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 .
Status of the Application
The election and amendment of 29 December 2025 are entered.
Claims 3, 4, 9, 10, 12, 13, 16-33, 35-53, 57-59, 62, 65-69, 71, and 73-142 have been canceled. Claims 1, 2, 5-8, 11, 14, 15, 34, 54-56, 60, 61, 63, 64, 70, and 72 are pending. Claims 5, 7, 14, 15, 60, 61, 63, 64, 70, and 72 are withdrawn with traverse. Claims 1, 2, 6, 8, 11, 34, and 54-56 are being examined on the merits.
Election/Restrictions
Applicant's election with traverse of Group I and SEQ ID NO: 1 in the reply filed on 29 December 2025 is acknowledged. The traversal is on the ground(s) that unity of invention exists because the same technical features are shared between the two groups The Applicants also argue that the peptides have a common property and activity in beta lactamase inhibition and antibacterial activity. The Applicants argue these are recognized class of beta lactamase inhibitory peptides that share the same or corresponding special technical features. The Applicants argue strategically position hydrophobic and charged amino acids to contribute to the shared mechanism. The Applicants argue this satisfies the unity of invention requirement.
This is not found persuasive because while the groups share the same technical feature, as indicated previously the requirement of PCT Rule 13.2 is not met when a Markush grouping does not contain alternatives of a similar nature having a common property or activity AND a common structure or a recognized class. The alternatives do not share a common structure, as there is a single position in each of SEQ ID NOs:1-4 that is invariant. The class of beta lactamase inhibitory peptides are such that they only group based on function rather than any specific structure. As noted below, the alternatives for each of SEQ ID NOs:1-4 range from ~3 million to 1.28 billion species considering only those positions that allow for any naturally occurring amino acid to be present. There is no clear evidence from the specification that every member of these genera is linked by a common property or activity. As further evidenced in the Silva et al. art cited by the Applicants on the IDS of 10 August 2023, there is no core structure or feature that links any beta lactamase inhibitory peptides together other than their common target. The Examiner does not find the Applicants’ arguments persuasive to overcome the restriction requirement and lack of unity.
The requirement is still deemed proper and is therefore made FINAL.
Claims 5, 7, 14, 15, 60, 61, 63, 64, 70, and 72 are 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. The Applicant indicates SEQ ID NO: 1 as elected reads upon claims 5, 7, 14, and 15, but the Examiner notes that each of these claims are linked to SEQ ID NOs: 3 or 4, which are distinct and separate from SEQ ID NO: 1. For instance, the X2 and X2 positions in SEQ ID NO: 3 are broadened to be any standard amino acid as compared to Y/F or V/L/I as in SEQ ID NO: 1. Similarly, SEQ ID NO: 4 is a distinct scope where the X1, X2, X3, X4, and A residues of SEQ ID NO: 1 are narrower. Claims 5, 7, 14, and 15 directly limit SEQ ID NOs: 3 or 4, not SEQ ID NO: 1 as elected. Applicant timely traversed the restriction (election) requirement in the reply filed on 29 December 2025.
SEQ ID NO: 1 has been searched in the prior art and rejections made below. During the search overlapping art reading upon SEQ ID NO:2 was also discovered. In the interests of compact prosecution rejections are provided below regarding SEQ ID NO: 2. No substantive search has been made of non-elected SEQ ID NOs: 3 or 4.
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 Objections
Claim 1 is objected to because of the following informalities: a space is missing between ID and NO in line 7. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 6, 8, 11, 34, and 54-56 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.
At issue for the claims is the highly generic nature of the claimed sequences. While SEQ ID NOs: 3-4 were not searched for prior art due to their non-election with traverse, the Examiner is considering them for the purposes of written description in the interests of compact prosecution. As claimed, the sequences are as follows:
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. In each there are multiple positions that can take the form of any amino acid. In SEQ ID NO: 1, this results in 64 million possible permutations not considering X1, X2, X3, or X4. In SEQ ID NO: 2, this results in an identical number of permutations before considering X5, X6, and X7. In SEQ ID NO: 3 there are 3.2 million possible permutations before considering X8, X9, X10, and X11. Finally, in SEQ ID NO: 4 there are 1.28e9 permutations before considering X12, X13, and X14.
