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 . 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.
Election/Restrictions
Applicant's election with traverse of group I (polypeptides) and SEQ ID 2 in the reply filed on 26 Nov, 2025 is acknowledged. The traversal is on the ground(s) that 37 CFR 1.475 (b) does not state that they are limited to one method group, and groups III-VI are method claims that should be rejoined. This is not found persuasive because the regulation states that unity of invention is limited to only some combinations of product, method of making, method of using, and apparatus, and multiple methods of using does not fit any of those groups.
The requirement is still deemed proper and is therefore made FINAL.
Applicants have elected a formulation of SEQ ID 2. A search was conducted for this invention, and it was determined to lack patent eligibility. As a result, claims 1-10, 14, and 15 were examined and claims 11-13, 16, 17, and 19-26 were withdrawn from consideration. Applicants have stated that they believe their election reads on claims 16, 17, 25, and 26, but those claims describe unelected features of the formulation, and so are properly withdrawn.
During examination, a reference was found that anticipated at least one non-elected species. This reference is discussed below.
Claims Status
Claims 1-17 and 19-26 are pending.
Claims 11-13, 16, 17, and 19-26 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 26 Nov, 2025.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-10, 14, and 15 are rejected under 35 U.S.C. 101 because they read on a judicial exception (natural phenomenon).
The Supreme Court has given a three part test for patent eligibility under this statute:
1) Is the invention drawn to a process, machine, manufacture, or composition of matter?
2a) If the invention passes the first test, does a judicial exception apply?
2b) If a judicial exception applies, is there something beyond the judicial exception?
Applying the test
The claims are drawn to peptides, which are compositions of matter.
2a) Claim 2 requires that the peptides be of vegetable origin, which is defined as the sequence can be isolated from plants, i.e. that the sequence is produced by a plant. This is a natural product, a judicial exception as a natural phenomenon. Note that applicants have stated that SEQ ID 2, applicant’s elected species, reads on this claim. Alternatively, Steinberg et al (Antimicrob. Agents Chemother. (1997) 41(8) p1738-1742) describes protegrin 1 (title), and antimicrobial isolated from pigs (abstract) with the sequence RGGRLCYCRRRFCVCVGR (p1738, 2nd column, 2nd paragraph). Note that this is an antimicrobial sequence with 18 AAs, 6 Arg residues and no other charged residues (6/18=0.33), and one Tyr and one Phe residue (both aromatic, 2/18=0.11) which has activity against gram negative bacteria, such as E. coli and MRSA (table 2, p1740, top of page). Claims 14 and 15 are product by process claims, which do not add any structure to the claim limitations. This means that every claim reads on applicant’s elected species, which they state is a plant protein, and most of them read on protegrin 1, produced naturally by pigs.
2b) The claims can be met with just the polypeptide; this means that there are embodiments that have nothing beyond the sequence. Thus, the claims lack patent eligibility under this statute.
Claim Rejections - 35 USC § 112(a)
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.
Claims 1-10, 14, and 15 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.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient" (MPEP 2163).
A claimed genus may be satisfied through sufficient description of a representative number of species or disclosure of relevant, identifying characteristics such as functional characteristics coupled with a known or disclosed correlation between function and structure(MPEP 2163(3)a(II)). The number of species that describe the genus must be adequate to describe the entire genus; if there is substantial variability, a large number of species must be described.
The analysis for adequate written description considers (a) actual reduction to practice, (b) disclosure of drawings or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure and (d) representative number of samples.
The issue is that a person of skill in the art would not know what sequences that meet the structural limitations of the claims are antimicrobial.
(a and b) actual reduction to practice and disclosure of drawings or structural chemical formulas: Applicants are claiming polypeptides comprising a segment of 18-27 AAs, which are 30-40% positively charged amino acids (defined as Arg, Lys, and His), 9-14% aromatic amino acids (defined as Phe, Tyr, and Trp), with no negatively charged amino acids (defined as Asp and Glu). Dependent claims have narrower ranges, and additional requirements with respect to hydrophobicity, charge, and isoelectric point. SEQ IDs 1-4 are given as examples.
