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 .
Claim Status
Claims 1-20 are pending. Claim 5 was amended, and claims 6-20 were added in the Reply filed 7/29/2026. Claims 1-4 and 17-20 are withdrawn. Claims 5-16 are presently considered.
Election/Restrictions
Applicant’s election without traverse of Group II (method of claim 5) and the originally elected species of “aCys_H_H_H”, characterized in part by a container having a headspace comprising 21.0% O2, in the reply filed on 3/04/2026 was previously acknowledged.
However, Applicant did not identify if the added or amended claims read upon the originally elected species1, and claim 1 is now amended to recite and require a new limitation.
In the Reply filed 7/29/2026, previously examined claim 5 was amended to recite and require “an air-containing gas”, which is a novel phrase not previously utilized on record. Critically, neither the phrase “an air-containing gas” nor “air” is defined in the originally filed disclosure. Rather “air” is used once in the specification to refer to “a suitable container with air as headspace”2. Therefore, “an air-containing gas” can only mean “air” consistent with the originally filed disclosure.
However, “air” is utilized in the art to refer to a gas comprising “approximately 78% nitrogen, approximately 20% oxygen, and approximately 1% argon plus minor amounts of other gases” (see, e.g., US20180256717 at ¶[0254]), wherein “ambient air at sea level” includes “20.9% oxygen” (see, e.g., US20170239289 A1 at ¶[0296]), and wherein the figure of 20.9% O2 refers to “dry” air, but this percentage is actually lower (e.g., 18.6%) if gaseous water is present3.
This is pertinent because the originally elected species required 21.0% O2 (three significant digits), but “air” contains 20.9% or less O2 (three significant digits), wherein “wet” air contains less than 20.9% O24. Accordingly, amended claim 1 as filed 7/29/2026 is understood to now exclude the originally elected species because the claim now requires 20.9% O2 (or less, depending upon the amount of gaseous H2O).
Accordingly, per MPEP § 803.02(III),
Should applicant, in response to a rejection of a Markush claim, overcome the rejection by amending the Markush claim to exclude the species anticipated or rendered obvious by the prior art, the amended Markush claim will be examined again. The examination will be extended to the extent necessary to determine patentability of the Markush claim. In the event prior art is found during this examination that anticipates or renders obvious the amended Markush claim, the claim will be rejected and the action can be made final…
Here, “the Markush claim” is instant claim 5. Accordingly, because the Markush claim was amended to exclude the originally elected species as well as the previously examined non-elected species, examination has been extended to the extent necessary to determine patentability of the Markush claim.
Examination has now proceeded to the subgenus of non-elected species of methods of claim 5, wherein 0.5 % w/V of vancomycin is added to N-acetyl-D-Cys (NAC) at a molar ratio of about 1:1-1:30, wherein the pH is adjusted to about 3.0 to 6.0 using HCl or NaOH, and wherein the resulting composition is packaged in a container having a headspace of sterile atmospheric air with an oxygen content of approximately 17.9% atm up to 20.9 % atm.
Following extensive search and examination, these non-elected species have been deemed obvious in view of the prior art, which is applied below. Per MPEP § 803.02(III), claims to other non-elected species are held withdrawn, and the prior art search has not been extended unnecessarily to cover all nonelected species, but only to the extent necessary to determine patentability of the Markush claim of claim 5.
The non-elected species is understood to read upon instant claims 5-16, but not to read upon instant claims 17-20.
Claims 1-4 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/04/2026.
Claims 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/04/2026.
Claims 5-16 are presently considered.
Priority
The priority claim to EP20214654.4 (filed 12/16/2020) is acknowledged.
Information Disclosure Statement
No IDS was submitted in the Reply filed 7/29/2026.
It is noted that the duty of disclosure, candor, and good faith is applicable to named inventors, each attorney or agent that prepares or prosecutes, and all persons substantively involved in the preparation or prosecution of the application, and who are associated with the inventor, the applicant, an assignee, or anyone to whom there is an obligation to assign the application (see, e.g., 37 C.F.R. 1.63(c) and 37 C.F.R. 1.56).
Examiner notes that references utilized in Exhibits were not placed on record in an IDS in the Response filed 7/29/2026.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Amended claim 5 is representative of the pending claim scope and presently recites:
5. (Original) A method for stabilizing glycopeptide antibiotics, selected from the group consisting of vancomycin, telavancin, oritavancin, teicoplanin, dalbavancin and mixtures thereof, which involves addition of N-acetylated D-cysteine (D-aCys) to a solution comprising such glycopeptide antibiotics , or addition of glycopeptide antibiotics , to a solution comprising N-acetylated D-cysteine (D-aCys ), and wherein the resulting solution is present in a container having a headspace filled with an air-containing gas.
Accordingly, the claim is directed to a method, an the applicable claim interpretations are discussed below.
The preamble statement (“A method for stabilizing glycopeptide antibiotics”), per MPEP § 2111.02, “where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”. Here, the body of amended claim 5 is understood to recite a structurally complete invention, and therefore the preamble is deemed fully satisfied by prior art that satisfies the steps and structures recited in the body of the claim (see also MPEP § 2111.04(I), noting that “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”).
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
Amended claim 5 recites “headspace”, which is not defined in the originally filed disclosure, and is therefore given the broadest reasonable interpretation in the art, namely “headspace” is understood to be “the vapor that forms above or around a liquid or solid sample in a closed container”, wherein headspace analysis is typically performed using gas chromatography (see, e.g., Sithersingh5 at 14 at 1st ¶, 37 at 1st and 2nd ¶¶, 39 at 1st full ¶). Furthermore, the “headspace” gas contents can change over time and is dependent upon temperature and moisture (see, e.g., Sithersingh at 39-40 at bridging ¶ explaining that headspace analysis can be utilized to detect and monitor differences in headspace content due to improper storage temperatures; see also Wenger et al.6 at abs, 35-36 at bridging ¶, 36 at § Why must humidity be considered?, 37 at Fig. 1, showing that “dry” air at 20.9% O2 may actually correspond to 18.6% O2 in the presence of gaseous water and other components; see also Brueckner et al.7 at Fig. 1 on 25 and Fig. 4 on 28, showing headspace O2 changing over time). Accordingly, headspace contents can change over time and depend upon various factors.
Amended claim 5 recites “an air-containing gas”, which is not defined, or used in the originally filed disclosure. Upon review, the phrase “an air-containing gas” is not defined in the originally filed disclosure. The only literal “air-containing gas” utilized in the disclosure appears to be atmospheric “air” (see, e.g., Spec. filed 5/19/2023 at 3 at final ¶, 10-11 at bridging ¶, referring to “normal atmosphere” and “filled under atmospheric conditions”, reporting an O2 target with two significant digits). Accordingly, “an air-containing gas” presumably is a novel subgenus of gases that includes only the exemplified embodiment of normal atmospheric “air”. Therefore, for purposes of applying prior art, “an air-containing gas” is interpreted as including atmospheric “air”.
“Air” is used once in the specification to refer to “a suitable container with air as headspace”8, but “air” is not defined in the originally filed disclosure, which is pertinent because the specific level of O2 present appears critical to patentability. Accordingly, “air” is given the broadest reasonable interpretation in view of the specification, which implies that “air” is used to refer to atmospheric air9 (i.e., not “medical air”, “dry air”, “synthetic air”, etc.). Therefore, “air” is generally understood in the art to refer to a gas comprising “approximately 78% nitrogen, approximately 20% oxygen, and approximately 1% argon plus minor amounts of other gases” (see, e.g., US20180256717 at ¶[0254]), wherein “ambient air at sea level” includes “20.9% oxygen” (v/v) (see, e.g., US20170239289 A1 at ¶[0296]), and wherein the figure of 20.9% O2 (v/v) refers to “dry” air, but this percentage is actually lower (e.g., 18.6% (v/v)) if gaseous water (i.e., humidity in the atmosphere) is present10. Accordingly, for purposes of applying prior art, “air” is understood to refer to atmospheric air that, when dry, comprises 20.9% O2 (v/v), and when present with moisture, comprises less than 20.9% O2 (v/v).
Claims 8-9, 11, and 13 recite ranges modified by the term “about”, which is not defined on record. The term “about” lacks a set meaning in the biochemical arts and no agreed upon definition exists. More specifically “‘about’ can mean within 1 or more than 1 standard deviations” (see US 2012/0178676 at ¶[0277]); “about” can mean “within an order of magnitude” or “within 5-fold” of a value (see US 20130261065 at ¶[0031]); and can also mean “within 20 percent” (see, e.g., US 2009/0028832 A1 at ¶[0111]; see also US 2009/0105341 A1 at ¶[0049]). Accordingly, the metes and bounds of “about” in the instant usage is unspecified. For purposes of applying prior art, the term is understood to broadly mean “within 5-fold” or “within 20 percent” of a set value.
Newly added claims 7 and 13 recite “the gas has an oxygen content of up to 30%”. It is noted that the range “up to 30%” lacks a clear minimum value and therefore literally reads upon the range 0.0% to 30% O2; however, claim 1 and 13 require an “air-containing gas”, wherein “air” is understood to comprise approximately 20.9% O2 (v/v). However, “an air-containing gas” may only “contain” less than 0.001% of “air”, and therefore the ranges at claims 7 and 13 are reasonably deemed satisfied by any trace amounts of O2 (<0.0001% v/v) “up to 30%”. Therefore, it is unclear if “30%” refers to percent volume (% vol (v/v)), mass fraction (% wt/ w/w), or something else. For purposes of examination in view of the prior art, any percentage of “air-containing gas” having >0.0% up to 30% O2, regardless of unit, is presumed to fully satisfy the claim scope.
