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 .
DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions. Response to Election/Restriction filed on July 22, 2026 is acknowledged. Claims 17-26 are pending in the current application.
Election/Restrictions
Applicant elected without traverse SEQ ID NO:5 from List I and Staph from List II in the reply filed July 22, 2026.
After further review, the election of species is withdrawn. Claims 17-26 are examined on the merits of this office action.
Sequence Compliance
This application fails to comply with the requirements of 37 C.F.R 1.821-1.825 for the reasons set forth on the attached Notice to Comply With Requirements For Patent Applications Containing Nucleotide Sequence And/or Amino Acid Sequence Disclosures. Applicant must comply with the requirements of the sequence rules (37 CFR 1.821-1.825) before the application can be examined under 35 U.S.C 131 and 132. Each sequence disclosed must appear separately in the “Sequence Listing.” Each sequence set forth in the “Sequence Listing” must be assigned a separate sequence identifier. Applicant failed provide sequence identifiers for all sequences listed in claims. For example, the peptide of formula I requires a sequence listing and SEQ ID NO.
Specification Objection
The specification is objected to for containing referring to sequences without also identifying them by the sequence identifier assigned to them in the sequence listing as required by 37 CFR 1.821(d). The specification discloses peptide sequences, and these are missing their respective sequence identifiers. For example, General Formula I on page 6 is missing its sequence identifier. The examiner would like to bring the applicant’s attention to the following excerpt from MPEP §2422.03:
37 CFR 1.821(d) requires the use of the assigned sequence identifier in all instances where the description or claims of a patent application discuss sequences regardless of whether a given sequence is also embedded in the text of the description or claims of an application. This requirement is also intended to permit references, in both the description and claims, to sequences set forth in the "Sequence Listing" by the use of assigned sequence identifiers without repeating the sequence in the text of the description or claims. Sequence identifiers can also be used to discuss and/or claim parts or fragments of a properly presented sequence. For example, language such as "residues 14 to 243 of SEQ ID NO:23" is permissible and the fragment need not be separately presented in the "Sequence Listing." Where a sequence is embedded in the text of an application, it must be presented in a manner that complies with the requirements of the sequence rules.
The proper way to reference a peptide sequence is for example, GPX1RRYX2RR(SEQ ID NO: X) (see 37 CFR 1.821(d)). This error should be corrected throughout the Applicant’s specification.
Claim Objections
Claim 17 is objected to for minor informalities, it is suggested that claim 17 be amended as follows: the “e” following tryptophan in lines 8 and 10 should be removed.
Furthermore, the peptide sequence is missing the sequence identifier. The proper way to claim a peptide sequence is for example, GPX1RRYX2RR (SEQ ID NO: X) (see 37 CFR 1.821(d)). This error should be corrected.
Furthermore, the last three lines of claim 17 should be amended as follows: “wherein X1 is an amino acid selected from the group consisting of glycine (G) and tryptophan[[e]] (W), and X2 is an amino acid selected from the group consisting of cysteine (C), alanine (A), and tryptophan[[e]] (W)”.
Claim 18 is objected to for the following informality: Applicant should amend claim 18 as follows: “The method according to claim 17, wherein the subject is in need of antimicrobial activity against the Escherichia genus or the Staphylococcus genus.”
Claim 19 is objected to for the following informality: Applicant should amend claim 19 as follows: “The method according to claim 17, wherein the subject is in need of antifungal activity against…”
Claim 20 is objected for the following informality: claim 20 should be amended as follows: “The method according to claim 17, wherein X2 is anamino acid selected from the group consisting of C and W.
Claim Rejections – 35 USC § 112, first paragraph
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 17-26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating specific bacterial/fungal infections with specific peptides, does not reasonably provide enablement for treatment of all microbial infections, which includes bacterial, viral infections and fungal infections. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To comply with the enablement requirements of 35 U.S.C. §112, first paragraph, a specification must adequately teach how to make and how to use a claimed invention throughout its scope, without undue experimentation. Plant Genetic Systems N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003). There are a variety of factors which may be considered in determining whether a disclosure would require undue experimentation. These factors include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The Nature of the Invention/ The breadth of the claims
The breadth of the claims is not commensurate with the scope of the enabling disclosure. Claim 17 broadly encompasses methods of providing antimicrobial and or antifungal activity by administering a peptide within the scope of Formula I to a subject in need thereof. The claims further encompass treatment of subjects requiring antimicrobial activity against any bacteria or fungi. However, the specification demonstrates biological activity for only selected peptide embodiments while simultaneously demonstrating that numerous disclosed peptide variants exhibit substantially reduced or poor activity against tested bacterial and fungal species.
