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 statements submitted on 03/12/2024, and 10/14/2025 have been considered by the examiner.
Claim Status
Claims 1-15 are being examined on the merits in this office action.
Drawings
The drawings are objected to because the description of the Y and X axis is not clear in Fig. 1-5. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claim Interpretation
Claim 14 recites “A method for treating and preventing bacterial infections including a staphylococcal infection…”.
Examiner is interpretating the claim as open ended, that the method treats all bacterial infections including staphylococcal infections etc.
Claims 14-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating bacterial infections caused by methicillin-resistant staphylococcus aureus (MRSA), and methicillin-resistant coagulase-negative staphylococcus or penicillin-resistant streptococcus pneumoniae (PRSP), does not reasonably provide enablement for a method of treating and preventing all bacterial infections including gram negative bacteria. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. This is a scope of enablement rejection.
To be enabling, the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1561 (Fed. Cir., 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558,1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547, the court recited eight factors to consider when assessing whether or not a disclosure would require undue experimentation. These factors are:
1) the quantity of experimentation necessary
2) the amount of direction or guidance provided
3) the presence or absence of working examples
4) the nature of the invention
5) the state of the art
6) the relative skill of those in the art
7) the predictability of the art
8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099,1108,427 F.2d 833, 839,166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The breadth of the claims and the nature of the invention
The invention is drawn to a method for treating and preventing bacterial infections including a staphylococcal infection and Streptococcus pneumoniae, comprising administering the pharmaceutical composition comprising vancomycin.
Examiner notes that vancomycin is known in the art as one of only a few antibiotics available to treat patients infected with methicillin resistant Staphylococcus aureus and methicillin resistant, coagulase-negative Staphylococcus species and is thus a valuable antimicrobial in treating Gram-positive bacterial infections (Rao et al. IJPRA 9:1, 1218-1223, 2024). Rao teaches that there is an increasing emergence of vancomycin resistant enterococci leading to guidelines restricting the use of vancomycin (Page 1219).
Secondly, the term “preventing” is a potent and absolute term indicating that the method of prevention will necessarily prevent the onset of any cancer, regardless of the cause and in every instance by the administration of vancomycin.
Since the instant specification does not provide a limiting definition of the term “preventing”, the term has been interpreted expansively. The term “preventing” encompasses a wide range of situations, from preventing any bacterial infection from occurring to preventing it from progressing, and in addition, the term is not limited by any time frame.
The applicant is claiming a “method of preventing” in claim 14. Prevention, as defined by Merriam-Webster dictionary, is to keep from happening or existing, which implies taking advance measure against something possible or probable. In addition, preventing embraces complete 100% inhibition. Therefore, the evidence of 100% prevention would be more challenging to obtain than the evidence of treatment since one would have to show that the administration of vancomycin, one would never develop any bacterial infection. The instant specification is bereft of evidence of prevention of any or all bacterial infections.
The specification does not demonstrate the efficacy of vancomycin in treating and preventing all bacterial infections including gram negative bacterial infections.
The claims are thus broad insofar as to suggest that the claimed composition can treat and prevent all bacterial infections.
The state of the prior art and the level of predictability in the art and the relative skill of those in the art
The state of the art is such that there is evidence and established literature on vancomycin and that it is known in the art as one of only a few antibiotics available to treat patients infected with methicillin resistant Staphylococcus aureus and methicillin resistant, coagulase-negative Staphylococcus species and is thus a valuable antimicrobial in treating Gram-positive bacterial infections (Rao et al. IJPRA 9:1, 1218-1223, 2024). Rao teaches that there is an increasing emergence of vancomycin resistant enterococci leading to guidelines restricting the use of vancomycin (Page 1219).
Additionally, it is known that vancomycin is not effective for treatment of infections caused by gram-negative bacteria (Rolston et al.). Additionally, Rolston teaches that among the Enterococcus species, resistance to vancomycin is now ≥ 30% and that gram-positive organisms intrinsically resistant to vancomycin (e.g., Leuco-nostoc species, Lactobacillus species, and Pediococcus species) (Page 247).
