueous pharmaceutical composition that comprises vancomycin and an amino acid or amino acid derivative such as N-acetyl-Glycine or N-acetyl-D-Alanine and that the amino acids or amino acid derivatives such as N-acetyl-Glycine or N-acetyl-D-Alanine are used to stabilize the composition (Abstract; claims 1; [0020-0025, 0037-0039], and that the composition comprises water [0036, 0078-0079, 0081, 0112, 0239]. Jasprica teaches an aqueous pharmaceutical composition comprising about 0.5-15% vancomycin and N-acetyl-D-Alanine (claims 11, 14; [0041, 0100, 0112), and that the ratio of modified alanine such as N-acetyl-D-Alanine to vancomycin and is about 5:1 to 40:1 [0103]. Jasprica also teaches that the composition comprises 3-10% or 1-10% Alanine derivative N-acetyl-D-Alanine [0047-0049]. Even though Jasprica teaches the addition of an alanine derivative, the reference does not teach the addition of N-methylalanine. However, it is known in the art to add N-methylalanine in compositions to stabilize the composition as taught by Duan and Sigma Aldrich.
Duan teaches a pharmaceutical composition that comprises the addition of N-methylalanine and teaches that the addition of N-methylalanine improves the stability of the pharmaceutical composition and enhances the efficacy of the drug [0010-0014].
Additionally, Sigma Aldrich teaches N-Methyl-DL-alanine for use in drug design and development (Page 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Jasprica and use other Alanine derivatives such as N-methylalanine since Duan teaches that N-methyl alanine is added for stabilizing compositions. Additionally, Jasprica teaches that the Alanine derivatives that were added were also effective in stabilizing the composition. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in using other types of Alanine derivatives in the composition since Sigma Aldrich teaches N-Methyl-DL-alanine is used for drug design and Duan teaches that addition of N-methylalanine in peptide drugs stabilized the drug composition (Abstract; claims 1; [0020-0025, 0037-0039]). The disclosures render obvious claim 1.
Regarding claims 7-8, Jasprica teaches that the composition comprising vancomycin, Alanine derivative and water has a pH of 4-6 [0028-0031, 0041-0056] and that the pH is adjusted by addition of aqueous hydrochloric acid solutions or aqueous sodium hydroxide solutions [0077].
Regarding claim 10, Jasprica teaches that the pH of the composition comprising vancomycin, Alanine derivative and water can be adjusted by 0.01 M HCl, 0.1 M HCl, 1 M HCl, 2 M HCl, 3 M HCl, 4 M HCl, 5 M HCl, 6 M HCl, 0.01 M NaOH, 0.1 M NaOH, 1 M NaOH, 2 M NaOH, 3 M NaOH, 4 M NaOH, 5 M NaOH and 6 M NaOH. Thus, suitable pH adjusting agents include, but are not limited to 0.01-6 M HCl and 0.01-6 M NaOH [0077, 0211, 0236].
Regarding claims 14-15, Jasprica teaches a method of treating bacterial infections in a subject in need thereof, comprising administering an aqueous pharmaceutical composition (claim 22; [0096). Examiner notes that the aqueous pharmaceutical composition is rendered obvious as shown above. Jasprica further teaches that the composition has activity against Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 and Streptococcus pnemoniae ATCC 49619 [0241]. Jasprica teaches that vancomycin is used for treatment of serious or severe infections caused by susceptible strains of methicillin-resistant (beta-lactam-resistant) staphylococci [0004].
Regarding claim 18, Jasprica teaches an aqueous pharmaceutical composition that comprises vancomycin and an amino acid or amino acid derivative such as N-acetyl-Glycine or N-acetyl-D-Alanine and that the amino acids or amino acid derivatives such as N-acetyl-Glycine or N-acetyl-D-Alanine are used to stabilize the composition (Abstract; claims 1; [0020-0025, 0037-0039], and that the composition comprises water [0036, 0078-0079, 0081, 0112, 0239]. Jasprica teaches an aqueous pharmaceutical composition comprising about 0.5-15% vancomycin and N-acetyl-D-Alanine (claims 11, 14; [0041, 0100, 0112), and that another amino acid that can be added is L-Lysine hydrochloride [0110]. Jasprica also teaches that the composition comprises 3-10% or 1-10% Alanine derivative N-acetyl-D-Alanine [0047-0049]. Jasprica teaches that the composition comprises 50% V/V or less PEG 400 [0079], and water q.s [0112] and that the composition for injection [0222].
