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
Response to Election/Restriction filed on November 17, 2025 is acknowledged. Claims 1-25 are pending in the instant application.
Election/Restrictions
Applicant elected without traverse SEQ ID NO:4 (referred to as 122023-A) in the reply filed November 17, 2025. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP 818.03(a)).
The restriction is deemed proper and is made FINAL in this office action.
Claims 1-25 are examined on the merits of this office action.
Specification Objection
The specification is objected to for the following reasons: Table 1 discloses SEQ ID Nos:3-7. In SEQ ID Nos:6-7, the amino acid at position 17 (Z) is defined as D or Q. However, in the sequence listing, position 17 is identified both as Glx and Z (see sequences listing for both SEQ ID Nos:6-7). In the art, Glx means Gln and Glu, not Asp and Gln. Thus, there is some confusion with regards to what amino acids are encompassed at position 17. Applicant should correct the sequence listing and specification if applicable.
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 1-25 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that 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, 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 applicant was in possession of the claimed genus.
Scope of the claims
Claims 1, 9 (a method of using the peptide of claim 1), and 18 (a second method) recite an antiviral peptide comprising an amino acid sequence that is at least 80% identical to SEQ ID NO:4, and further requiring at least one mutation relative to SEQ ID NO:3. However, the second limitation is redundant as a peptide having at least 80% sequence identity has to have more than one amino acid mutation relative to SEQ ID NO:3 and thus does not add any further limitation. Nevertheless, the language encompasses a broad and open genus of ACE2 derived peptides containing undefined numbers, type and positions of amino acids substitutions, deletions or insertions provided the numerical sequence identity and mutation conditions are met. SEQ ID NO:4 is a 23mer peptide and thus, at least 80% sequence identity allows for up to 4 amino acids to differ. The possibilities are vast given the number of different amino acids and different combinations with up to five amino acids.
Therefore, to meet the written description requirement of 35 U.S.C. § 112, first paragraph, the specification must disclose a representative number of species that meet both the structural and functional limitations of the genus or the specification and/or the prior art must identify the structural elements that correlate to the claimed function in a manner that demonstrates to one of ordinary skill in the art that Applicant was in possession of the claimed genus at the time the application was filed.
The claim does not identify which residues may vary, which are essential, or how many substitutions are permitted while retaining the antiviral activity.
Actual Reduction to Practice
MPEP § 2163 states that 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. 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.
The specification demonstrates antiviral activity for only the peptide corresponding to SEQ ID NO:4 (referred to as 122023-A), which showed inhibitory activity in neutralization assays and live SARS-Cov-2 infection assays (see Figure 5). No antiviral data is provided for SEQ ID Nos:5-7 or for any peptide falling near the lower end of the claimed 80% identity threshold. SEQ ID Nos:5-7 are peptides have 90% or greater sequence identity to SEQ ID NO:4. Accordingly, the disclosure evidences possession of only one operative species, not the breadth of the claimed genus.
Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic
MPEP § 2163 states that 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, 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 thereof.
Table 1 provides four computationally designed variants of the ACE2-derived sequence. However, the application does not establish that these sequences are representative of the entire claimed genus. For example, the residue at position 17 in SEQ ID Nos:6-7 in inconsistently described defined in the claims as Z=Asp or Gln, while the sequence listing and text define the residue as Glx (Glu or Gln). This inconsistency prevents SEQ ID NO:6-7 from serving as reliably supported species and further demonstrates that the full scope of residue variability is not clearly possessed at the time of filing.
Physical/Chemical Properties
While modeling and energetic mapping figures (Figures 1-3) illustrate theoretical effects of substitutions on charge interactions, helicity or residue spacing, the specification dos not identify which positions are essential, which variations are tolerated, or how many substitutions can be introduced while retaining folding, solubility or anti-viral activity. Without such disclosure, the physical boundaries of the claimed genus remain undefined.
Functional characteristics when coupled with a known or disclosed correlation between function and structure:
Although Figures 4-5 demonstrate antiviral activity of SEQ ID NO:4, the application does not identify a predictive structure/function role, conserved motif, or residue constraint explaining why SEQ ID NO:4 functions or which of its residues are required for antiviral activity. Thus, computational modeling alone does demonstrate that the broad range of variants encompassed by the claim retain the anti-viral function.
Method of Making
General peptide synthesis methodology is described, but routine synthesis capability does not satisfy written description where the claim encompasses an unpredictable and structurally broad genus without guidance for selecting functional variants.
Conclusion
Because the disclosure supports only a single experimentally validated antiviral peptide and provides limited computationally suggested variants without demonstrating that such variants retain antiviral activity, and due to internal inconsistency in residue definition in SEQ ID Nos:6-7, the application fails to show possession of the full claim scope.
