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
Acknowledgement is hereby made of receipt and entry of the communication filed on Mar. 26, 2026. Claims 1-30 are pending. Claims 1-2, 5, 8-11 and 13-14 are currently examined. Claims 3-4, 6-7, 12, 15 and 16-30 are withdrawn.
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-15), in the reply filed on Mar. 26, 2026, is acknowledged.
For species election requirement, applicant made election with traverse. The applicant elected claim 5 from claims 3-7, elected claim 11 between claims 11-12 and elected claim 13 between claims 13 and claim 15.
Applicant argues that it should be no undue burden on the Examiner to consider all claims in the single application, and a search directed to one Group would likely yield results applicable to other groups. Also, Applicant argues that a species on the grounds that a search of all the alleged species could be made by the Examiner without an undue burden, and that the results of any such search would likely bear on all of the alleged species.
Applicant’s argument is not persuasive.
Although related, the inventive groups and species vary substantially that the searches are not coextensive and each distinct Group or species requires its own search and considerations of other patentability issues as the art relating to one Group would not provide the structural elements required for the other Group or other species. Thus, the search would be an undue burden on the Patent and Trademark Office resources due to the complex nature of the search in terms of computer time needed to perform the search and the subsequent analysis of the search results by the examiner.
For the reasons above, the Restriction is deemed to be proper, and is made FINAL. Accordingly, claims 16-30 are withdrawn as being drawn to a nonelected Group. Claims 3-4, 6-7, 12 and 15 are withdrawn as be directed to a nonelected species.
Claim Objection
The claim 2 is objected to because of the following informalities:
The claim 2 recites “The method of claim 1, which further comprises one or more antibodies that bind to a SARS-CoV-2 spike protein or SARS-CoV-1 spike protein”, where a word “administering” should be added after the “comprises”.
Appropriate correction is required.
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 1-2, 5, 8-11 and 13-14 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.
The base claim 1 recites a term “anti-fibrin/ anti-fibrinogen antibodies”, where the “slash (/)” renders the claims indefinite. It is not clear if it represents “and” or “or” or “and/or”. There are no metes and bounds of the claims.
Claims 11 recites a phrase “…bind to at least one epitope with peptide sequence SEQ ID NO:2…”, where the “with peptide sequence “renders the claim indefinite. It is unclear if it means “consist of” or ‘comprise”.
For purposes of compact prosecution and applying prior art, claim 11 was interpreted herein to encompass the epitopes consisting of the claimed peptide sequences.
Claim 14 recites the phrase “the SARS-CoV-2 is non-infectious SARS-CoV-2 or non-infectious SARS-CoV-1” that renders the claim indefinites. It is unclear how SARS-COV-2 is non-infectious SARS-CoV-2 or non-infectious SARS-CoV-1.
Also, it is not clear what the “non-infectious SARS-CoV-2 or non-infectious SARS-CoV-1” means. The instant specification does not disclose what the “non-infectious SARS-CoV-2 or non-infectious SARS-CoV-1” is. In addition, claim 14 is dependent on claim 1, however, the base claim 1 claims that the subject is infected with SARS-COV-2 or SARS-COV-1 that means the SARS-COV-2 and SARS-COV-1 is infectious.
Accordingly, one of ordinary skill in the art will not know the metes and bounds of the claim.
For purposes of compact prosecution and applying prior art, claim 14 was interpreted herein to encompass any types of non-infectious SARS-CoV-2 or non-infectious SARS-CoV-1 such as VLP particles.
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 (e), 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 8 and 11 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. Claims 8 and 11 are lack of additional steps and directed to an inherent feature of claim 1. Thus, they do not further limit the base claim 1
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.
Claim Rejections - 35 USC § 103
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.
Claims 1, 5, 8-11 and 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Akassoglou et al. (US 2012/0183560 A1, published on Jul. 19, 2012, hereinafter “Akassoglou”) in view of Bouck et al. (Arterioscler Thromb Vasc Biol. 2021 Jan;41(1):401-414, Epub 2020 Nov 16), and Hanaoka et al. (bioRxiv preprint doi: https://doi.org/10.1101/2020.09.06.284596; this version posted September 8, 2020).
The base claim 1 is directed to a method comprising administering a composition comprising anti-fibrin/ anti-fibrinogen antibodies to a subject infected with SARS-CoV-2 or SARS-CoV-1.
Akassoglou teaches an isolated antibody that binds a fibrin or fibrinogen yC domain. In various aspects, the antibody inhibits microglial adhesion to the fibrin or fibrinogen yC domain, inhibits Mac-1 binding to the fibrin or fibrinogen yC domain, and/or suppresses clinical symptoms of Experimental Autoimmune Encephalomyelitis (EAE). Various methods of using the antibodies, pharmaceutical compositions, kits, vectors, cells comprising the vectors, and antibody generating methods are provided.an invention (Abstract), and the method comprising administering the antibody to a subject (See claim 18, page 22), where the subject includes human and veterinary subjects ([0060]). Akassoglou also discloses that their invention provides monoclonal antibodies that inhibit fibrinogen-Mac-1 binding (See [0061]) that have the ability to inhibit inflammatory demyelination in vitro and in vivo and reduce the pro- inflammatory effects of fibrinogen in the brain and elsewhere in a subject while at the same time retaining the beneficial effects of fibrinogen in blood clotting, unlike compounds that affect blood clotting (See [0062]).