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure: Applicants are claiming antimicrobial cationic peptides with some aromatic amino acids. The claims have a functional requirement that the peptides be antimicrobial. However, applicants have not disclosed what structural requirements are necessary for a sequence to be antimicrobial. A person of skill in the art would not know what sequence/hydrophobicity/charge requirements are necessary to meet this functional requirement. In essence, applicants have described their invention by function. This is not sufficient to meet the written description requirement.
As of applicant’s priority date, it was not possible to predict if a given molecule bound to a receptor. Lowe (blog “In the pipeline” entry of 7 Sept, 2022) describes an experiment where that was attempted. 39K compounds, including known antibiotics, were screened against E. coli for growth inhibition, finding 218 active compounds (1st page, 3d paragraph). These were computer docked to a set of 296 essential bacterial proteins by multiple docking procedures (1st page, 3d paragraph), along with 100 random inactive compounds (2nd page, 1st paragraph). The number of strong binders predicted were essentially the same between the active compounds and the controls, and out of 142 compound/target interactions previously known, the methodology found only 3 (2nd page, 2nd paragraph). While a given docking program may accurately predict if compound A binds to protein B, it is impossible to a priori know if the prediction is accurate. In other words, several years after applicant’s priority date, it was not possible to predict if a given compound and target bound to each other.
Nor is it possible to modify known sequences to reliably find new compounds. Guo et al (PNAS (2004) 101(25) p9205-9210) looked at the effect of random mutations (title). In a DNA repair enzyme, about one mutation in three killed the activity of the protein, consistent with studies with other proteins (abstract). Yampolsky et al (Genetics (2006) 170 p1459-1472), using a different methodology, found that even conservative substitutions were prone to problems (table 3, p1465, top of page). In other words, unless there is some information known about the binding, mutating the sequence is likely to be detrimental, making it a poor way to generate new compounds.
There are sequences that meet applicant’s criteria that are not known as antimicrobial. Human cytochrome C (NCBI sequence NP 061820 (2025)) has a segment (residues 72-89) which has 6 positively charged residues (33%) and 2 aromatic residues (11%) and no negatively charged amino acids over 18 amino acids. This is an electron transport protein (2nd page, “comment”), rather than an antimicrobial sequence.
Buccini et al (Front. Cell. Infection Microbiol. (2021) 10 article 612931) states that cell penetrating sequences are antimicrobial (2nd page, 1st column, 3d paragraph, continues to 2nd column), with direct antibacterial activity (2nd page, 2nd column, 2nd paragraph). However, Mitchell et al (J. Peptide Res. (2000) 56 p318-325) shows that RRRRRRR sequences are cell penetrating peptides, but the Lys, His, and Ornithine analogs are not (fig 1, p321, top of page, and fig 3, p322, 1st column, top of page). Similar to Yampolsky et al, this strongly suggests that even conservatively substituted variants of antimicrobial peptides are likely to have greatly different antimicrobial properties.
If applicants are relying upon their claimed charge distribution, it should be noted that not all the amino acids in their groupings have equivalent charge. The table of acid/base characteristics of amino acids kept by Vanderbilt university (downloaded Dec, 2025) states that the side chains of His and Cys have pKas of 6.04 and 8.37 respectively. This means that, at physiological pH, His has only a partial positive charge, while Cys has a partial negative charge, on average.
(d) representative number of samples: Applicants have listed 4 sequences, most of which have fairly disappointing activity (table p14, top of page). These sequences have no real identity with each other, nor is there any requirement for identity for the broader claims (although claim 7 describes sequences with at least 80% identity to these four disclosed peptides). However, with no information as to what parts of these sequences are responsible for the activity they have, evidence that the charge and aromaticity requirements are not sufficient to yield an antimicrobial sequence, and that even conservative mutations are likely to abrogate activity, applicants do not have written description for their claims.