Additional claim interpretations are discussed below.
Withdrawn Claim Rejections
The rejection of claim 5 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of the amendments to claim 5 as filed 7/29/2026.
The rejection of claim 5 under 35 U.S.C. 103 as being unpatentable over US2017/0348385A1 (Dec. 7, 2017) is withdrawn in view of the amendments to claim 5 as filed 7/29/2026.
Examiner notes that the amendments filed 7/29/2026 have necessitated new and/or revised rejections, which are set forth below.
New or Revised Claim Rejections Necessitated by Applicant Amendment
Claim Rejections - 35 USC § 112(a), New Matter
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.
Claims 5-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicable Case Law
The MPEP states that "[w]hile there is no in haec verba requirment, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP 2163.
Lack of literal Support
The MPEP states that "[w]hile there is no in haec verba requirment, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP 2163.
Upon review, no literal support exists for amended claim 5 or newly added claim 13, which are representative of the pending claim scope. Specifically, the phrase “a headspace filled with an air-containing gas” does not literally appear in the originally filed disclosure.
Accordingly, claims 5-16 lack literal support in the originally filed disclosure.
Lack of Implicit or Inherent Support
The MPEP states that "[w]hile there is no in haec verba requirment, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP 2163. As noted above, the claims are not literally supported by the originally filed disclosure. Accordingly, the relevant issue is whether or not the new amendments and resulting claim scope is implicitly or inherently supported by the originally filed disclosure.
Per MPEP § 2163(I)(B), “[a]n amendment to correct an obvious error does not constitute new matter where the ordinary artisan would not only recognize the existence of the error in the specification, but also recognize the appropriate correction. In re Oda, 443 F.2d 1200, 170 USPQ 268 (CCPA 1971)”. Here, no allegation that the amendments correct an obvious error has been made. Furthermore, upon inspection, Examiner is unable to identify any single “obvious error” that would lead to the instantly amended claim scope. Accordingly, the amendments cannot be said to correct an “obvious error”.
Critically, “air-containing gas” is presumably not synonymous or equivalent to “air” (see, e.g., Nystrom v. TREX Co., Inc., 424 F. 3d 1136, 1143 (Fed. Cir. 2005), explaining that "When different words or phrases are used . . . a difference in meaning is presumed").
The meaning of “air-containing gas” is not provided on record, and therefore the phrase is interpreted literally as any gas that contains any amount of air, even trace amounts (i.e., a gas containing 0.0001% vol “air” and a gas containing 100% vol “air” are both literally “air-containing gases”). Accordingly, the scope of the genus of “air-containing gas” is vast and highly varied, and would include almost pure argon, nitrogen, helium, etc., so long as such gases contained a trace amount (>0.01%) of “air”.
However, at best, the originally filed disclosure exemplified embodiments of record utilizing only atmospheric air (see, e.g., Spec. filed 5/19/2023 at 10-11 at § Filling), wherein the oxygen concentration was “adjusted within a glovebox” (see id.) to a value of 0%, 10.5%, or to 21.0% oxygen (see, e.g., Spec. filed 5/19/2023 at 10 at lines 1-20). Accordingly, the disclosure of three types of oxygen-adjusted atmospheric air compositions cannot be said to inherently, literally, or implicitly extent to all possible methods of using any and all types of “air-containing gas”, such as 99.99% argon with 0.01% “air”.
Accordingly, the amended claim scope cannot be said to be literally, implicitly, or inherently supported by the originally filed disclosure.
Conclusion
Per MPEP § 2163, new or amended claims which introduce elements or limitations which are not supported by the as-filed disclosure violate the written description requirement (see, e.g., In re Lukach, 442 F.2d 967, 169 USPQ 795 (CCPA 1971)). Here, the newly added claim limitations are not inherently, implicitly, or literally supported by the originally filed disclosure.
Claims 5-16 are rejected.
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 7 and 16 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.
Newly added claims 7 and 16 recite “the gas has an oxygen content of up to 30%”, but no units are specified, which renders the claim scope indefinite because it is unclear if “30%” refers to percent volume (% vol (v/v)), mass fraction (% wt/ w/w), or something else, and the specific unit impacts the claim scope. Accordingly, the metes and bounds of these claims are currently unknown. For purposes of applying prior art, any percentage of “air-containing gas” having >0.0% up to 30% O2, regardless of unit, is presumed to fully satisfy the claim scope.
At claims 7 and 16, the claims recite the limitation "the gas" at line 1. There is insufficient antecedent basis for this limitation in the claim. Notably, “air” and “an air-containing gas” are both gases that may contain oxygen. For purposes of applying prior art, it is presumed that “gas” refers to “an air-containing gas”.
Accordingly, claims 7 and 16 are rejected.
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 5-16 are rejected under 35 U.S.C. 103 as being unpatentable over US2017/0348385A1 (Dec. 7, 2017) in view of Duncan et al.11
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above and in preceding rejections, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims 5-16, and methods of combining vancomycin with an N-acetyl-D-amino acid, and adjusting the pH to about 3-6 using HCl or NaOH, US’385 explicitly teaches and claims methods of making compositions comprising the glycopeptide antibiotic of vancomycin, wherein vancomycin is combined in aqueous solution with an N-acetyl-D-amino acid, and wherein the pH is adjusted to about 3-6 using HCl or NaOH (see, e.g., US'385 at ¶¶[0209]-[0211], [0220]-[0223], claims 1-4, 10-13, 34-47, 65, 69, 78, 81, 97, 114-118, 121-127). Regarding instant claims 5-6, 13-14, and the usage of vancomycin, US’385 explicitly teaches, exemplifies, and claims such methods and embodiments specifically utilizing vancomycin (see, e.g., US'385 at ¶¶[0209], [0211], [0220]-[0223], claims 10-11, 13, 69, 81, 117). Regarding instant claims 8 and a glycopeptide antibiotic concentration of “about 5.0 mg/mL”, US’385 explicitly teaches, exemplifies, and claims such methods wherein the concentration of the glycopeptide antibiotic is about 0.1-20% w/V (see, e.g., US’385 at ¶¶[0046], [0048], [0099]-[0100], [0112]-[0115], claims 118, 124-125), and US’385 explicitly directs artisans to make and use
[0142] Aqueous pharmaceutical compositions comprising about 0.5-15 % w/V glycopeptide antibiotic and an N-modified-D-amino acid in the molar ratio of about 1:1-1:30 having a pH of about 3-6 optionally further comprising an amino acid.
(see, e.g., US’385 at ¶[0142]).
This is pertinent because 0.5-15% w/V of vancomycin corresponds to 5 to 150 mg/mL of vancomycin12, which is understood to materially overlap with the range of “about 5.0 mg/mL” as presently claimed (see, e.g., MPEP § 2144.05(I), noting that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists). Regarding instant claims 9-10, and the presence of an N-acetylated-D-amino acid in a 20-35 fold molar surplus relative to vancomycin, or otherwise at a concentration of “between about 5 and about 20 mg/mL”, US’385 explicitly teaches, exemplifies, and claims such methods wherein the concentration of N-acetylated-D-amino acid is disclosed as within a molar ratio to the glycopeptide antibiotic (e.g., vancomycin) of about 0.5:1 to 40: 1 (see, e.g., US’385 at ¶¶[0100], [0142], [0220]-[0223], claims 124-126), wherein US’385 explicitly directs artisans to make and use
[0142] Aqueous pharmaceutical compositions comprising about 0.5-15 % w/V glycopeptide antibiotic and an N-modified-D-amino acid in the molar ratio of about 1:1-1:30 having a pH of about 3-6 optionally further comprising an amino acid.
(see, e.g., US’385 at ¶[0142]).
Notably, 0.5-15% w/V of vancomycin corresponds to 5 to 150 mg/mL of vancomycin13, a 0.5:1 to 40:1 concentration of an N-modified-D-amino acid such as N-acetyl-D-Cys would be approximately ~0.28 mg/mL to ~675.60 mg/mL14. However, using the exemplified embodiments as a guide, it is noted that in US’385 all exemplified embodiments using a molar ratio of 1:30 utilize only 0.5 % w/V of vancomycin (see, e.g., US’385 at [0220]-[0223]), which would direct artisans to a narrower range of approximately ~0.28 mg/mL to ~21.97 mg/mL15 of an N-modified-D-amino acid such as N-acetyl-D-Cys (see, e.g., MPEP § 2144.05(I), noting that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists). Regarding claims 11-13 and adjusting the pH to between about 4.0 to about 7.0 of an aqueous solution, US’385 explicitly directs artisans to make and use
[0142] Aqueous pharmaceutical compositions comprising about 0.5-15 % w/V glycopeptide antibiotic and an N-modified-D-amino acid in the molar ratio of about 1:1-1:30 having a pH of about 3-6 optionally further comprising an amino acid.
(see, e.g., US’385 at ¶[0142]).
Furthermore, US’385 expressly directs artisans to utilize aqueous solutions (see, e.g., US'385 at ¶¶[0209], [0211], [0220]-[0223], claims 3, 38, 114). Accordingly, utilizing aqueous solutions having a pH of “about 3-6” was explicitly taught by the prior art, and therefore does not weigh in favor of a determination of non-obviousness (see, e.g., MPEP § 2144.05(I), noting that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists).