The claims include the language that each peptide is “an antibacterial peptide” which implies function, as well as including the phrase that they each have “a binding motif”. Antibacterial activity implies both action against Gram positive and negative bacteria. Binding motif does not indicate any particular target, i.e. it could be binding to any protein, nucleotide sequence, carbohydrate, etc. These are functions with no clear structure-function nexus between any peptide having a generic motif as in SEQ ID NOs: 1-4 and the required antibacterial activity and binding capability.
The specification discloses a limited number of sequences reading upon each of SEQ ID NOs:1-4 in SEQ ID NOs: 5-8 and 64-80, where SEQ ID NOs: 64-80 represent one of SEQ ID NOs:5-8 fused to a cell penetrating peptide. SEQ ID NOs: 81-86 are also disclosed, however the Examiner is unable to match any sequence to the more generic motifs found in SEQ ID NOs: 1-4. Even if all of SEQ ID NOs: 5-8 and 81-86 are considered, at best there are a small handful of disclosed species as compared to the broad genera of 3 million to 1.28e9 species encompassed by SEQ ID NOs: 1-4.
There is no clear guidance how the semi-permanent positions of SEQ ID NOs: 1-4 necessarily leads to binding to any target let alone the ability of any species to serve as an antibacterial peptide. The Examples all target TEM-1 beta lactamase.
The prior art recognizes peptide-based beta lactamase inhibitors, for instance as discussed in Silva et al. Drugs of Today 54:737-746, published 2018 (cited on IDS of 10 August 2023). However, a limited number of peptides are disclosed by Silva as found in Table 1: HCRGHAAGDY, RRGHYY-NH2, CYHFLWGPC, CVHSPNREC, KKGEE, LLIILHAAGDYYAY, and a homodimer of Ac-CyβAR8VLR connected via a disulfide bridge. Notably, none of these fit within SEQ ID NOs:1-4 as claimed. The Silva peptides are all also such that there is no clear core structure of a peptide that reasonably leads it to being considered an antibacterial peptide targeting beta lactamase. Similarly, none are such that they expand upon the genus as already claimed and demonstrate that there was reasonable knowledge in the prior art that any of SEQ ID NOs: 1-4 necessarily had both a binding motif as well as serving as an antibacterial peptide.
The skilled artisan is essentially left with a single species from each genus. There is no indication that the single species are each representative of the full genus of claimed compounds having antibacterial activity and being able to bind to a site. The dependent claims narrow one or more positions but still leave from five to seven positions that are allowed to take the form of any standard amino acid, still allowing for millions to billions of potential species within each genus.
MPEP 2163 II. A. 3. (a) ii) states:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ( "[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) (Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in the record showing applicant conveyed that any other coating was suitable for a PTFE dental floss.) On the other hand, there may be situations where one species adequately supports a genus. See, e.g., Rasmussen, 650 F.2d at 1214, 211 USPQ at 326-27 (disclosure of a single method of adheringly applying one layer to another was sufficient to support a generic claim to "adheringly applying" because one skilled in the art reading the specification would understand that it is unimportant how the layers are adhered, so long as they are adhered); In re Herschler, 591 F.2d 693, 697, 200 USPQ 711, 714 (CCPA 1979) (disclosure of corticosteroid in DMSO sufficient to support claims drawn to a method of using a mixture of a "physiologically active steroid" and DMSO because "use of known chemical compounds in a manner auxiliary to the invention must have a corresponding written description only so specific as to lead one having ordinary skill in the art to that class of compounds. Occasionally, a functional recitation of those known compounds in the specification may be sufficient as that description."); In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 285 (CCPA 1973) (the phrase "air or other gas which is inert to the liquid" was sufficient to support a claim to "inert fluid media" because the description of the properties and functions of the air or other gas segmentizing medium would suggest to a person skilled in the art that appellant’s invention includes the use of "inert fluid" broadly.). See Juno, 10 F.4th 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) (where the claims are directed to species that bind to various selected targets, it is not fatal that all species are not disclosed as long as the patent provides other means of identifying which species would possess the claimed common structural characteristics or shared traits).