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.
first rejection
Claims 1-10, 14, and 15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1, and claims dependent on it, require that the sequence be antimicrobial. However, applicants have not defined the test that determines if a given sequence is antimicrobial or not. A test at high concentration on a relatively easy to kill gram positive bacterium is likely to give different results than a different result than the same sequence at low concentrations against a difficult to kill gram negative bacterium.
second rejection
Claims 4 and 7 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.
Claims 4 and 7 require a Boman index between 2 and 4, a net positive charge between 5.5 and 8, and a hydrophobicity between 0 and -1. The calculation for the Boman index is the average solubility of the amino acids in the sequence (p16, 7th paragraph, continues to p17, 1st paragraph). However, the solubility of each amino acid is not defined. Applicants point to Boman (J. Int. Med (2003) 254 p197-215) and point to table 2 to define this, but that table is merely a list of antimicrobial peptides, with columns for number of amino acids, net charge, % basic amino acids, and “index,” which is presumably what applicants are discussing. However, it describes the index as the average free energy difference when the side chains move from cyclohexane to water (table 2, p202, 2nd column, top of page)
PNG
media_image1.png
404
350
media_image1.png
Greyscale
. This is not consistent with applicant’s statement of solubilities. It should be noted that the solubility of an amino acid is a function of pH and ionic strength, among other parameters. Net charge is defined in terms of the pH (p16, 6th paragraph), but the pH of the solution is not defined by the claim. Hydrophobicity is defined as the average hydrophobicity of the amino acids that make up the sequence (p17, 4th paragraph), but the hydrophobicities of individual amino acids are not defined. A hydrophobicity scale is mentioned (p7, 7th paragraph), but it is clear from the language that this is not the only scale, nor is hydrophobicity defined in terms of this scale. In other words, these claims require parameters that are either not defined by applicants, or are based on variables not defined by applicants.
Claim Rejections – 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection I, a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 5 and 6 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 1, from which claims 5 and 6 depend, require antibacterial sequences. Claim 5 is met if the sequences are antibacterial, so the claim does not further limit. Claim 6 requires activity to gram negative and/or gram positive bacteria. This is all bacteria, so the claim also does not further limit. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Improper Markush
Claims 1-10, 14, and 15 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of claims 1, 7, and 15 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: there is no core structure or sequence. The limitations of claim 1 have no core structure, so there is no sequence. The sequences of claims 7 and 15 have no real identity with SEQ ID 2 (applicant’s elected species). Nor do they fall into any art recognized structural class that leads to antimicrobial activity.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 3, 5, 6, 8-10, and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Steinberg et al (Antimicrob. Agents. Chemother. (1997) 41(8) p1738-1742). Please note that this reference does not read on applicant’s elected species.
Steinburg et al discuss protegrin-1, an antimicrobial peptide (title) with the sequence RGGRLCYCRRRFCVCVGR-NH2 (p1738, 2nd column, 2nd paragraph). The sequence had activity against E. coli and MRSA (an antibiotic resistant bacterium).
This sequence has no negatively charged amino acids, 2 aromatic amino acids (11%), and 6 positively charged amino acids (33%) out of 18 total, with antimicrobial activity. Thus, the reference anticipates claims 1, 3, 5, and 6.
Steinburg et al shows activity against E coli, anticipating claim 8.
While Steinburg et al has not shown it, the sequence has every property applicants have stated is required to be active against other bacteria, and was demonstrated to have activity against at least one antibiotic resistant bacterium. This, it will inherently meet the limitations of claims 9 and 10.
Claim 14 has a product by process requirement that the sequence be discovered using the screening methodology of claim 11. However, that gives no other structural limitations to the sequence. The MPEP states that “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (MPEP 2113). Thus, this sequence anticipates claim 14.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
Examiner interviews are available via telephone 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, Melissa Fisher can be reached at 571-270-7430. 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.
/FRED H REYNOLDS/Primary Examiner, Art Unit 1658