Given that there is no evidence in the art of the effect of vancomycin in treating all bacteria including gram-negative bacteria, the treatment and prevention of all bacterial infection with vancomycin is not considered enabled.
One of ordinary skill in the art would not be able to use the claimed invention to treat and prevent all bacterial infections including VRE. It is well established that a utility rejection is therefore proper when the scope of enablement is not reasonably correlated to the scope of the claim.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)”. The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.”
The instant disclosure is focused on the HPLC profile of the different composition in different conditions (Fig. 1-5). As a result, the specification needs to have more details on the effect of vancomycin in treating bacterial infections including gram negative bacteria.
The relative skill of those in the art is high. However, the art of treating and preventing all bacterial infections using vancomycin is unpredictable. In light of the state of the prior art, it is apparent that vancomycin is not capable of use to treat and prevent all bacterial infections.
The amount of direction or guidance provided and the presence or absence of working examples
The claims are drawn to a method for treating and preventing bacterial infections including a staphylococcal infection and Streptococcus pneumoniae, comprising administering the pharmaceutical composition comprising vancomycin. The instant disclosure is focused on the HPLC profile of the different composition in different conditions (Fig. 1-5).
The instant specification does not include other examples showing effect of vancomycin on treating and preventing bacterial infections including VRE or gram-negative bacteria.
The quantity of experimentation necessary
Given the well-known unpredictability of the art as well the incomplete experimental evidence commensurate in scope with the claims, the skilled artisan would not be able to agree that vancomycin is not capable of use to treat and prevent all bacterial infections. In order to determine if the claimed method will treat bacterial infections including gram-negative bacteria or VRE, the suitable dosage as well as clinical trials or assays that can correlate to clinical efficacy of such treatment would be needed. This is undue experimentation given the limited guidance and experimentation provided by the applicant.
In view of the Wands factors discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in unduly burdensome experimentation to assess whether administration of vancomycin would be successful in treating and preventing all bacterial infections. Thus, the rejection of these claims under 35 USC 112(a) is proper.
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 4-5 and 12-13 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 4 recites the limitation "….wherein the concentration of the N-methyl-D-alanine is 0.1-30% w/w " in line 1-2. Examiner notes that claim 4 depends on claim 1 and claim 1 recites N-methylalanine generally (a genus) and not specifically N-methyl-D-alanine. Therefore, there is insufficient antecedent basis for this limitation in the claim. Claim 5 has a similar issue.
Claim 12 depends on claim 1 and recites “…N-methyl-amino acid…”. Examiner notes that claim 1 recites “N-methylalanine” and not any amino acid as recited in claim 12. Therefore, there is insufficient antecedent basis for this limitation in the claim. Claim 13 has a similar issue.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-15 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].
Even though Jasprica teaches the addition of an alanine derivative, but 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 disclosure render obvious claim 1.
Regarding claims 2-5, Jasprica teaches that the composition comprises 3-10% or 1-10% Alanine derivative N-acetyl-D-Alanine [0047-0049]. It would have been obvious to use another Alanine derivative such as N-methylalanine as taught by Sigma Aldrich and Duan at concentration taught by Jasprica.
Regarding claim 6, 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-Methyl-DL-alanine for stability of pharmaceutical composition.
Regarding claims 7-8, Jasprica teaches that the composition comprising vancomycin, Alanine derivative and water has a pH of 4-6 [0041-0056].
Regarding claims 9-10, 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 claim 11, Sigma Aldrich teaches N-Methyl-DL-alanine for use in drug design and development (Page 3). It would have been obvious to use another Alanine derivative such as N-methylalanine as taught by Sigma Aldrich and Duan at the recited concentration of Jasprica.
Regarding claims 12-13, Jasprica teaches that the molar ratio of N-acetyl-D-Alanine to vancomycin is about 0.1:1 to 40:1 or 5:1 to 40:1 (claims 5-6). It would have been obvious to use another Alanine derivative such as N-methylalanine as taught by Sigma Aldrich and Duan at the ratios taught by Jasprica.
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].
Conclusion
No claims are allowed.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MERCY H SABILA/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
Prosecution Insights