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
Application status
In response to the previous Office action, a non-Final rejection (mailed on 09/05/2025), Applicants filed a response and amendment received on 03/04/2026. Said amendment canceled claims 2-3, 6, 8, 10-13, 15-17, 19, 22-23, 25, 27-29, 31-32, 35, 37-42, 46 and 48-57, amended claims 1, 4 and 18, and added claims 61-62. Thus, Claims 1, 4-5, 7, 9, 14, 18, 20-21, 24, 26, 30, 33-34, 36, 43-45, 47 and 58-62 are at issue and present for examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/03/2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112 - MAINTAINED
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 previous rejection of Claim 18 under 35 U.S.C. 112(b), 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, is maintained.
Claim 18 recites the phrase “non-standard amino acid” which is indefinite and unclear. There is no definition of the noted phrase, and therefore, it is unclear what the metes and bounds of a “non-standard amino acid” is. In the interest of advancing prosecution, the noted phrase is interpreted as “ornithine” as disclosed in claim 20.
Applicants’ Arguments:
Applicants argue that the term "non-standard amino acid" is clear based on the as-filed application, which describes non-standard amino acids as amino acids that are modified or unusual compared to the 20 "standard" amino acids (see, e.g., paragraph [0073]). The as-filed specification also provides more than 30 examples of non-standard amino acids, including ornithine (see, e.g., paragraph [0073]). Accordingly, based on the description and examples provided in the as-filed specification, a person of ordinary skill in the art would readily understand the metes and bounds of the term "non-standard amino acid."
Examiner’s Explanation:
Applicants’ arguments have been fully considered but are not deemed persuasive for the following reasons. Contrary to Applicants’ allegation, the noted phrase is only exemplified in the specification, and as such, the phrase is not defined. In other words, it is not clear what the metes and bounds of what is included and what is excluded from the meaning of "non-standard amino acid" is.
Claim Rejections - 35 U.S.C. § 102 - WITHDRAWN
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The previous rejection of Claims 1-2, 11-12, 14, 18, 20-21, 24, 26, 30, 33-34, 36, 43-45, 47 and 58-59 under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Christensen et al. (WO2020/055812 published on 03/17/2020, see IDS) is withdrawn because Applicants have inserted the limitation of claim 3 into claim 1.
Claim Rejections - 35 U.S.C. § 103 – MAINTAINED as necessitated by Applicants’ amendment to claims
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The previous rejection of Claim 1-5, 7, 9, 11-12, 14, 18, 20-21, 24, 26, 30, 33-34, 36, 43-45, 47 and 58-60 under 35 U.S.C. 103 as being unpatentable over Christensen et al. (WO2020/055812 published on 03/17/2020, see IDS) in view of Xing et al. (Multifaceted Functions of Host Cell Caveolae/Caveolin-1 in Virus Infections, Viruses 2020, 12, 487, pages 1-24, see IDS), and Rao (WO2021/195723 with earlier filing date of 04/03/2020), is withdrawn in favor of a new rejection of record as shown below which is necessitated by Applicants’ amendment to claims.
Claim 1, 4-5, 7, 9, 14, 18, 20-21, 24, 26, 30, 33-34, 36, 43-45, 47 and 58-62 are rejected under 35 U.S.C. 103 as being unpatentable over Christensen et al. (WO2020/055812 published on 03/17/2020, see IDS) in view of Xing et al. (Multifaceted Functions of Host Cell Caveolae/Caveolin-1 in Virus Infections, Viruses 2020, 12, 487, pages 1-24, see IDS), and Rao (WO2021/195723 with earlier filing date of 04/03/2020).
The instant claims are drawn to a method of treating or preventing pathogen-induced lung injury in a subject comprising administering to the subject a therapeutically effective amount of a modified Cav-1 peptide: (i) consisting of any one of SEQ ID NOs: 4-20; or (ii) comprising any one of SEQ ID NOs: 4-20 with one or more amino acid substitutions, insertions, deletions, or modifications; wherein the pathogen-induced lung injury is caused by a coronavirus infection.