However, Akassoglou does not teaches that the subject infected with SARS-CoV-2 or SARS-CoV-1.
Bouck describes that COVID-19 is associated with different abnormalities in plasma procoagulant and fibrinolytic activity and teaches that patients with COVID-19 have enhanced plasma fibrin formation potential (See page 6, paragraph 3). Bouck also teaches that elevated fibrinogen may drive fibrin deposition in both COVID-19. Elevated fibrinogen is associated with increased risk of thrombosis, as well as inflammatory disease (See page 9, paragraph 3).
Hanaoka teaches a novel and potent thrombolytic fusion protein consisting of anti-insoluble fibrin antibody and mutated urokinase and discloses that hypercoagulation occurs not only in cardiovascular diseases, but also in cancer and severe infectious diseases such as influenza and coronavirus infection, worsening their pathologies. In patients with such severe conditions, administration of thrombolytic agents should be carried out with caution, and safer forms of administration are desirable (See Abstract and introduction). Hanaoka teaches they successfully constructed a fusion protein of mutated UK and anti-IF (insoluble fibrin) mAb, AMU1114, and confirmed that it retained the activity of UK. When UK and AMU1114 were administered to mice, the reduction in plasminogen was more strongly suppressed by AMU1114 than by UK, indicating that AMU1114 is safer than UK. Also, AMU1114 had a greater thrombolytic effect than tPA, as reflected by the larger number of individuals with reopened blood vessels. (See page 19, paragraph 1). Here these descriptions indicate that the virus such as coronavirus can cause blood hypercoagulation and the anti-fibrin antibody can be used to administer into the animal for a greater thrombolytic effect than tPA. Hanaoka also discloses that AMU1114 recognizes only IF, the mAb can be delivered to IF exclusively at lesion sites in vivo without being neutralized by precursors or degradation products in blood, AMU1114 acts selectively on IF in lesions, and the fusion protein can function for a sufficiently long time in the lesion (See page 20, paragraph 1).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce the teachings of Bouck and Hanaoka into Akassoglou’s study to arrive at an invention as claimed. One of skill in the art would have been motivated to do so because Akassoglou teaches that a therapeutically effective amount of anti-fibrin/ anti-fibrinogen antibodies to the amount needed to achieve a therapeutic objective can be a binding interaction between the antibody and its target antigen that, by interfering with the functioning of the target. Bouck teaches that subjects with SARS-CoV2 have enhanced fibrin and fibrinogen levels and Hanaoka teaches that an anti-fibrin antibody AMU1114 can be injected into a PIT mice model to provide a greater thrombolytic effect and the virus such as a coronavirus can induce the hypercoagulation. There would be a reasonable expectation of success to develop such a method comprising administering anti-fibrin/ anti-fibrinogen antibodies to a subject as claimed.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claim 5, Akassoglou teaches that monoclonal antibodies of the invention have the ability to inhibit phagocytosis in vitro and in vivo, block cytokine release and macrophage activation in vitro and in vivo, microglia activation in vitro and in vivo and inflammatory demyelination in vitro and in vivo (See [0062]) and reduce the pro-inflammatory effecting of fibrinogen in the brain and elsewhere in a subject (See bridge pages 7 and 8).
Regarding claim 8, Akassoglou teaches that all five antibodies (1A5, 1D6 and 1E3 4E11 and 5B8) are found to specifically bind increasing concentrations of full length fibrinogen. From these five antibodies three were chosen (1E3, 4El 1 and 5B8), having greater than 50% inhibition of Mac-1 binding to the fibrin or fibrinogen yC domain when measured by shift in absorbance) for isolation and large-scale purification. It is contemplated that antibodies of the invention can inhibition of Mac-1 binding to the fibrin at greater than 50%, 60% or 70% (See [0144]; Fig. 2), where the mouse IgG control is used.
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Regarding claim 9, Akassoglou teaches that the present invention provides an isolated antibody that binds a fibrin or fibrinogen yC domain. In various aspects, the antibody inhibits microglial adhesion to the fibrin or fibrinogen yC domain, inhibits Mac-1 binding to the fibrin or fibrinogen yC domain (See Abstract).
Regarding claim 10, Akassoglou teaches that the antibody of claim 1, wherein the antibody is a human monoclonal antibody (See claim 6, page 21).