US’385 differs from the amended and newly added claims as follows: Although US’385 teaches and directs artisans to methods of making aqueous solutions having a pH of about 3-6, comprising about 0.1-20% w/V of vancomycin and a molar ratio of vancomycin to N-modified-D-amino acids of 1:0.5 to 1:40, US’385 differs from the instant claims because
(i) the instant claims require the specific N-acetyl-D-amino acid of N-acetyl-D-Cys (NAC), rather than the N-acetyl-D-Ala as utilized by US’385; and
(ii) US’385 is silent regarding “a container having a headspace filled with an air-containing gas” having an “oxygen content of up to 30%” as presently claimed.
Accordingly, the relevant issue is whether or not the substitution of one N-acetyl-D-amino acid for another N-acetyl-D-amino acid in the prior art methodology of US’385, and using “air” in a container is sufficient to render the claimed invention non-obvious in view of the prior art.
Regarding the usage of N-acetyl-D-Cys (NAC) and a glycopeptide antibiotic (e.g., vancomycin), US'385 explicitly teaches and discloses methods of making compositions comprising a glycopeptide antibiotic, such as vancomycin, in combination with an N-acetyl-D-amino acid, having a pH of about 3-6, wherein N-acetyl-D-Ala is exemplified (see, e.g., US'385 at claims 1-4, 10-13, 34-47, 65, 69, 78, 81, 97; see esp. id. at claims 78). Although US'385 does not exemplify the combination of N-acetyl-D-Cys and a glycopeptide antibiotic (e.g., vancomycin), such combinations are obvious variants of the disclosed and claimed inventions of US'385 in view of the disclosure as a whole because US'385 identifies that the disclosed invention pertains to any and all "glycopeptide antibiotic compositions comprising an N-acetyl-D-amino acid” (see, e.g., US'385 at ¶¶[0020]-[0022]), and any "method for stabilizing glycopeptide antibiotics which involves addition of N-acetyl-D-amino acids to a solution comprising a glycopeptide antibiotic or addition of a glycopeptide antibiotic to a solution comprising N-acetyl-D-amino acids" (see, e.g., US'385 at ¶¶[0036]), wherein US’385 explicitly directs artisans to make and use
[0142] Aqueous pharmaceutical compositions comprising about 0.5-15 % w/V glycopeptide antibiotic and an N-modified-D-amino acid in the molar ratio of about 1:1-1:30 having a pH of about 3-6 optionally further comprising an amino acid.
(see, e.g., US’385 at ¶[0142]).
This is pertinent because the meaning and structures of N-acetyl-D-amino acids contemplated by US'385 are unambiguously identified (see, e.g., US'385 at ¶[0071]), and explicitly include all α-amino acid side chains, including D-Cysteine (see id; see also US'385 at ¶¶[0066], [0068]). Accordingly, an artisan would readily appreciate that the disclosure broader informed and taught artisans of methods for forming stabilized vancomycin compositions that could be predictably and desirably practiced with any N-acetyl-D-amino acid, including N-acetyl-D-Cys as instantly claimed (see, e.g., US'385 at ¶¶[0036], [0066], [0068], [0071]). Therefore, US’385 unambiguously informs artisans that all “N-acetyl-D-amino acids” are functional equivalents for use in aqueous solutions (see, e.g., US’385 at ¶¶[0141]-[0144]), methods of stabilizing glycopeptide antibiotics (see, e.g., US’385 at ¶[0036]), and in methods of treating bacterial infections (see, e.g., US’385 at ¶¶[0020]-[0022]). Accordingly, the predicted and expected results of simply substituting one N-acetyl-D-amino acid disclosed by US’385 for another disclosed by US’385 would merely be predicted and expected to be approximately the same as the results shown for N-acetyl-D-Ala (see US'385 at ¶[0220]-[0223]).
Regarding amended claim 5, 7, 13, and “a container having a headspace filled with an air-containing gas”, although US’385 is silent regarding a “headspace filled with an air-containing gas”, US’385 expressly directs artisans to pack resulting compositions in “ready to use” containers and kits comprising containers holding solutions of the invention (see, e.g., US’385 at ¶¶[0035], [0079], [0205]-[0206), but is silent regarding headspace and air. However, in the absence of direct guidance away from packaging in a specialized gas, artisans would reasonably practice the invention of US’385 using routine and cost-effective pharmaceutical packaging techniques in the art. Furthermore,
Pharmaceutical containers are well-understood by artisans to routinely contain a headspace (see, e.g., Duncan at title, abs, 230-231 at bridging ¶);
It is well-understood that a headspace may comprise “atmospheric air” or “sterile air” (see, e.g., Duncan at 236 at col II at § Chemical Oxidation of the TSB; 234-235 at bridging ¶);
It is well-understood that “atmospheric air” contains oxygen (see, e.g., Duncan at 236 at col II at § Chemical Oxidation of the TSB);
An artisan would readily appreciate that when oxygen in a headspace is derived from “atmospheric air”, although it would initially be expected to be approximately 20.9% atm (see id. at 236 at col II), that this number was high due to moisture/water effects, and therefore the measured level of O2 would be measured lower than 20.9 % atm, such as 19.8% atm or even 17.9% atm (see id. at 238-239 at bridging ¶, Figures 1-7 at time zero); and
An artisan would readily appreciate that measurements of O2 content in the headspace of pharmaceutical containers was routine in the prior art, and used for quality control and detection of contamination (see, e.g., Duncan at title, abs, 230-231 at bridging ¶).
Accordingly, Duncan is cited herein to establish that pharmaceutical containers are well-understood to have a headspace, that the headspace may contain atmospheric oxygen at approximately 17.9% atm to 20.9 % atm, and that oxygen levels may be monitored, wherein changes over time are indicative of contamination such as microbial growth (see, e.g., Duncan at 238 at Fig. 1-4, 239 at 5-7, 238 at col. I at 1st full ¶ to 239 at 1st partial ¶). In sum, the limitations at claims 5, 7, 13, regarding a “container having a headspace filled with an air-containing gas” appears to reflect standard and routine conditions in the pharmaceutical packaging arts, which would be routinely practiced by following the guidance of US’385 and packaging the resulting compositions in kits and containers as explicitly taught by the prior art. Accordingly, the predicted and expected results of simply packaging the disclosed compositions of US’385 using standard pharmaceutical packaging techniques and sterile atmospheric air, would be a packaged composition comprising a headspace containing air, and more specifically ~17.9% to 20.9% atm of oxygen (see US'385 at ¶[0220]-[0223]), wherein such packaged compositions could be predictably utilized in the methods, products, and treatments disclosed and suggested by US’385.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed invention is combination of prior art elements (i.e., the N-acetyl-D-amino acid of N-acetyl-D-Cys; the glycopeptide antibiotic of vancomycin; pH adjusters such as HCl and NaOH, atmospheric air) according to known methods of forming stabilized compositions as taught and suggested by US’385, and according to known methods of pharmaceutical packaging as exemplified and suggested in view of US’385 and Duncan, wherein such combination would predictably and expectedly yield a method of stabilizing a glycopeptide antibiotic, exactly as taught and suggested in view of the prior art, wherein the final product would have a headspace comprising sterile atmospheric oxygen per routine practices in the pharmaceutical packing arts as established by Duncan (see, e.g., MPEP § 2143(I)(A), (B), (C), (D), (F), and (G), because all of the N-acetyl-D-amino acids explicitly disclosed by US’385 are reasonably inferred and predicted to be functional equivalents and pharmaceutical packaging is routine in the art (see, e.g., MPEP § 2144.06(II)).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to practice a known prior art method of stabilizing glycopeptides by combining a known glycopeptide with a known N-acetyl-D-amino acids, to achieve the exact outcome taught, disclosed, and suggested by the prior art.
Claims 5-16 are rejected.
Response to Arguments
Applicant's arguments filed 7/29/2026 have been fully considered but they are not persuasive. Examiner notes that multiple arguments raised by the Applicant have been rendered moot in view of the new and/or revised rejections above; remaining applicable arguments are addressed below.
Allegations that a limitation was not considered in view of the single reference of US2017/0348385A1: It is the Examiner’s understanding that Applicant is alleging that the prior rejection of record did not address the newly added claim limitations set forth in the new and amended claim set filed 7/29/2026 (see, e.g., Reply filed 7/29/2026 at 8 at final ¶ to 9 at 1st full ¶, discussing “headspace filled with an air-containing gas”). It is undisputed that this limitation was not previously considered as it was added in the Reply filed 7/29/2026. The limitation is now directly addressed in view of the new rejection under 35 USC 103 over US’385 in view of Duncan. Note that 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). Accordingly, the new limitations are directly addressed in the revised/new rejection of record. Specifically, although US’385 is silent regarding a “headspace filled with an air-containing gas”, US’385 expressly directs artisans to pack resulting compositions in “ready to use” containers and kits comprising containers holding solutions of the invention (see, e.g., US’385 at ¶¶[0035], [0079], [0205]-[0206), which would be understood to include a headspace per Duncan. Furthermore, in view of Duncan, packaging in atmospheric air would be understood to be obvious and routine in the art.