The claimed invention relates to biologically active antimicrobial peptides for providing antimicrobial and/or antifungal activity in a subject. Biological activity of AMPs depends upon numerous factors, including amino acid sequence, peptide conformation, charge, hydrophobicity, interactions with microbial membranes, and microorganism specific susceptibility. Because relatively minor sequence modifications can substantially alter biological activity, peptide function cannot be reliably predicted from sequence similarity alone.
The State of the Prior Art and the predictability or unpredictability of the art
Applicant’s specification fails to adequately describe treatment of any bacterial/fungal infection.
At the time of the filing, AMPs and methods for measuring activity were generally known in the art. However, it was recognized that small amino acid substitutions frequently results in substantial change in activity , toxicity and potency. Thevissen (cited in Applicant’s IDS) disclose Ib-AMP1 and AMP4 which comprise peptides of the instant claims (Table 1) but are larger peptides. The activity of these larger peptides appears to be substantially greater to the instant peptides (see Table 2). The antimicrobial peptide art is highly unpredictable with respect to biological activity. The Applicants own experimental data demonstrates that closely related peptide variants exhibit markedly different antimicrobial and antifungal activities. For example, several disclosed peptide variants exhibit MIC values greater than 100 ug/ml against tested bacterial species, whereas VESCA3 and VESCA-OH demonstrate substantially greater activity against selected microorganisms. The specification therefore illustrates that relatively small sequence modifications produce significant and unpredictable differences in biological function. These results evidence that the activity cannot be reliably extrapolated across any bacterial or fungal species.
The Relative Skill of Those in the Art
One of ordinary skill in the art would have possessed routine techniques for peptide synthesis, purification, and antimicrobial susceptibility testing, including determination of MICs. However, such routine techniques to don’t eliminate the need for testing to determine whether a particular peptide variant possesses the claimed antimicrobial and or antifungal activity. Rather the skill artisan would still be required to synthesize each candidate peptide and experimentally evaluate its biological activity because the specification does not provide sufficient predictive guidance for identifying active peptides.
Amount of Guidance/ The Presence or Absence of Working Examples
Although the specification contains working examples, the examples are limited to only certain peptide embodiments and do not demonstrate that the full scope of the claimed genus possesses the claimed biological activity. The experimental data reported in Table 2 demonstrate considerable variability among closely related peptide variants. For example, Ib-AMP4 exhibits MIC values greater than 100 ug/ml against E.Coli, Staph Aureus, and cutibacterium acnes. Likewise, VESCA-NH2, VESCA-NH4, VESCA1, and VESCA2 exhibit MIC values greater than 100 ug/ml aginst one or more bacterial tested. In contrast, only selected embodiments, such as VESCA3 and VESCA-OH3, demonstrate substantially improved antimicrobial activity. Similarly, antifungal activity varies among the disclosed peptides, with VESCA3 identified as having the best antifungal activity and subsequently selected for further cytotoxicity evaluation. Thus, the working examples demonstrate activity for only a limited subset of embodiments and further demonstrate that biological activity is highly dependent upon the particular peptide sequence.
The Quantity of Experimentation Necessary
Considering the factors above, the skilled artisan would be burdened with undue experimentation in determining if composition of the instant invention would be effective as an antimicrobial against all microbes (bacteria, viral, fungal). As such, the claims do not satisfy the enablement requirement of 35 U.S.C. 112 (a).
Therefore, in view of the Wands factors, the claims appear to require undue experimentation to use the full scope of the claimed invention.
Closest Prior Art Made of Record
McDaniel (WO2005007758). McDaniel teaches a peptide comprising instant SEQ ID NO:3 (claim 187, SEQ ID NO:146, Impatiens balsamina Ib-AMP4). However the peptide comprising SEQ ID NO:3 is embedded in a larger sequence (18mer). There is not teaching, suggestion or motivation to truncate this sequence to result in a peptide consisting of Formula I and SEQ ID Nos:3-5 and use the peptide in a subject in need of antimicrobial activity.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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 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.
/ERINNE R DABKOWSKI/Primary Examiner, Art Unit 1654
Prosecution Insights