Claims 9-25 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/inhibiting SARS-COV-2 with SEQ ID NO:4, does not reasonably provide enablement for treating any coronavirus. 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
Claim 9 is directed to a method of treating a coronavirus infection in a subject, comprising administering a therapeutically effective amount of the antiviral peptide of claim 1. Claim 18 claims a method of inhibiting coronavirus particle attachment to cells, comprising contacting the coronavirus particles with an effective amount of the antiviral peptide of claim 1. The scope of the claims include treatment of any coronavirus, including but not limited to SARS-CoV-2, SARS-CoV-1, MERS-CoV, endemic human coronaviruses (229E, NL63, OC43, HKU1 and potentially futures unidentified variants or strains. Different coronaviruses have different primary receptor interaction and relevance (for example SARS-CoV-2/1 and NL63 use ACE2 whereas MERS-CoV uses DPP4 and OC43/HKU1 use sialic acid binding.
The claim therefore encompasses broad biological diversity, including viruses with distinct receptor binding interfaces, host tropism, spike protein architecture and ACE2 affinity.
Treating viral infections is considered highly unpredictable biological filed, particularly where therapeutic effects depends on protein interaction disruption, viral entry, spike receptor usage and binding affinity. Even minor amino acid changes in coronavirus spike proteins can significantly alter host receptor interaction.
The State of the Prior Art
The field recognizes that ACE2-binding inhibitor peptides are virus specific and do not universally inhibit coronaviruses, particularly those that do not rely on ACE2 for entry. The application provides no evidence that those skill in the art would reasonably expect ACE2-derived peptides to possess broad pan-coronavirus therapeutic utility. In general, coronaviruses are diverse, have varying mechanisms of pathogenesis and modes of treatment (see Liu et al.). To date, there is not one treatment for any coronavirus. For example, Liu et al. teaches that “Different host selectivity and tissue toxicity of coronaviruses may depend on differences in spike (S) protein. The spike (S) protein of coronavirus is a type I membrane glycoprotein with multiple functional domains. It binds to the specific cell receptor through its S1 subunit and then mediates the fusion of the virus and the cell membrane through its S2 subunit [2]. SARS-CoV and SARS-CoV-2 enter the target cell through the ACE2 receptor and initiates S protein infection based on the host cell protease TMPRSS2 [31–34]. Compared to SARS-CoV, the RBD of SARS-CoV-2 binds to angiotensin converting enzyme II (ACE2) more closely and RBD residue changes make binding between the virus and receptor more stable [32]. A ten-year structure study based on SARS-CoV shows that the efficiency of SARS-CoV-2 using human ACE2 may be lower than human SARS-CoV (2002) but higher than human SARS-CoV (2003), indicating that COVID-19 has acquired some transmission power between individuals”. Liu further teaches “The MERS-CoV receptor is an exopeptidase dipeptidyl peptidase-IV (DPP IV; also known as CD26), which is a multifunctional type II transmembrane glycoprotein”. Liu teaches “The cellular susceptibility of the three coronaviruses differs. In 9 different cell tests, SARS-CoV-2 and SARS-CoV showed similar tissue tendency and replicated stably in the lung cells, intestinal cells, hepatocytes and kidney cells. The replication ability of SARS-CoV-2 in the lung and intestine was opposite to what was observed for SARS-CoV. Moreover, SARS-CoV-2 had the ability to replicate in neuronal cells. In a sensitivity study including 28 cell lines, MERS had the ability to effectively replicate in 17 cell types. In addition to respiratory tract infection, the viral load of MERS in the kidney, intestine, hepatocytes, tissue cells, neurons, monocytes and T lymphocytes increased significantly, showing a greater tissue tendency than SARS” (see Etiology section 3). Thus, clearly there are key differences the etiology and mechanisms of pathogenesis across different coronaviruses.
The Predictability or Unpredictability of the Art/ The Relative Skill of Those in the Art
Given the demonstrated variability among coronavirus receptor interactions and lack of proven mechanistic relationship that generalizes beyond SARS-CoV-2, the filed is considered highly unpredictable.
Amount of Guidance/ The Presence or Absence of Working Examples
The specification does not provide guidance concerning whether peptide activity depends on spike-ACE2 interaction, how peptide activity is predicted across coronavirus families, how to modify peptides to target non ACE2 coronaviruses. There is no screening workflow, predictive structural criteria, or viral applicability boundaries are disclosed
Other than SARS-CoV2 inhibition by SEQ ID NO:4, there are now working examples demonstrating antiviral function for additional peptide sequences claimed under the gens, additional viral targets within the coronavirus family or treatment in vivo or pharmacological effect in a subject with any coronavirus.