Repeating issues raised and supported by a Declaration: It is the Examiner’s understanding that Applicant reiterates issues and arguments raised in the Declaration filed 7/29/2026 by Hessenberger (see, e.g., Reply filed 7/29/2026 at 7 at 2nd full ¶ to page 9 at 2nd full ¶, alleging that the “Examiner’s obvious rationale” depends upon an incorrect premise, based upon ¶¶12-15, 19-25 of the Hessenberger Declaration, and repeating the declaration almost verbatim). These arguments are addressed a single time in view of the Declaration, in a separate section below. In brief, these arguments have been fully considered but not found persuasive.
Applicant’s position regarding the substitutions of N-acetyl-D-cysteine and N-acetyl-D-alanine are premised upon simply dismissing the teachings of US2017/0348385A1: It is the Examiner’s understanding that Applicant’s arguments substantially reply upon a dismissal of the express guidance and disclosures of US’385, by alleging that N-acetyl-D-cysteine and N-acetyl-D-alanine would not be considered functional equivalents by artisans (see, e.g., Reply filed 7/29/2026 at 7 at 2nd full ¶ to page 9 at 2nd full ¶, alleging that the “Examiner’s obvious rationale” depends upon an incorrect premise), and therefore substitution of one for the other is allegedly not a “simple substitution” (see id. at 9 at 1st full ¶, starting with “Because”). In direct contrast to the Applicant’s assertions, US’385 expressly informs artisans to make and use aqueous compositions with any glycopeptide antibiotic and any N-modified-D-amino acid:
[0142] Aqueous pharmaceutical compositions comprising about 0.5-15 % w/V glycopeptide antibiotic and an N-modified-D-amino acid in the molar ratio of about 1:1-1:30 having a pH of about 3-6 optionally further comprising an amino acid.
(see, e.g., US’385 at ¶[0142]; see also id. at ¶¶[0141]-[0144]).
Wherein the invention includes methods for stabilizing glycopeptide antibiotics using any “N-acetyl-D-amino acid” without limit:
[0036 ] The present invention further provides a method for stabilizing glycopeptide antibiotics which involves addition of N-acetyl-D-amino acids to a solution comprising a glycopeptide antibiotic or addition of a glycopeptide antibiotic to a solution comprising N-acetyl-D-amino acids.
(see, e.g., US’385 at ¶[0036]).
Wherein “N-acetyl-D-amino acids” is a term explicitly defined to include any amino acids (see, e.g., US’385 at ¶¶[0071]-[0072]), expressly including “D-Cysteine” (see, e.g., US’385 at ¶¶[0066], [0068]). Furthermore, US’385 explicitly refers to the exemplified embodiments applying to all “N-acetyl-amino acids”, wherein all “N-acetyl-amino acids” would stabilize vancomycin relative to N-acetylated di- and tri-peptides (see, e.g., US’385 at ¶[0227]), and US’385 explicitly teaches that such compositions, using any N-acetyl-D-amino acid, would be usable as a medicament for use in treating bacterial infections (see, e.g., US’385 at ¶¶[0020]-[0022], [0036]). Accordingly, all arguments proffered by Applicant regarding the alleged differences between N-acetyl-D-cysteine and N-acetyl-D-alanine (see, e.g., Reply filed 7/29/2026 at 7 at 2nd full ¶ to page 9 at 2nd full ¶) fail to address the express teachings of the prior art, which expressly directs artisans to methods of stabilizing glycopeptide antibiotics using any “N-acetyl-D-amino acid”, without limitation. Accordingly, the prior art clearly, expressly, and unambiguously identifies all “N-acetyl-D-amino acids” as functional equivalents for use in aqueous solutions (see, e.g., US’385 at ¶¶[0141]-[0144]), methods of stabilizing glycopeptide antibiotics (see, e.g., US’385 at ¶[0036]), and methods of treating bacterial infections (see, e.g., US’385 at ¶¶[0020]-[0022]). All arguments failing to directly address such explicit teachings and express prior art guidance amount to an attempt to simply ignore or dismiss the teachings of US’385. Arguments premised upon dismissing the express guidance of the prior art is not persuasive because, per MPEP § 2141.03, “The person of ordinary skill in the art is a hypothetical person who is presumed to have known the relevant art at the relevant time” (see, e.g., MPEP § 2141.03(I)). Here, the Applicant does not dispute that all references constitute “prior art”. Furthermore, the Applicant does not dispute that prior art pertaining to N-acetyl-D-amino acid stabilization of glycopeptide antibiotics is “relevant art”, Therefore, the entire reference constitutes “relevant art” available “at the relevant time”. Accordingly, arguments suggesting that a reasonable artisan in the arts would be unaware of US’385 or otherwise arguments premised upon just dismissing or ignoring US’385 completely is not persuasive. The reference at issue is applicable prior art, and therefore presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)). Here, it does more than “suggest” the use of N-acetyl-D-amino acids such as NAC, but instead expressly teaches such combinations.
Allegations suggesting “inoperability” or lack of enabling disclosure regarding a prior art reference: It is the Examiner’s understanding that Applicant’s statements amount to a suggestion that the prior art is not fully enabled or operable (see, e.g., Reply filed 7/29/2026 at 7 at 2nd full ¶ to page 9 at 2nd full ¶, alleging that the “Examiner’s obvious rationale” depends upon an incorrect premise), because Applicant appears to allege that, in direct contradiction to the express teachings of US’385, which identifies all “N-acetyl-D-amino acids” as functional equivalents for use in aqueous solutions (see, e.g., US’385 at ¶¶[0141]-[0144]), methods of stabilizing glycopeptide antibiotics (see, e.g., US’385 at ¶[0036]), and methods of treating bacterial infections (see, e.g., US’385 at ¶¶[0020]-[0022]), that such substitutions were not predictable in view of the prior art. If Applicant is attempting to allege that the prior art is not enabling or inoperable Applicant is directed to MPEP § 2121(I), which notes that the prior art is presumed fully enabled for all that it discloses, and the burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). No evidence of inoperability commensurate in scope with the requirements of MPEP § 716.07 have been placed on record at this time; critically, arguments of counsel cannot take the place of evidence in the record (see, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965), and evidence is required to rebut the presumption of operability. The Examiner’s position is that the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)). Accordingly, the Applicant has not satisfied their burden to rebut the presumption of operability of the prior art at this time (see, e.g., MPEP § 2121(I); MPEP § 716.07).
Allegations suggesting “skepticism of experts”: It is the Examiner’s understanding that Applicant’s statements amount to a suggestion that the Examiner’s position would be met with skepticism of experts (see, e.g., Reply filed 7/29/2026 at 7 at 2nd full ¶ to page 9 at 2nd full ¶, alleging that the “Examiner’s obvious rationale” depends upon an incorrect premise), because Applicant appears to allege that, in direct contradiction to the express teachings of US’385, which identifies all “N-acetyl-D-amino acids” as functional equivalents for use in aqueous solutions (see, e.g., US’385 at ¶¶[0141]-[0144]), methods of stabilizing glycopeptide antibiotics (see, e.g., US’385 at ¶[0036]), and methods of treating bacterial infections (see, e.g., US’385 at ¶¶[0020]-[0022]), that such substitutions would not have yielded predictable results to artisans (see Reply filed 7/29/2026 at 8 at 2nd ¶, 9 at 1st partial to 1st full ¶¶, alleging what “the skilled person would have expected”). Critically, Applicants assertions regarding what an artisan “would have expected” conveniently ignore the explicit teachings of US’385, which explicitly teach and suggest that any and all “N-acetyl-D-amino acids”, which includes NAC, could be predictably and expectedly utilized in methods of stabilizing glycopeptide antibiotics, which is exactly what Applicant appears to allege is “surprising”. If Applicant means to suggest the existence of skepticism of experts, such evidence should be filed per MPEP § 716.05 as evidence is required to establish skepticism of experts. In the absence of such evidence, such statements are understood to be unsupported conjecture of counsel. The prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)), and no objective evidence rebutting this presumption has been placed on record to date.
Allegations suggesting the references “teach away”: It is the Examiner’s understanding that Applicant is suggesting that the references “teach away” from the claimed invention (see, e.g., Reply filed 7/29/2026 at 7 at 2nd full ¶ to page 9 at 2nd full ¶). Examiner notes that this argument is not persuasive because none of prior art references at issue “teach away” from the claimed invention since they do not actually “criticize, discredit, or otherwise discourage the solution claimed” (see, e.g., MPEP § 2141.02(VI)). Applicant has not identified any disclosure that “criticizes, discredits, or otherwise discourages the solution claimed”, as the prior art explicitly teaches such combination (see, e.g., US’385 at ¶¶[0020]-[0022], [0036], [0141]-[0144]). Accordingly, no “teaching away” has been identified on record.