Regarding claim 11, Akassoglou teaches a peptide sequences corresponding to the exact amino acids on the γ chain of fibrinogen that have been shown to be critical for the interaction of fibrinogen with Mac-1 were synthesized (Peptide #1: CGWTVLQKRIDGSL (SEQ ID NO: 17) and Peptide #2: CKKTTMKIIPFNRLTIG (SEQ ID NO:18)), where the SEQ ID NO: 18 is identical to SEQ ID NO: 2.
Regarding claim 13, Akassoglou in view of Bouck make obvious the method of claim 1, but do not teach wherein the composition is administered at a time while SARS-CoV-2 viral replication is occurring in the subject. However, Akassoglou teaches the monoclonal antibodies of the present invention reduce the pro-inflammatory effects of fibrinogen (See [0062]). Bouck teaches that subjects with SARS-Cov2 have enhanced fibrin and fibrinogen levels (Abstract). Therefore, it would have been obvious to one of ordinary skill in the art, to have used the teachings of Akassoglou and Bouck and optimized the method to use the anti-fibrin/ anti-fibrinogen antibodies in subjects with SARS-CoV2, at a time while SARS-CoV-2 viral replication is occurring in the subject, to achieve a desired treatment efficiency using routine experimentation.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Akassoglou et al. in view of Bouck et al. and Hanaoka et al. as applied to claims 1, 5, 8-11 and 13-14 above and further in view of Zhang et al. (J Hematol Oncol. 2020 Sep 4;13(1):120).
Claim 2 requires the method further comprises one or more antibodies that bind to a SARS-CoV-2 spike protein or SARS-CoV-1 spike protein.
Akassoglou, Bouck, and Hanaoka teach a method comprising administering a composition comprising anti-fibrin/ anti-fibrinogen antibodies to a subject infected with SARS-CoV-2 or SARS-CoV-1. However, it is silent on the antibodies that bind to a SARS-CoV-2 spike protein or SARS-CoV-1 spike protein.
Zhang teaches that SARS-Cov2 spike protein can enhance thrombus formation and anti-spike antibody can inhibit SARS-Cov2 spike protein induced platelet activation (See Abstract), and discloses SARS-COV-2 Spike protein activates platelets and thereby enhances thrombus formation in vivo (See page 10, right column, paragraph 3). Zhang also teaches that SARS-CoV-2 directly induces the release of coagulation factors, inflammatory cytokines, and the formation of leukocyte-platelet aggregates and the Recombinant human ACE-2 protein and an anti-Spike monoclonal antibody suppress SARS-CoV-2-induced platelet activation (See page 12).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce the teachings of Zhang into Akassoglou, Bouck, and Hanaoka’s study to arrive at an invention as claimed. One of skill in the art would have been motivated to do so because Zheng teaches that anti-Spike monoclonal antibody suppress SARS-CoV-2-induced platelet activation and thrombus formation. There would be a reasonable expectation of success to develop a method comprising antibodies that bind to a SARS-CoV-2 spike protein or SARS-CoV-1 spike protein.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Akassoglou et al. in view of Bouck et al. and Hanaoka et al. as applied to claims 1, 5, 8-11 and 13-14 above and further in view of Xu et al. (Front Bioeng Biotechnol. 2020 Sep 09; 8:1026).
Claim 14 requires the SARS-CoV-2 is non-infectious SARS-CoV-2 or non-infectious SARS-CoV-1.
Akassoglou, Bouck, and Hanaoka teach a method comprising administering a composition comprising anti-fibrin/ anti-fibrinogen antibodies to a subject infected with SARS-CoV-2 or SARS-CoV-1. However, it is silent on the SARS-CoV-2 is non-infectious SARS-CoV-2 or non-infectious SARS-CoV-1.
Xu teaches that virus-like particle (VLP) is a self-assembled nanostructure incorporating key viral structural proteins. VLP resembles molecular and morphological features of authentic viruses but is non-infectious and non-replicating due to lack of genetic materials. Successful applications of VLP have been shown in vaccinological and virological research. As an accessibly safe and relevant substitute of naturally pathogenic viruses, the construction of SARS-CoV-2 VLPs is much in demand in the ongoing fight against 2019 Coronavirus disease (COVID-19) pandemics. Their data demonstrate that SARS-CoV-2 VLPs possess molecular and morphological properties of native virion particles, which endow such VLPs with a promising vaccine candidate and a powerful tool for the research of SARS-CoV-2 (See Abstract).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce the study of Xu into the teachings of Akassoglou, Bouck and Hanaoka to arrive at an invention as claimed. One of skill in the art would have been motivated to do so because VLP-based SARS-COV-2 expressing the spike protein and it is non-infectious. There would be a reasonable expectation of success to develop a method wherein the SARS-CoV-2 is non-infectious SARS-CoV-2 or non-infectious SARS-CoV-1.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUIXUE WANG whose telephone number is (571)272-7960. The examiner can normally be reached Monday-Friday 8:00 am to 4:30 pm, EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas J. Visone can be reached on (571) 270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RUIXUE WANG/Examiner, Art Unit 1672
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