Claim Rejections - 35 USC § 103 – New
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Jasprica et al. (US20180133286A1 – hereinafter “Jasprica”) in view of Duan et al. (CN105288591A – hereinafter “Duan”) and Sigma Aldrich (N-Methyl-DL-alanine 600-21-5 - Jun, 7, 2021) as applied to claim 1 above, and further in view of Rigas (US20190343848A1 – hereinafter “Rigas”).
The teachings of Jasprica, Duan and Sigma are disclosed above and incorporated herein by reference.
Jasprica does not teach that the composition comprising vancomycin comprises gelatin or benzalkonium chloride as recited in claims 16-17.
Rigas teaches a composition that comprises vancomycin [0033, 0165], and that the composition for use as eye drops [0140, 0142, 0148-0149], also comprises excipients in the amount of 0.1 to 0.8% [0335], such as gelatin [0319], and that the composition further comprises preservatives in the amount of 0.001% to about 0.1% [0328], such as benzalkonium chloride [0264] and also includes water [0257, 0265, 0316].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of Jasprica and include gelatin to form a gel or include benzalkonium chloride for an eye drop since Rigas successfully teaches a composition that similarly comprises vancomycin and comprises gelatin as a gel composition or comprises benzalkonium chloride for use as an eye drop. One of ordinary skill in the art would have had a reasonable expectation of success in including the excipients and preservatives as taught by Rigas, since the excipients are known to be added in compositions comprising vancomycin for use as eye drops or as vancomycin gels. The disclosures render obvious claims 16-17.
Response to Arguments
Applicant's arguments filed 08/11/2026 have been fully considered but they are not persuasive.
Applicant Arguments
Applicant argues that the instant composition comprising vancomycin and N-methyl-D-alanine achieves the effects of improving stability of vancomycin and inhibit impurity formation (Page 6-8 of arguments).
Applicant argues that Jasprica does not teach N-methyl-D-alanine and does not teach using other N-substitute alanine can achieve significantly improved stabilization against vancomycin degradation (Page 8-10 of arguments).
Applicant argues that Duan does not teach composition of vancomycin (Page 11 of Arguments). Applicant further argues that Sigma is a general teaching and does not teach N-methyl-D-alanine in a composition with vancomycin (Page 11-12 of Arguments).
Examiner’s Response
The arguments presented above have been fully considered but are unpersuasive. Examiner notes that a composition comprising vancomycin and the addition of an alanine derivative is known in the art as taught by Jasprica. Examiner acknowledges that Jasprica does not teach the addition of the alanine derivative N-Methyl-D-alanine. However, this alanine derivative is known in the art and is known to be added in compositions as taught by Duan. One of ordinary skill in the art would be motivated to add N-Methyl-alanine in pharmaceutical compositions since Duan teaches that N-Methyl-alanine is known to improve the stability of pharmaceutical composition. Thus, this is an expected result of the addition of an alanine derivative in a composition comprising vancomycin. Additionally, Examiner’s adds that it is known in the are that vancomycin is known to have limited stability, thus one of ordinary skill in the art would be motivated to add an alanine derivative such as N-Methyl-alanine to stabilize vancomycin and reduce impurity.
Regarding Applicant argument that Duan does not teach composition of vancomycin or that Jasprica does not teach N-methyl-D-alanine, Examiner reminds Applicant that the obviousness rejection based on the combined teachings of Jasprica, Duan and Sigma. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The addition of an alanine derivative in a composition comprising vancomycin is known in the art as taught by Jasprica. Additionally, Jasprica teaches that the addition of the alanine derivative is to stabilize vancomycin. Additionally, Duan teaches the specific instant alanine derivative and teaches that the alanine derivative is added to stabilize pharmaceutical compositions. One of ordinary skill in the art is aware from the teachings of Jasprica, that the addition of an alanine derivative is important to stabilize vancomycin and thus would be motivated to add other forms of alanine derivatives such as the one taught by Duan since, Duan similarly teaches that the specific derivative is known to stabilize pharmaceutical compositions. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). The arguments are unpersuasive.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MERCY H SABILA/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