Allegations suggesting “lack of predictability” or “lack of reasonable expectation of success”: It is the Examiner’s understanding that Applicant is alleging a lack of predictability or otherwise a lack of reasonable expectation of success (see, e.g., Reply filed 7/29/2026 at 7 at 2nd full ¶ to page 9 at 2nd full ¶, alleging that the “Examiner’s obvious rationale” depends upon an incorrect premise; see also Reply filed 7/29/2026 at 8 at 2nd ¶, 9 at 1st partial to 1st full ¶¶, alleging what “the skilled person would have expected”, and alleging the expectation of using NAC would have been “to increase chemical reactivity and potential oxidative instability”). This is not persuasive because the Applicant’s assertions do not reflect the proper legal standards for evaluating predictability. MPEP § 2143.02(II) explains that “[o]bviousness does not require absolute predictability”, but instead clarifies that only “at least some degree of predictability is required” (see, e.g., MPEP § 2143.02(II)). Here, the rejection explicitly addresses predictability and reasonable expectation of success, but Applicant fails to address the explicitly identified predicted and expected results set forth in the rejection. Here, the Examiner’s basis for “predictability” is merely based upon the presumption that the prior art is fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). As explained at MPEP § 2143.02, predictability and reasonable expectation of success are satisfied when “all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art”. Here zero evidence of unexpected results commensurate in scope with the requirements of MPEP 716.02 have been set forth on record, all elements of the claimed invention were known in the prior art, the art provided express guidance to utilize any N-acetyl D-amino acid to stabilize glycopeptide antibiotics, and one of ordinary skill was fully enabled to combined each component using routine methods in the biochemical arts per the guidance of the primary reference, and the elements would have merely performed their art-recognized, respective functions (see Rejection, above). Accordingly, such arguments are not persuasive. The courts have previously noted that "[r]eading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." (see, e.g., Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327 (1945), at 335), and the Court has further stated that
"[W]hen a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious."
KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 , 417 , 127 S. Ct. 1727 , 167 L. Ed. 2d 705 (2007) (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273 , 282 , 96 S. Ct. 1532 , 47 L. Ed. 2d 784 (1976)).
Likewise, the Supreme Court has rejected rigid tests for obviousness and has emphasized that
[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.”
KSR Int'l v. Teleflex Inc., 550 U.S. 398, 415 (2007), at 416.
And has also emphasized that
“If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.”
KSR Int'l v. Teleflex Inc., 550 U.S. 398, 415 (2007), at 417.
Here, all aspects of the claimed method were already known in the art, including each component and methods of combining each component, wherein the prior art provided clear predicted and expected outcomes from the performance of such methods. Accordingly, the mere fact that the prior art teaches and informs artisans that multiple N-acetyl-D-amino acids could be utilized in such stabilization methods with a reasonable expectation of success, does not weigh in Applicant’s favor because all such combinations of glycopeptide antibiotics with any N-acetyl-D-amino acids was presumed fully enabled (see, e.g., MPEP § 2121(I); §§ 2123(I)-(II)). Accordingly, the fact that the prior art provides a broad teaching does not render that teaching inoperable or less predictable. Accordingly, claiming prior art methods of using known compounds for known purposes using the same or overlapping steps of adjusting pH, exactly as taught and suggested by the prior art, to achieve the exact same results achieved and suggested by the prior art, weighs in favor of a determination of obviousness.
Allegations of unexpected results commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02: It is the Examiner’s understanding that Applicant alleges the existence of unexpected results commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02, wherein such results are sufficient to rebut prima facie obviousness (see, e.g., Reply filed 7/29/2026 at 8 at 3rd to 4th ¶¶, alleging “This is a surprising result”). However, to establish such unexpected results, the allegations must be timely and supported by objective evidence (see, e.g., 37 C.F.R. 1.132; see MPEP §§ 716.01, 716.01(a), 716.01(c)); to be of probative value the proffered evidence must be related to the claimed invention (see MPEP §§ 716.01(b), discussing nexus requirement and noting that "[w]here the offered secondary consideration actually results from something other than what is both claimed and novel in the claim, there is no nexus to the merits of the claimed invention"); the evidence must establish that the expected results occur to an unexpected extent (see, e.g., MPEP § 716.02(a)(I)), on the basis of statistically and practically significant evidence (see, e.g., MPEP § 716.02(b)(I)), which is fully explained (see, e.g., MPEP § 716.02(b)(II)), commensurate in scope with the claimed invention (see, e.g., MPEP § 716.02(d)), and wherein a comparison of the claimed invention with the closest prior art of record is provided (see, e.g., MPEP § 716.02(e)). Furthermore, even if evidence satisfying MPEP §§ 716.02, 716.02(a), 716.02(b), 716.02(d), and 716.02(e) is set forth on record, such evidence may not be sufficient to rebut prima facie obviousness because the evidence of expected and unexpected results must be weighed (see, e.g., MPEP § 716.02(c)(I)) and the totality of the record considered (see, e.g., MPEP §§ 716.01(d), 716.02(f)), including teachings in the prior art and evidence of expected results which weigh in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)). Here, the proffered data is insufficient to establish unexpected results commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02, at least because
(i) the proffered data is of unknown statistical and practical significance in the absence of proper controls for each experimental condition and in the absence of any identified statistical test, indication of experimental variability, or p-value (see, e.g., MPEP § 716.02(b)(I), § 716.02(b)(II));
(ii) the proffered data is not commensurate in scope with the instantly claimed invention, as instant claims 5 and 13 read upon a vast and highly varied array of gases (e.g., 99% O2 + 1% “air”, 99.9% argon + 0.1% “air”, etc.) , mixtures of glycopeptide antibiotics, pH ranges of 1-14 (see instant claim 1), temperature ranges of 0-50+ °C, etc., etc.; in addition, Applicant is directed to the definition and interpretation of “about” as set forth in the claim interpretation section above (see, e.g., MPEP § 716.02(d));
(iii) the proffered data does not unambiguously compare the claimed invention to the closest prior art, which appears to inherently and implicitly be made in atmospheric air and would be readily understood to inherently contain a headspace (see, e.g., US’385 at examples; see, e.g., MPEP § 716.02(e)); and
(iv) here, the proffered data appears to show the exact result taught, predicted, and expected in view of US’385, namely that glycopeptide antibiotics are stabilized in the presence of an N-acetyl-D-amino acid (see, e.g., US’385 at ¶¶[0020]-[0022], [0036], [0141]-[0144]), and data confirming the expected results weighs in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)).
Accordingly, no evidence of unexpected results commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02 have been identified or placed on record at this time, and the only proffered evidence of record is of unknown statistical significance but appears to show the exact result taught and expected in view of the US’385 disclosure. Evidence supporting the expectations of the prior art cannot reasonably be said to be “surprising” or “unexpected”.
In sum, all arguments raised by the Applicant have been fully considered, and all applicable arguments have been addressed above. However, such arguments are not persuasive and do not establish patentability or non-obviousness in view of the new rejections set forth above. All new rejections were necessitated by Applicant’s amendments.
Response to Declarations of Hessenberger under 37 C.F.R. §1.132
The affidavit under 37 CFR 1.132 filed 7/29/2026 is insufficient to overcome the rejections of record. A detailed explanation of why the affidavits or declarations are insufficient is provided below. The legal standards of review and consideration of Declarations under 37 C.F.R. §1.132 are discussed at MPEP § 716.01.
Interest of the Expert in the Outcome of the Case
Per MPEP 716.01(c)(III), in assessing the probative value of an expert opinion, the examiner must consider the interest of the expert in the outcome of the case. Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281, 227 USPQ 657 (Fed. Cir. 1985), cert, denied, 475 U.S. 1017 (1986). Here, the declarant is a named inventor and therefore has a clear interest in the outcome of the case.
Nature of the Matter Sought to be Established
Per MPEP 716.01(c)(III), in assessing the probative value of an expert opinion, the examiner must consider the nature of the matter sought to be established. Ashland Oil, Inc., 776 F.2d 281.
Here, it is understood that the Declarant seeks to establish:
inoperability of US2017/0348385A1 commensurate in scope with the requirements of MPEP § 716.07 (see, e.g., Dec. filed 7/29/2026 at ¶¶12-15, 17-23; alleging that “The thiol group of N-acetyl-D-cysteine is highly susceptible to oxidation in the presence of oxygen”, and that “The skilled person would have expected that introducing N-acetyl-D-cysteine into a solution of glycopeptide antibiotics stored under air-containing gas (i.e., with oxygen in the headspace) would result in oxidative degradation of the cysteine-derived excipient, loss of its stabilizing capacity, and acceleration of degradation of glycopeptide antibiotics. The skilled person would not have had a reasonable expectation of success 1n achieving stabilization of glycopeptide antibiotics using N-acetyl-D-cysteine under these conditions”);
the existence of skepticism of experts commensurate in scope with the requirements of MPEP § 716.05 (see, e.g., Dec. filed 7/29/2026 at ¶¶12-15, 17-23, alleging that “A person of ordinary skill in the art would have expected instability, not stabilization from N-acetyl-D-Cysteine in an oxygen-containing environment” and “The skilled person would have expected that introducing N-acetyl-D-cysteine into a solution of glycopeptide antibiotics stored under air-containing gas (i.e., with oxygen in the headspace) would result in oxidative degradation of the cysteine-derived excipient, loss of its stabilizing capacity, and acceleration of degradation of glycopeptide antibiotics. The skilled person would not have had a reasonable expectation of success 1n achieving stabilization of glycopeptide antibiotics using N-acetyl-D-cysteine under these conditions”);
the existence of unexpected results commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02 (see, e.g., Dec. filed 7/29/2026 at ¶¶24-25); and
patentability of the amended claim scope relative to the teachings of US2017/0348385A1 in view of the fact that US’385 is silent regarding headspace containing an air-containing gas (see, e.g., Dec. filed 7/29/2026 at ¶¶7-10, 16-17, 23-25).
The legal requirements for establishing inoperability are discussed at MPEP § 716.07; the legal requirements for establishing skepticism of experts is set forth at MPEP § 716.05; and the legal requirements for establishing unexpected results sufficient to rebut prima facie obviousness are discussed at MPEP §716, §716.01, and §716.02.