Christensen et al. specifically teach a method of treating or preventing pathogen-induced lung injury, i.e., viral infection, plastic bronchitis, chronic obstructive pulmonary disease, bronchitis, bronchiolitis, bronchiolitis obliterans, asthma, acute respiratory distress syndrome (ARDS) or inhalational smoke induced acute lung injury (ISALI) in a subject comprising administering to the subject a therapeutically effective amount of a modified Cav-1 peptide: (i) consisting of any one of SEQ ID NOs: 4-20; or (ii) comprising any one of SEQ ID NOs: 4-20 with one or more amino acid substitutions, insertions, deletions, or modifications (see para [0016], [0021], [0046], [00129]; and Table 1). It is noted by the Examiner that all of the Applicants’ SEQ ID NOs: 4-20 are 100% identical to those taught in Table 1 of Christensen et al.
Claim 14 is included in this rejection because Christensen et al. teach the modified Cav-1 peptide comprising (a) L-amino acids; (b) D-amino acids; or (c) both L- and D-amino acids (see claims 5-7).
Claims 18 and 20 are included in this rejection because Christensen et al. teach the modified Cav-1 peptide comprises at least one non-standard amino acid, ornithine (see claims 9 and 11).
Claims 21 and 24 are included in this rejection because Christensen et al. teach. the modified Cav-1 peptide comprises: (a) an N-terminal modification; (b) a C-terminal modification; or (c) an N-terminal and C-terminal modification, wherein the N-terminal modification is acylation and/or the C-terminal modification is amidation (see claims 12-16).
Claims 33 and 34 are included in this rejection because Christensen et al. teach the modified Cav-1 peptide comprises an internalization sequence, i.e. cell penetrating peptide (CPP), wherein the internalization sequence is inherently located at the N- and/or C-terminus of the peptide (see claim 24).
Claim 36 is included in this rejection because Christensen et al. teach that the modified Cav-1 peptide further comprises a cap at the N- and/or C-terminus (see para [0057]).
Claim 43 is included in this rejection because Christensen et al. teach that the modified Cav-1 peptide is administered to the lung (see claim 62).
Claims 44, 45 and 47 are included in this rejection because Christensen et al. teach that the modified Cav-1 peptide is formulated for inhalation, wherein the modified Cav-1 peptide is formulated for pressurized metered dose inhalation or nebulization using nebulizer (see claim 60).
Claim 58 included in this rejection because Christensen et al. teach that the modified Cav-1 peptide comprises a pharmaceutically acceptable carrier (see para [0013]).
Claim 59 is included in this rejection because Christensen et al. teach that the method further comprises administering to the subject a therapeutically effective amount of at least one additional therapeutic agent (see claims 63 and 64).
Claims 61-62 are included in this rejection because the pharmaceutical composition taught by Christensen et al. is subcutaneously or intravenously administered (see para [0013]).
Christensen et al. do not teach that viral infection is a coronavirus infection selected from MERS-CoV, SARS-CoV-1 or SARS-CoV-2, optionally administering at least one additional therapeutic agent is chloroquine, hydroxychloroquine, remdesivir, favipiravir, lopinavir, or ritonavir.
Xing et al. teach that Caveolae/Caveolin-1 (Cav-1) plays many different roles in virus infections, i.e., virus entry, entry of enveloped and non-enveloped human/animal viruses including HCov-229E, HCoV-OC43, CRCoV (coronavirus), and SARS-CoV (see Table 1 and its related discussion below on page 4).