The Quantity of Experimentation Necessary
Given the breadth of the claim language and the lack of supporting data across the full scope, the amount of experimentation required to determine which peptides within the claimed identity (≥80% to SEQ ID NO:4) and mutation framework retain antiviral activity against each coronavirus species would be substantial.
In view of the above Wands factors, including the breadth of the claims, the limited working examples, the lack of guidance or predictive structure-function relationship, the high unpredictability of antiviral peptide design, and the substantial experimentation required to determine which peptides exhibit antiviral activity across the claimed coronavirus genus (any coronavirus), the disclosure does not enable a person of ordinary skill in the art to practice the full scope of the claimed invention without undue experimentation. Therefore, the method of treatment claims do not meet the enablement requirement of 35 U.S.C. §112(a).
Claim Rejections - 35 USC § 112
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 2-3, 11-12, 20-21 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 2, 11 and 20 all claim peptide sequences comprising SEQ ID Nos: 6-7, wherein the amino acid at position 17 is defined as “Z”, further defined as D or Q. However, in the sequence listing and in Table 1of the specification, position 17 for SEQ ID Nos:6-7 is alternatively identified as Glx and Z. As used in the art, Glx refers to Glu or Gln, whereas the symbol Z as defined in the specification refers to Asp or Gln. Because these notations correspond to different amino acid sets, it is unclear which residues are actually encompassed at position 17 of SEQ ID Nos:6 and 7 and thus, the scope of the claimed peptides cannot be determined with reasonable certainty. Applicant should clarify the amino acid definition and ensure consistency across the claims, specification and sequence listing.
Claim 3 claims “The antiviral peptide of claim 1, wherein residue 20 is tyrosine” but claim 1 doesn’t establish which sequence or number scheme is being referenced. Claim 1 recites an antiviral peptide defined by a percentage identity to SEQ ID NO:4 and by mutation relative to SEQ IDNO:3, but does not define or identify a specific residue numbering framework for the antiviral peptide. Accordingly, it is unclear whether “position 20” refers to SEQ ID NO:3, SEQ ID NO:4 or the final peptide resulting from the sequence identity and mutation requirements. The claim fails to provide clear antecedent basis (see MPEP 217.03 (e)).
Claim 12 claims “The method of claim 9 (which is dependent on claim 1), wherein residue 20 is tyrosine” but claim 1 doesn’t establish which sequence or number scheme is being referenced. Claim 1 recites an antiviral peptide defined by a percentage identity to SEQ ID NO:4 and by mutation relative to SEQ IDNO:3, but does not define or identify a specific residue numbering framework for the antiviral peptide. Accordingly, it is unclear whether “position 20” refers to SEQ ID NO:3, SEQ ID NO:4 or the final peptide resulting from the sequence identity and mutation requirements. The claim fails to provide clear antecedent basis (see MPEP 217.03 (e)).
Claim 21 claims “The method of claim 18 (which is dependent on claim 1), wherein residue 20 is tyrosine” but claim 1 doesn’t establish which sequence or number scheme is being referenced. Claim 1 recites an antiviral peptide defined by a percentage identity to SEQ ID NO:4 and by mutation relative to SEQ IDNO:3, but does not define or identify a specific residue numbering framework for the antiviral peptide. Accordingly, it is unclear whether “position 20” refers to SEQ ID NO:3, SEQ ID NO:4 or the final peptide resulting from the sequence identity and mutation requirements. The claim fails to provide clear antecedent basis (see MPEP 217.03 (e)).
Closest prior art Made of Record
The closest prior art made of record is Farzan (WO2005032487 A1). Farzan teaches “the identification of human angiotensin -converting enzyme-2 (ACE-2) as a functional receptor for the SARS coronavirus. Transfection of cells with ACE-2 confers upon them the ability to support viral replication. In addition, assays performed using ACE-2 together with the S protein of the SARS virus or a fragment derived from the S protein can be used to identify inhibitors that block the interaction between virus and host cell” (see abstract). Farzan further teaches use of a soluble ACE-2 comprising SEQ ID NO:2 (which comprises instant SEQ ID NO:3, SEQ ID NO:2 of Farzan is the native soluble ACE2 protein) and use of soluble ACE2 to block binding of S or SI to cellular receptors. However, the instant claims are drawn to variant peptides of native ACE2 with anywhere from 8-10 mutations in the specific ACE2 fragment sequence. Neither Farzan or any other prior art teaches these modifications or variants encompassed by the instant claims.
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.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654