Opinions as to Legal Conclusions
As an initial matter, Examiner notes that per MPEP 716.01(c)(III), any opinions expressed by Declarant regarding legal conclusions are not entitled to any weight. However, the underlying basis for any opinion as to legal conclusions has been fully considered as detailed below. Regarding (iv) above, opinions regarding patentability are not entitled to any weight, but the underlying basis for the opinion has been fully considered as detailed below.
Presence or absence of factual support for the expert’s opinion
Per MPEP 716.01(c)(III), in assessing the probative value of an expert opinion, the examiner must consider the presence or absence of factual support for the expert’s opinion. Ashland Oil, Inc., 776 F.2d 281.
Inoperability of US2017/0348385A1
It is the Examiner’s understanding that Declarant is alleging and attempting to establish that the teachings, disclosure, and guidance of US’385 is incorrect, and that US’385 is inoperable (see, e.g., Dec. filed 7/29/2026 at ¶¶12-15, 17-23; alleging that “The thiol group of N-acetyl-D-cysteine is highly susceptible to oxidation in the presence of oxygen”, and that “The skilled person would have expected that introducing N-acetyl-D-cysteine into a solution of glycopeptide antibiotics stored under air-containing gas (i.e., with oxygen in the headspace) would result in oxidative degradation of the cysteine-derived excipient, loss of its stabilizing capacity, and acceleration of degradation of glycopeptide antibiotics. The skilled person would not have had a reasonable expectation of success 1n achieving stabilization of glycopeptide antibiotics using N-acetyl-D-cysteine under these conditions”).
All arguments raised and all references relied upon by the Declarant have been fully considered, but not found persuasive as explained below.
As an initial matter, the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)). Here, US’385 expressly informs artisans to make and use aqueous compositions with any glycopeptide antibiotic and any N-modified-D-amino acid:
[0142] Aqueous pharmaceutical compositions comprising about 0.5-15 % w/V glycopeptide antibiotic and an N-modified-D-amino acid in the molar ratio of about 1:1-1:30 having a pH of about 3-6 optionally further comprising an amino acid.
(see, e.g., US’385 at ¶[0142]; see also id. at ¶¶[0141]-[0144]).
US’385 expressly includes methods for stabilizing any glycopeptide antibiotics using any “N-acetyl-D-amino acid” without limit:
[0036 ] The present invention further provides a method for stabilizing glycopeptide antibiotics which involves addition of N-acetyl-D-amino acids to a solution comprising a glycopeptide antibiotic or addition of a glycopeptide antibiotic to a solution comprising N-acetyl-D-amino acids.
(see, e.g., US’385 at ¶[0036]).
Critically, “N-acetyl-D-amino acids” is a term explicitly defined to include any amino acids (see, e.g., US’385 at ¶¶[0071]-[0072]), expressly including “D-Cysteine” (see, e.g., US’385 at ¶¶[0066], [0068]). Furthermore, US’385 explicitly refers to the exemplified embodiments applying to all “N-acetyl-amino acids”, wherein all “N-acetyl-amino acids” would stabilize vancomycin relative to N-acetylated di- and tri-peptides (see, e.g., US’385 at ¶[0227]), and US’385 explicitly teaches that such compositions, using any N-acetyl-D-amino acid, would be usable as a medicament for use in treating bacterial infections (see, e.g., US’385 at ¶¶[0020]-[0022], [0036]). Accordingly, all arguments proffered by Applicant regarding the alleged differences between N-acetyl-D-cysteine and N-acetyl-D-alanine (see, e.g., Reply filed 7/29/2026 at 7 at 2nd full ¶ to page 9 at 2nd full ¶) fail to address the express teachings of the prior art, which expressly directs artisans to methods of stabilizing glycopeptide antibiotics using any “N-acetyl-D-amino acid”, without limitation. Accordingly, the prior art clearly, expressly, and unambiguously identifies all “N-acetyl-D-amino acids” as functional equivalents for use in aqueous solutions (see, e.g., US’385 at ¶¶[0141]-[0144]), methods of stabilizing glycopeptide antibiotics (see, e.g., US’385 at ¶[0036]), and methods of treating bacterial infections (see, e.g., US’385 at ¶¶[0020]-[0022]). Accordingly, US’385 is presumed fully enabled for all that it discloses or reasonably suggests (see, e.g., MPEP §§ 2123(I)-(II)), including for methods of using any N-acetyl-D-amino acid, including NAC, in stabilization methods for stabilizing any glycopeptide antibiotics.
Per MPEP § 716.07, “affidavits or declarations attacking the operability of a patent cited as a reference must rebut the presumption of operability by a preponderance of the evidence”. Here, the proffered argument rests upon an assumption that the stabilization methods of US’385 require “inert” amino acids to achieve stabilization (see, e.g., Dec. filed 7/29/2026 at ¶¶12-15, 17-23). Zero evidence supporting this assumption is provided, and this assumption is directly contradicted by the explicit disclosure of US’385 (see discussion in previous paragraph). Accordingly, arguments premised upon Shihong et al. and Poole address a difference between alanine and cysteine in oxidative environments, but no evidence that such difference is relevant to the disclosed methods of US’385 is actually set forth on record.
Per MPEP § 716.07,
Further, since in a patent it is presumed that a process if used by one skilled in the art will produce the product or result described therein, such presumption is not overcome by a mere showing that it is possible to operate within the disclosure without obtaining the alleged product. In re Weber, 405 F.2d 1403, 160 USPQ 549 (CCPA 1969). It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker. The failures of experimenters who have no interest in succeeding should not be accorded great weight. In re Michalek, 162 F.2d 229, 74 USPQ 107 (CCPA 1947); In re Reid, 179 F.2d 998, 84 USPQ 478 (CCPA 1950).
Here, zero evidence that the described process of US’385, using any N-acetyl-D-amino acids (i.e., NAC, N-acetyl-Alanine, N-acetyl glycine, etc.) with any glycopeptide antibiotic, is inoperable or fails to achieve stabilization exactly as explicitly taught and disclosed by US’385
(see, e.g., US’385 at ¶¶[0020]-[0022], [0036], [0141]-[0144]) has been placed on record at all. Rather, the proffered evidence shows that the obtained results are exactly what was predicted and expected in view of the disclosure of US’385, namely the successful stabilization of a glycopeptide antibiotic upon addition of an N-acetyl-D-amino acids. Accordingly, the proffered evidence does not support “inoperability” with any evidence, much less a preponderance of the evidence.
Per MPEP § 716.07, “Where the affidavit or declaration presented asserts that the reference relied upon is inoperative, the claims represented by applicant must distinguish from the alleged inoperative reference disclosure. In re Crosby, 157 F.2d 198, 71 USPQ 73 (CCPA 1946)”. Upon inspection, the declaration fails to distinguish how the pending claims distinguish from the alleged inoperative reference disclosure, since the pending claims literally recite a species of achieving stabilization of a glycopeptide antibiotic by addition of a species of N-acetyl-D-amino acid, exactly as taught and suggested by the prior art (see, e.g., US’385 at ¶¶[0020]-[0022], [0036], [0141]-[0144]).
Accordingly, all proffered arguments and evidence have been fully considered, but such evidence is not commensurate in scope with the requirements of MPEP § 716.07, and therefore fail to establish inoperability of the prior art.
Skepticism of Experts
It is the Examiner’s understanding that Declarant is alleging and attempting to establish that the teachings, disclosure, and guidance of US’385 would be met by skepticism of experts commensurate in scope with the requirements of MPEP § 716.05 (see, e.g., Dec. filed 7/29/2026 at ¶¶12-15, 17-23, alleging that “A person of ordinary skill in the art would have expected instability, not stabilization from N-acetyl-D-Cysteine in an oxygen-containing environment” and “The skilled person would have expected that introducing N-acetyl-D-cysteine into a solution of glycopeptide antibiotics stored under air-containing gas (i.e., with oxygen in the headspace) would result in oxidative degradation of the cysteine-derived excipient, loss of its stabilizing capacity, and acceleration of degradation of glycopeptide antibiotics. The skilled person would not have had a reasonable expectation of success 1n achieving stabilization of glycopeptide antibiotics using N-acetyl-D-cysteine under these conditions”).
All arguments raised and all references relied upon by the Declarant have been fully considered, but not found persuasive as explained below.
Per MPEP § 716.05, "The skepticism of an expert, expressed before these inventors proved him wrong, is entitled to fair evidentiary weight, . . . as are the five to six years of research that preceded the claimed invention." Here, Declarant relies upon Poole, published in 2015, and Li et al., published in 1995, to generally discuss cysteine and oxidation, and the alleged expectations of artisans with respect to the claimed invention (see, e.g., Dec. filed 7/29/2026 at ¶¶12-15, 17-23). These arguments are insufficient to support the existence of skepticism of an expert commensurate in scope with the requirements of MPEP § 716.05 as follows:
First, neither the Declarant nor Poole or Li et al. address the explicit teachings of US’385, or identify any explicit "Expressions of disbelief by experts” regarding the instantly claimed invention “expressed before these inventors proved him wrong” (see, e.g., MPEP § 716.05).