Rao teach that a method of reducing or preventing entry of a coronavirus into a cell comprising exposing the cell to an antiviral agent, wherein the coronavirus is selected from the group comprising SARS-CoV, SARS-CoV-2, and MERS-CoV, wherein the antiviral agent is selected from the group comprising hydroxychloroquine, chloroquine, lopinavir, ritonavir, favipiravir, and remdesivir (see all claims, especially claims 7, 28, 44 and 52).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to practice the methods taught by Christensen et al. for coronavirus infections from SARS-CoV, SARS-CoV-2, and MERS-CoV while co-administering antiviral agent is selected from the group comprising hydroxychloroquine, chloroquine, lopinavir, ritonavir, favipiravir, and remdesivir as taught by Xing et al. and Rao. One would have been motivated to practice such methods because administration of modified Cav-1 peptides provide anti-apoptotic and anti-fibrotic effects in lung epithelial cells and fibroblasts, emphasizing the protective functions of Cav-1 against fibrosis, epithelial cell death, inflammation after lung infection has occurred (italicized for added emphasis) as taught by Christensen et al. (see Examples 2 and 3 on pages 41-42), and because co-administration with other known anti-viral drugs will ameliorate the treatment against the coronaviruses (as taught by Xing et al. and Rao). One would have had a reasonable expectation of success to practice such methods because all of the required biochemical reagents and techniques were rampantly available as evidenced by Christensen et al., Xing et al. and Rao prior to the filing of the instant application. For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
Applicants’ Arguments:
Applicants argue that a person of ordinary skill in the art would have no reason or motivation to look to Xing or Rao, which describe, for example, the use of antiviral drugs to treat coronavirus infections.
Moreover, Xing teaches that caveolin-1 facilitates entry of various coronaviruses into host cells (see, e.g., HCoV-OC43 and HCoV-229E at Table 1 of Xing). Therefore, if a person of ordinary skill in the art were to consult Xing, they would be discouraged from using a modified caveolin-1 variant because the modified caveolin-1 variant could increase viral entry and exacerbate disease. Rather, such a person would be more likely consider the use of a caveolin-1 antagonist to address complications associated with coronavirus infection, as suggested by Xing (see, e.g., Abstract of Xing).
Examiner’s Explanation:
Applicants’ arguments have been fully considered but are not deemed persuasive for the following reasons. Contrary to Applicants’ argument regarding ‘lack of motivation’ based on the narrow reading of the reference of Xing et al., teachings of Xing et al. does not teach away but expressly motivates one of skill in the art to use Cav-1 peptide for treatment of coronavirus infections because of the multifaceted functions of Cav-1 peptide in every step of the viral infection cycle, i.e., viral entry, trafficking network of viruses, expression of viral proteins, viral replication, virion release, (see Figure 2 on page 9), in addition to experimental evidence indicating that SARS-CoV prefers a clathrin-mediated endocytosis, while another shows tens of Cav-1 binding domains on SARS-CoV proteins indicating that SARS-CoV hijack Cav-1 pathways (see page 4, lines 11-20). Taken together, one of ordinary skill in the art would have been motivated to practice such methods because administration of Cav-1 peptides provide anti-apoptotic and anti-fibrotic effects in lung epithelial cells and fibroblasts, emphasizing the protective functions of Cav-1 against fibrosis, epithelial cell death, inflammation after lung infection has occurred (italicized for added emphasis) as taught by Christensen et al. (see Examples 2 and 3 on pages 41-42), and because co-administration with other known anti-viral drugs will ameliorate the treatment against the coronaviruses (as taught by Xing et al. and Rao).
If Applicants’ arguments were true that Cav-1 increased more coronaviruses to enter the cells, thereby increasing viral entry/infection, are Applicants arguing that the claimed method of treating coronavirus infection is not enabling for a person of ordinary skill in the art to practice since the modified Cav-1 peptide taught by Christensen et al. are 100% identical to Applicants’ SEQ ID NOs 4-20 (italicized for added emphasis)?
For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
Conclusion
Claims 1, 4-5, 7, 9, 14, 18, 20-21, 24, 26, 30, 33-34, 36, 43-45, 47 and 58-62 are rejected for the reasons as stated above. Applicants must respond to the objections/rejections in this Office action to be fully responsive in prosecution.
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 extension fee 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 JAE W LEE whose telephone number is (571)272-9949. The examiner can normally be reached on M-F between 9:00-6:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (571)272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAE W LEE/
Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656