DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1, 4-6, 11-15, and 21-28 are pending in the application.
Applicant’s amendment to the claims, filed October 24, 2025, is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks, filed October 24, 2025 in response to the non-final rejection mailed April 24, 2025 have been fully considered.
Rejections previously applied to claim 9 are withdrawn in view of the instant amendment to cancel claim 9.
Rejections previously applied to claims 21-24 are withdrawn in view of applicant’s amendment to delete the elected species of SEQ ID NO: 1 in claim 21.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in a prior Office action.
Restriction/Election
In response to a requirement for restriction/election mailed November 9, 2022, applicant elected without traverse the invention of Group I, pending claims 1, 4-6, 11-15, and 21-28, drawn to an engineered peptide for mediated degradation of a target infectious microbe, species (A), the targeting domain comprises an sACE2-derived peptide consisting of SEQ ID NO: 1, and species (AA), the ubiquitin ligase recruiting domain is an Fc domain in the reply filed April 11, 2023 and in a telephone conversation with Paul Haun on April 20, 2023.
Claims 14, 15, and 21-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim.
Claims 1, 4-6, and 11-13 are being examined on the merits.
Claim Rejections - 35 USC § 103
Claims 1, 4-6, 11, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Mourtada et al. (WO 2019/118893 A1; cited on Form PTO-892 mailed on June 2, 2023; hereafter “Mourtada”) in view of Walensky et al. (WO 2021/216845 A1 with priority to April 2020; cited on Form PTO-892 mailed on June 2, 2023; hereafter “Walensky”) and Clift et al. (Cell 172:1692-1706, 2017, e18, 34 pages; cited on Form PTO-892 mailed on June 2, 2023; hereafter “Clift”).
Claims 1, 4-6, 11, and 12 are drawn to (in relevant part) an engineered peptide for mediated degradation of a target virus, comprising:
a fusion protein comprising a targeting domain for binding to a spike protein receptor and a ubiquitin ligase recruitment domain, wherein the targeting domain comprises the amino acid sequence of SEQ ID NO: 1, and the ubiquitin ligase recruiting domain comprises an Fc domain.
Regarding claim 1, Mourtada teaches peptide degron chimeras that act as protein degradation-inducing moieties and teaches the peptide degron chimeras include combining a peptide that binds and recruits a degrader protein with a peptide, which is incorporated for targeting a disease-related protein (p. 19, first full paragraph). Mourtada teaches the degrader protein is an E3 ubiquitin ligase (p. 27, first full paragraph). Mourtada teaches the targeted proteins can be of viral origin and are involved in or that are causative of disease and the chimeras are useful for treating diseases driven by such pathologic proteins (p. 2, first full paragraph).
Mourtada does not teach or suggest the claim 1 limitation “the targeting domain comprise the amino acid sequence of SEQ ID NO: 1.”
Walensky teaches structurally stabilized peptides that target the receptor binding domain (RBD) of the spike (S) protein of SARS-CoV-2, the peptides being useful for treating coronavirus infection (Abstract; p. 37, lines 20-28). Walensky teaches an ACE2 α1 helix sequence (SEQ ID NO: 1 of Walensky) that targets the RBD of SARS-CoV-2 (paragraph bridging pp. 38-39; Table 1). SEQ ID NO: 1 of Walensky comprises the amino acid sequence of SEQ ID NO: 1 of this application.
In view of Mourtada and Walensky, it would have been obvious to one of ordinary skill in the art before the effective filing date to use the ACE2 α1 helix sequence of Walensky as the targeting peptide of the peptide degron chimera of Mourtada. One would have been motivated and would have expected success to do so because Mourtada taught a peptide degron chimera including a peptide for targeting a viral disease-related protein and Walensky teaches a peptide that targets a viral disease-related protein.
Mourtada also does not teach or suggest the claim 1 limitation “the ubiquitin ligase recruiting domain comprises an Fc domain.”
Clift teaches that antibody-bound pathogens can be recognized by the E3 ubiquitin ligase TRIM21, which binds with high affinity to the Fc domain of antibodies (p. 1692, column 2, bottom). Clift teaches that during infection, TRIM21 recruits the ubiquitin-proteasome system to antibody-bound pathogens, leading to their destruction (p. 1692, column 2, bottom). Clift teaches a fusion protein comprising an Fc domain fused to the C-terminus of a nanobody (Figure 2(I); p. e5, top) for degradation of the protein targeted by the nanobody (paragraph bridging pp. 1692-1693; p. 1694, column 2, middle).