Second, in direct contrast to the existence of any “skepticism of an expert, expressed before these inventors proved him wrong”, US’385 explicitly directed artisans to methods of stabilizing any glycopeptide antibiotic by adding any N-acetyl-D-amino acids (i.e., NAC, N-acetyl-Alanine, N-acetyl glycine, etc.) years prior to the filing of the instant application (see, e.g., US’385 at ¶¶[0020]-[0022], [0036], [0141]-[0144]). Accordingly, US’385 provides the closest relevant teachings to the claimed invention, and US’385 directs artisans to practice the same invention with the predicted and expected result of stabilizing glycopeptide antibiotics, exactly as currently claimed.
Third, there exists no evidence that “these inventors proved him wrong” (see, e.g., MPEP § 716.05), because US’385 was published years prior to the filing of the instant application, and the instant application obtained the exact results taught and suggested by US’385, namely that the addition of any N-acetyl-D-amino acids (i.e., NAC, N-acetyl-Alanine, N-acetyl glycine, etc.) to any glycopeptide antibiotic would result in stabilization of the glycopeptide antibiotic (see, e.g., US’385 at ¶¶[0020]-[0022], [0036], [0141]-[0144]). Accordingly, the instant inventors appear to have “proved US’385 correct” rather than “proved him wrong”.
Accordingly, the proffered evidence and arguments have been fully considered, but not found persuasive to establish the existence of skepticism of experts (see, e.g., MPEP § 716.05), because US’385 directly addresses the expected and predicted results, and US’385 is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)).
Accordingly, all proffered arguments and evidence have been fully considered, but such evidence is not commensurate in scope with the requirements of MPEP § 716.05, and therefore fail to establish inoperability of the prior art.
Unexpected Results
It is the Examiner’s understanding that the Declarant is alleging the existence of unexpected results commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02, wherein such results are sufficient to rebut prima facie obviousness (see, e.g., Dec. filed 7/29/2026 at ¶¶24-25, alleging “This is a surprising result”).
The requirements for establishing unexpected results is discussed at MPEP §716, §716.01, and §716.02. Specifically, to establish such unexpected results, the allegations must be timely and supported by objective evidence (see, e.g., 37 C.F.R. 1.132; see MPEP §§ 716.01, 716.01(a), 716.01(c)); to be of probative value the proffered evidence must be related to the claimed invention (see MPEP §§ 716.01(b), discussing nexus requirement and noting that "[w]here the offered secondary consideration actually results from something other than what is both claimed and novel in the claim, there is no nexus to the merits of the claimed invention"); the evidence must establish that the expected results occur to an unexpected extent (see, e.g., MPEP § 716.02(a)(I)), on the basis of statistically and practically significant evidence (see, e.g., MPEP § 716.02(b)(I)), which is fully explained (see, e.g., MPEP § 716.02(b)(II)), commensurate in scope with the claimed invention (see, e.g., MPEP § 716.02(d)), and wherein a comparison of the claimed invention with the closest prior art of record is provided (see, e.g., MPEP § 716.02(e)). Furthermore, even if evidence satisfying MPEP §§ 716.02, 716.02(a), 716.02(b), 716.02(d), and 716.02(e) is set forth on record, such evidence may not be sufficient to rebut prima facie obviousness because the evidence of expected and unexpected results must be weighed (see, e.g., MPEP § 716.02(c)(I)) and the totality of the record considered (see, e.g., MPEP §§ 716.01(d), 716.02(f)), including teachings in the prior art and evidence of expected results which weigh in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)).
Here, the proffered data is insufficient to establish unexpected results commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02, at least because
(i) the proffered data is of unknown statistical and practical significance in the absence of proper controls for each experimental condition and in the absence of any identified statistical test, indication of experimental variability, or p-value (see, e.g., MPEP § 716.02(b)(I), § 716.02(b)(II));
(ii) the proffered data is not commensurate in scope with the instantly claimed invention, as instant claims 5 and 13 read upon a vast and highly varied array of gases (e.g., 99% O2 + 1% “air”, 99.9% argon + 0.1% “air”, etc.) , mixtures of glycopeptide antibiotics, pH ranges of 1-14 (see instant claim 1), temperature ranges of 0-50+ °C, etc., etc.; in addition, Declarant is directed to the definition and interpretation of “about” as set forth in the claim interpretation section above (see, e.g., MPEP § 716.02(d));
(iii) the proffered data does not unambiguously compare the claimed invention to the closest prior art, which appears to inherently and implicitly be made in atmospheric air and would be readily understood to inherently contain a headspace (see, e.g., US’385 at examples; see, e.g., MPEP § 716.02(e)); and
(iv) the proffered data appears to show the exact result taught, predicted, and expected in view of US’385, namely that glycopeptide antibiotics are stabilized in the presence of any N-acetyl-D-amino acid (see, e.g., US’385 at ¶¶[0020]-[0022], [0036], [0141]-[0144]), and data confirming the expected results taught by the prior art weighs in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)).
Accordingly, no evidence of unexpected results commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02 have been identified or placed on record at this time, and the only proffered evidence of record is of unknown statistical significance but appears to show the exact result taught and expected in view of the US’385 disclosure. Critically, evidence showing that the predicted and expected results identified by the prior art cannot reasonably be said to be “surprising” or “unexpected”.
Accordingly, all proffered arguments and evidence have been fully considered, but such evidence is not commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02, and therefore fail to establish unexpected results.
Additional Considerations
It is the Examiner’s understanding that Declarant is alleging that the amended claim scope is patentable because US’385 is silent regarding headspace containing an air-containing gas (see, e.g., Dec. filed 7/29/2026 at ¶¶7-10, 16-17, 23-25).
“Silence” does not mean that a parameter is not inherently present or necessarily implied. As acknowledged by the Declarant
The examples in US'385 describe solutions being "filled into vials, stoppered and stored for 4 weeks at 25±2°C/60±5% RH" (paragraph [0211]), but do not specify the headspace atmosphere.
(see, e.g., Dec. filed 7/29/2026 at ¶16).
Accordingly, Declarant acknowledges that a headspace atmosphere would inherently exist, but that US’385 does “not specify the headspace atmosphere” (see id). In the absence of clarification regarding the headspace atmosphere, Declarant is directed to MPEP § 2112.01, which explains that
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990)
Here, in view of the silence regarding the headspace atmosphere, one of ordinary skill in the art would not unreasonably assume or import any special limitations into the US’385 disclosure, and would readily conclude that the specific headspace atmosphere was not of critical importance, and that any headspace atmosphere would be within the scope of the disclosed invention (i.e., null hypothesis that the headspace atmosphere was not critical). Critically, any level of “air” would satisfy the requirements of the independent claim. This is relevant because the normal and routine procedures in the pharmaceutical packaging arts included using sterile atmospheric air in pharmaceutical packaging (see, e.g., US’385 at ¶¶[0035], [0079], [0205]-[0206], noting that US’385 expressly directs artisans to pack resulting compositions in “ready to use” containers and kits comprising containers holding solutions of the invention). In the complete absence of any guidance requiring a specialized headspace atmosphere, artisans would reasonably practice the invention of US’385 using routine and cost-effective pharmaceutical packaging techniques in the art:
Pharmaceutical containers are well-understood by artisans to routinely contain a headspace (see, e.g., Duncan at title, abs, 230-231 at bridging ¶);
It is well-understood that a headspace may comprise “atmospheric air” or “sterile air” (see, e.g., Duncan at 236 at col II at § Chemical Oxidation of the TSB; 234-235 at bridging ¶);
It is well-understood that “atmospheric air” contains oxygen (see, e.g., Duncan at 236 at col II at § Chemical Oxidation of the TSB);
An artisan would readily appreciate that when oxygen in a headspace is derived from “atmospheric air”, although it would initially be expected to be approximately 20.9% atm (see id. at 236 at col II), that this number would be high because moisture/water would lower the measured percentage, and therefore the measured level of O2 would be measured lower than 20.9 % atm, such as 19.8% atm or even 17.9% atm (see id. at 238-239 at bridging ¶, Figures 1-7 at time zero); and
An artisan would readily appreciate that measurements of O2 content in the headspace of pharmaceutical containers was routine in the prior art, and used for quality control and detection of contamination (see, e.g., Duncan at title, abs, 230-231 at bridging ¶).
Therefore, the silence of US’385 would not direct an artisan to utilize a specialized atmosphere in the headspace of packages, but rather would reasonably direct artisans to utilize routine pharmaceutical packaging processes, which would include sterile atmospheric air in the headspace of such containers, wherein the headspace would be expected and predicted to contain atmospheric oxygen at approximately 17.9% atm to 20.9 % atm (see, e.g., Duncan at 238 at Fig. 1-4, 239 at 5-7, 238 at col. I at 1st full ¶ to 239 at 1st partial ¶).
Accordingly, all proffered arguments and evidence pertaining to patentability have been fully considered, but such arguments and evidence are insufficient to rebut prima facie obviousness in view of the new rejections of record, which were necessitated by Applicant amendment.
General Dismissal of US2017/0348385A1
Upon review, it is the Examiner’s understanding that Declarant’s positions and arguments are substantially premised upon simply dismissing or ignoring the express teachings of US’385 (see, e.g., Dec. filed 7/29/2026, passim, suggesting that N-acetyl-D-cysteine and N-acetyl-D-alanine would not be considered functional equivalents by artisans). Such premise is not tenable because US’385 expressly informs artisans to make and use aqueous compositions with any glycopeptide antibiotic and any N-modified-D-amino acid (see, e.g., US’385 at ¶¶[0141]-[0144]), and US’385 explicitly teaches and directs artisans to methods for stabilizing glycopeptide antibiotics using any “N-acetyl-D-amino acid” without limit:
[0036 ] The present invention further provides a method for stabilizing glycopeptide antibiotics which involves addition of N-acetyl-D-amino acids to a solution comprising a glycopeptide antibiotic or addition of a glycopeptide antibiotic to a solution comprising N-acetyl-D-amino acids.