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
In this case the disclosure matches exactly the situation as in Enzo Biochem, as the Applicants have disclosed single species from an expansive genus. There is no indication from the disclosure that those single species are sufficient to constitute the genus and that any of the millions of possible options possess antibacterial activity and would bind to a target. The disclosed species as possessed by Applicants would not be viewed by one of ordinary skill in the art as representative of the full genus of each of SEQ ID NOs:1-4.
Accordingly, the Examiner does not find possession of the genus or that sufficient written description is provided.
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, 8, and 11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception in the form of a naturally occurring peptide without significantly more. The claim(s) recite(s) at least SEQ ID NO: 2. A search of this indicates that the sequence is found as part of an antibacterial protein from the freshwater crayfish Pacifastacus leniusculus, in particular as part of the protein Plcrustin1 (see e.g. Jiravanichpaisal et al. Development and Comparative Immunology 31:441-455, published 2007 and GenBank ABP88042). The Jiravanichpaisal/GenBank art comprises an antibacterial peptide having the sequence of SEQ ID NO: 2 where X5 is R, X6 is V, and X7 is L:
1 MRVCVMVLAL VVVTMARSPP FRPLSCPRPK VDIPGCVNTC QAKDKPGFFY ========= = 51 CCDSKGLNAG TCPKVHLQPY ERNVLCDRTQ FNYPNHLNCK DDEDCQVFEK101 CCYLPDNHQL ICRNSEDI
The underlined (=) segments indicate alignment to SEQ ID NO: 2 as claimed. This indicates that at least SEQ ID NO: 2 encompasses naturally occurring peptides having antibacterial activity.
This judicial exception is not integrated into a practical application because there is no practical application, only a linkage to a generic technical environment.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements. Therefore, the claims are deemed to be drawn to a judicial exception and are therefore ineligible.
Claim Rejections - 35 USC § 102
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 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.
1. Claims 1, 2, 8, 54, and 55 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Houghten R and Cuervo J (US 5,912,231 A1, published 15 June 1999, hereafter referred to as ‘231).
The ‘231 patent discloses an antibacterial peptide GIKKFLKKAAKFAKA (see e.g. Example 26). This comprises SEQ ID NO: 2 where X5 is K, X6 is L, and X7 is A. This also comprises SEQ ID NO: 1, where X1 is K, X2 is F, X3 is L, and X4 is A. ’231 also discloses the antibacterial peptide GIGKFLHSAKKFGKAFVGEIANS (see e.g. Col.1 lines 34-66, Table X). This comprises SEQ ID NO: 2 where X5 is K, X6 is V, and X7 is I. These anticipate claim 1.
With respect to claim 2, these sequences also constitute where X1 or X5 is lysine.
With respect to claim 8, these sequences constitute where X3 or X6 is leucine or valine.
With respect to claim 54, ‘231 discloses pharmaceutical formulations including a carrier (see e.g. Col. 6 lines 40-54).
With respect to claim 55, ‘231 discloses a dosage of 5 µg/ml in Example 26.
GIKKFLKKAAKFAKA
2. Claims 1, 8, and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jiravanichpaisal et al. (Development and Comparative Immunology 31:441-455, published 2007).
The Jiravanichpaisal art discloses three crustin antibacterial protein homologs harvested from a crayfish hemocyte EST library (see Abstract). In particular, Plcrustin1 is disclosed having a sequence
1 MRVCVMVLAL VVVTMARSPP FRPLSCPRPK VDIPGCVNTC QAKDKPGFFY ========= = 51 CCDSKGLNAG TCPKVHLQPY ERNVLCDRTQ FNYPNHLNCK DDEDCQVFEK101 CCYLPDNHQL ICRNSEDI
The underlined (=) segments indicate alignment to SEQ ID NO: 2 as claimed, in this case comprising an antibacterial peptide where X5 is R, X6 is V, and X7 is L. This anticipates claim 1.
With respect to claim 8, X6 is valine.
With respect to claim 11, X7 is leucine.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY J MIKNIS whose telephone number is (571)272-7008. The examiner can normally be reached M-F 9-5.
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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.
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/ZACHARY J MIKNIS/Patent Examiner, Art Unit 1658