In view of Mourtada and Clift, it would have been obvious to one of ordinary skill in the art before the effective filing date to use the Fc domain of Clift as the peptide that binds and recruits a degrader protein in the peptide degron chimera of Mourtada. One would have been motivated and would have expected success to do so because Mourtada taught a peptide degron chimera comprising a peptide that binds and recruits an E3 ubiquitin ligase for degradation of the targeted protein, and Clift taught an Fc domain fused to a peptide targeting domain (a nanobody) to recruit an E3 ubiquitin ligase (TRIM21) for degradation of the targeted protein.
Regarding claims 4-6, the combination of Mourtada, Walensky, and Clift does not teach or suggest the S protein of SARS-CoV-2 is part of a SARS-CoV-2 viral envelope. However, given that the S protein of SARS-CoV-2 is inherently part of the viral envelope of SARS-CoV-2 and the ACE2 α1 helix sequence of Walensky targets the RBD of the S protein of SARS-CoV-2 (see Abstract and p. 37, lines 20-28 of Walensky), the ACE2 α1 helix sequence of Walensky necessarily targets the S protein of the viral envelope of SARS-CoV-2.
Regarding claim 11, Clift teaches the Fc domain is fused to the C-terminus of the nanobody (Figure 2(I); p. e5, top).
Regarding claim 12, Mourtada teaches the degrader protein that is recruited by the peptide degron chimera is an E3 ubiquitin ligase (p. 27, first full paragraph) and Clift teaches the Fc domain binds to the E3 ubiquitin ligase TRIM21 (p. 1692, column 2, bottom).
Therefore, the engineered peptide of claims 1, 4-6, 11, and 12 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Mourtada in view of Walensky and Clift as applied to claims 1, 4-6, 11, and 12 above, and further in view of GenBank Database Accession Number NP_003132 (May 2019, 3 pages; cited on Form PTO-892 mailed on June 2, 2023; hereafter “GenBank”).
The relevant teachings of Mourtada, Walensky, and Clift as applied to claims 1, 4-6, 11, and 12 are set forth above.
The combination of Mourtada, Walensky, and Clift does not teach or suggest the amino acid sequence of TRIM21 is SEQ ID NO: 4.
The reference of GenBank teaches the amino acid sequence of human TRIM21 (p. 3), which is identical to SEQ ID NO: 4 of this application.
In view of Mourtada, Walensky, Clift, and GenBank, it would have been obvious to one of ordinary skill in the art before the effective filing date for the Fc domain to recruit the human TRIM21 of GenBank. One would have been motivated and would have expected success to do so because Mourtada taught the subject to be treated is a human (p. 4, bottom), Clift teaches the TRIM21 is human TRIM21 (p. e4, bottom), and GenBank teaches the amino acid sequence of human TRIM21, which is identical to instant SEQ ID NO: 4.
Therefore, the engineered peptide of claim 13 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 1, 4-6, 11, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Mourtada in view of Chatterjee et al. (US 2022/0002700 A1 with priority to April 3, 2020; cited on Form PTO-892 mailed on June 2, 2023; hereafter “Chatterjee-2”) and Clift.
Regarding claim 1, Mourtada teaches peptide degron chimeras that act as protein degradation-inducing moieties and teaches the peptide degron chimeras include combining a peptide that binds and recruits a degrader protein with a peptide, which is incorporated for targeting a disease-related protein (p. 19, first full paragraph). Mourtada teaches the degrader protein is an E3 ubiquitin ligase (p. 27, first full paragraph). Mourtada teaches the targeted proteins can be of viral origin and are involved in or that are causative of disease and the chimeras are useful for treating diseases driven by such pathologic proteins (p. 2, first full paragraph).
Mourtada does not teach or suggest the claim 1 limitation “the targeting domain comprise the amino acid sequence of SEQ ID NO: 1.”
Chatterjee-2 teaches sACE2-derived peptide variants that bind to the SARS-CoV-associated spike (S) protein (paragraph [0002]) including sACE2 peptide variant 2 (SEQ ID NO: 2 of Chatterjee-2). SEQ ID NO: 2 of Chatterjee-2 comprises the amino acid sequence of SEQ ID NO: 1 of this application.
In view of Mourtada and Chatterjee-2, it would have been obvious to one of ordinary skill in the art before the effective filing date to use the sACE2 peptide variant 2 of Chatterjee-2 as the targeting peptide of the peptide degron chimera of Mourtada. One would have been motivated and would have expected success to do so because Mourtada taught a peptide degron chimera including a peptide for targeting a viral disease-related protein and Chatterjee-2 teaches a peptide that targets a viral disease-related protein.
Mourtada also does not teach or suggest the claim 1 limitation “the ubiquitin ligase recruiting domain comprises an Fc domain.”