(see, e.g., US’385 at ¶[0036]).
Wherein “N-acetyl-D-amino acids” is a term explicitly defined to include any amino acids (see, e.g., US’385 at ¶¶[0071]-[0072]), including “D-Cysteine” (see, e.g., US’385 at ¶¶[0066], [0068]). Accordingly, US’385 clearly sets forth predicted and expected results that the exemplified embodiments apply to all “N-acetyl-amino acids”, wherein all “N-acetyl-amino acids” would stabilize vancomycin relative to N-acetylated di- and tri-peptides (see, e.g., US’385 at ¶[0227]), and wherein all such compositions, using any N-acetyl-D-amino acid, would be predicted and expected to be usable as a medicament for use in treating bacterial infections (see, e.g., US’385 at ¶¶[0020]-[0022], [0036]). This is pertinent because US’385 is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)), and US’385 does more than “suggest” the use of N-acetyl-D-amino acids such as NAC, but instead expressly teaches such methods and combinations.
Accordingly, all arguments proffered by Declarant alleging differences between N-acetyl-D-cysteine and N-acetyl-D-alanine (see, e.g., Dec. filed 7/29/2026, passim) are understood to rest upon the premise that the prior art is inoperative, would be met by skepticism of experts, or otherwise that the substitution of one N-acetyl-D-amino acid for another would yield unexpected results (see, e.g., Dec. filed 7/29/2026, passim). Each of these interpretations have been addressed above, and not found persuasive for reasons of record.
Accordingly, all arguments proffered by Declarant premised upon the assumption that a reasonable artisan would ignore, dismiss, or be unaware of US’385 have been fully considered but not found persuasive because, per MPEP § 2141.03, “The person of ordinary skill in the art is a hypothetical person who is presumed to have known the relevant art at the relevant time” (see, e.g., MPEP § 2141.03(I)). Here, US’385 expressly informs artisans to make and use aqueous compositions with any glycopeptide antibiotic and any N-modified-D-amino acid (see, e.g., US’385 at ¶¶[0141]-[0144]), and US’385 explicitly teaches and directs artisans to methods for stabilizing glycopeptide antibiotics using any “N-acetyl-D-amino acid” without limit (see, e.g., US’385 at ¶[0036]).
Accordingly, all arguments premised upon the assumption that a reasonable artisan would dismiss or ignore the full disclosure of US’385 is not persuasive because US’385 is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)).
Weighing Objective Evidence
Per MPEP § 716.01(d), the ultimate determination of patentability must be based on consideration of the entire record and notes that submission of evidence of patentability does not mandate a conclusion of patentability in and of itself. Accordingly, the Declaration has been fully considered but is not found persuasive because it does not establish unexpected results, inoperability of the prior art, skepticism of experts, or patentability of the amended claim scope as explained above. Therefore, in view of the record as a whole, the Declaration is insufficient to overcome the rejections of record, which are maintained as set forth above.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
WO2016/071495A116 (12 May 2016) pertains to solutions of glycopeptides, including vancomycin, comprising an amino acid derivative such as N-acetyl-Glycine or N-acetyl-D-Alanine, wherein the solutions are rendered stable or stabilized for long-term periods (see, e.g., WO’495 at title, abs, 5 at lines 15-25), wherein the compositions may have a pH of about 3-6 or about 4.0 to 5.5 (see, e.g., WO’495 at 4 at lines 24-31).
WO 2014/194296 Al17 (4 December 2014; cited in IDS filed 5/19/2023) pertains to vancomycin compositions having a pH of about 3 to 8, and exhibiting stability for at least about 12 months (see, e.g., WO’296 at title, abs, claims 1-2, 4-6).
WO2016/12708718 (11 August 2016) pertains to aqueous vancomycin compositions (see, e.g., WO’087 at title, abs, claims), wherein the compositions comprise amino acids or amino acid derivatives (see, e.g., id. at ¶[0008], claims).
WO2020/208093A119 (15 October 2020) pertains to cysteine derivatives for use in the treatment and prevention of bacterial infections (see, e.g., WO’093 at title, abs, claims).
US2018/0133286A120 (17 May 2018) pertains to solutions of glycopeptides, including vancomycin, comprising an amino acid derivative such as N-acetyl-Glycine or N-acetyl-D-Alanine, wherein the solutions are rendered stable or stabilized for long-term periods (see, e.g., US’286 at title, abs, ¶[0037]), wherein the compositions may have a pH of about 3-6 or about 4.0 to 5.5 (see, e.g., US’286 at ¶¶[0029]-[0030]]).
EP2520282A221 discloses that reduced oxygen content in vancomycin formulations is desirable (see, e.g., EP’282 at claims, abs, ¶¶[0001]-[0004], [0009]-[0010]).
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 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 RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
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.
/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 See, e.g., Requirement mailed 12/04/2025 at 6 at 1st ¶, noting that Applicant should identify claims readable on the elected species “including any claims subsequently added”.
2 See, e.g., Spec. filed 5/19/2023 at 3 at final ¶; see also PG PUB US 2024/0000884 A1 at abs, ¶[0019], claim 2.
3 Wenger et al., Frequently asked questions in hypoxia research. Hypoxia (Auckl). 2015 Sep 18;3:35-43. doi: 10.2147/HP.S92198. PMID: 27774480; PMCID: PMC5045069; see Wenger et al. at abs, 35-36 at bridging ¶, 36 at § Why must humidity be considered?, 37 at Fig. 1, showing that “dry” air at 20.9% O2 is actually lower (e.g., 18.6%) when accounting for gaseous water and other components.
4 See, e.g., Wenger et al. at abs, 35-36 at bridging ¶, 36 at § Why must humidity be considered?, 37 at Fig. 1, showing that “dry” air at 20.9% O2 is actually lower (e.g., 18.6%) when accounting for gaseous water and other components.
5 Sithersingh, Michael. Determination of Polar Solvents by Static Headspace Extraction – Gas Chromatography (SHE-GC). 2018. Seton Hall University, PhD dissertation. Seton Hall University Dissertations and Theses.
6 Wenger et al., Frequently asked questions in hypoxia research. Hypoxia (Auckl). 2015 Sep 18;3:35-43. doi: 10.2147/HP.S92198. PMID: 27774480; PMCID: PMC5045069
7 Brueckner et al., Tunable diode laser absorption spectroscopy as method of choice for non-invasive and automated detection of microbial growth in media fills. Talanta. 2017 May 15;167:21-29. doi: 10.1016/j.talanta.2017.01.088. Epub 2017 Jan 31. PMID: 28340713.
8 See, e.g., Spec. filed 5/19/2023 at 3 at final ¶; see also PG PUB US 2024/0000884 A1 at abs, ¶[0019], claim 2.
9 See, e.g., Spec. filed 5/19/2023 at 3 at final ¶, 10-11 at bridging ¶, referring to “normal atmosphere” and “filled under atmospheric conditions”, reporting an O2 target with two significant digits.
10 Wenger et al., Frequently asked questions in hypoxia research. Hypoxia (Auckl). 2015 Sep 18;3:35-43. doi: 10.2147/HP.S92198. PMID: 27774480; PMCID: PMC5045069; see Wenger et al. at abs, 35-36 at bridging ¶, 36 at § Why must humidity be considered?, 37 at Fig. 1, showing that “dry” air at 20.9% O2 is actually lower (e.g., 18.6%) when accounting for gaseous water and other components.
11 Duncan et al., The Application of Noninvasive Headspace Analysis to Media Fill Inspection. PDA J Pharm Sci Technol. 2016 May-Jun;70(3):230-47. doi: 10.5731/pdajpst.2015.006312. Epub 2016 Feb 9. PMID: 26865678.
12 E.g., 1% w/V = 1 gram per 100 mL, or 1000 mg per 100 mL, which is 10 mg/mL.
13 E.g., 1% w/V = 1 gram per 100 mL, or 1000 mg per 100 mL, which is 10 mg/mL.
14 E.g., N-acetyl-D-Cys (NAC) has a MW of ~163.19g/mol and Vancomycin has a MW of ~1485.70 g/mol, and the minimum (i.e., 0.5:1 molar ratio of 0.5 % w/V vancomycin) would be half of 0.00345 mmol/mL, or 0.281 mg/mL of NAC; and the maximum (i.e., 40:1 molar ratio of 15 % w/V vancomycin) would be 40 times 0.1035 mmol/mL or 675.60 mg/mL NAC.
15 E.g., N-acetyl-D-Cys (NAC) has a MW of ~163.19g/mol and Vancomycin has a MW of ~1485.70 g/mol, and the minimum (i.e., 0.5:1 molar ratio of 0.5 % w/V vancomycin) would be half of 0.00345 mmol/mL, or 0.281 mg/mL of NAC; and the maximum (i.e., 40:1 molar ratio of 0.5 % w/V vancomycin) would be 40 times 0.00345 mmol/mL or 22.52 mg/mL NAC.
16 Cited in previous action.
17 Cited in previous action.
18 Cited in previous action.
19 Cited in previous action.
20 Cited in previous action.
21 Cited in previous action.