Clift teaches that antibody-bound pathogens can be recognized by the E3 ubiquitin ligase TRIM21, which binds with high affinity to the Fc domain of antibodies (p. 1692, column 2, bottom). Clift teaches that during infection, TRIM21 recruits the ubiquitin-proteasome system to antibody-bound pathogens, leading to their destruction (p. 1692, column 2, bottom). Clift teaches a fusion protein comprising an Fc domain fused to the C-terminus of a nanobody (Figure 2(I); p. e5, top) for degradation of the protein targeted by the nanobody (paragraph bridging pp. 1692-1693; p. 1694, column 2, middle).
In view of Mourtada and Clift, it would have been obvious to one of ordinary skill in the art before the effective filing date to use the Fc domain of Clift as the peptide that binds and recruits a degrader protein in the peptide degron chimera of Mourtada. One would have been motivated and would have expected success to do so because Mourtada taught a peptide degron chimera comprising a peptide that binds and recruits an E3 ubiquitin ligase for degradation of the targeted protein, and Clift taught an Fc domain fused to a peptide targeting domain (a nanobody) to recruit an E3 ubiquitin ligase (TRIM21) for degradation of the targeted protein.
Regarding claims 4-6, the combination of Mourtada, Chatterjee-2, and Clift does not teach or suggest the S protein of SARS-CoV-2 is part of a SARS-CoV-2 viral envelope. However, given that the S protein of SARS-CoV-2 is inherently part of the viral envelope of SARS-CoV-2 and the sACE2 peptide variant 2 of Chatterjee-2 targets the S protein of SARS-CoV-2 A (paragraph [0002] of Chatterjee-2), the sACE2 peptide variant 2 of Chatterjee-2 necessarily targets the S protein of the viral envelope of SARS-CoV-2.
Regarding claim 11, Clift teaches the Fc domain is fused to the C-terminus of the nanobody (Figure 2(I); p. e5, top).
Regarding claim 12, Mourtada teaches the degrader protein that is recruited by the peptide degron chimera is an E3 ubiquitin ligase (p. 27, first full paragraph) and Clift teaches the Fc domain binds to the E3 ubiquitin ligase TRIM21 (p. 1692, column 2, bottom).
Therefore, the engineered peptide of claims 1, 4-6, 11, and 12 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Mourtada in view of Chatterjee-2 and Clift as applied to claims 1, 4-6, 11, and 12 above, and further in view of GenBank.
The relevant teachings of Mourtada, Chatterjee-2, and Clift as applied to claims 1, 4-6, 11, and 12 are set forth above.
The combination of Mourtada, Chatterjee-2, and Clift does not teach or suggest the amino acid sequence of TRIM21 is SEQ ID NO: 4.
The reference of GenBank teaches the amino acid sequence of human TRIM21 (p. 3), which is identical to SEQ ID NO: 4 of this application.
In view of Mourtada, Chatterjee-2, Clift, and GenBank, it would have been obvious to one of ordinary skill in the art before the effective filing date for the Fc domain to recruit the human TRIM21 of GenBank. One would have been motivated and would have expected success to do so because Mourtada taught the subject to be treated is a human (p. 4, bottom), Clift teaches the TRIM21 is human TRIM21 (p. e4, bottom), and GenBank teaches the amino acid sequence of human TRIM21, which is identical to instant SEQ ID NO: 4.
Therefore, the engineered peptide of claim 13 would have been obvious to one of ordinary skill in the art before the effective filing date.
RESPONSE TO REMARKS: Applicant argues that Mourtada teaches only “small molecule degrons” to recruit degrader proteins, while claim 1 recites “an Fc domain,” which is a glycoprotein. Applicant argues that due to the differences between “small molecule degrons” and “an Fc domain,” one of ordinary skill in the art would have had no reasonable basis to substitute the “small molecule degron” of Mourtada with an Fc domain because such substitution would be directly opposed to the benefits Mourtada attributes to the use of small molecule degrons.
Applicant’s argument is not found persuasive. Contrary to applicant’s position, Mourtada explicitly teaches the alternative of a “peptide degron moiety capable of recruiting degrader proteins that degrade bound proteins” (p. 19, first full paragraph) and in view of the combined teachings of Mourtada and Clift as described in detail above, one would have been motivated and would have expected success to use the Fc domain of Clift as the peptide that binds and recruits a degrader protein in the peptide degron chimera of Mourtada.
For these reasons, it is the examiner’s position that the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Conclusion
Status of the claims:
Claims 1, 4-6, 11-15, and 21-28 are pending.
Claims 14, 15, and 21-28 are withdrawn from consideration.
Claims 1, 4-6, and 11-13 are rejected.
No claim is in condition for allowance.
THIS ACTION IS MADE FINAL. 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 DAVID J STEADMAN whose telephone number is (571)272-0942. The examiner can normally be reached Monday to Friday, 7:30 AM to 4:00 PM.
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/David Steadman/Primary Examiner, Art Unit 1656