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 .
Priority
This is a National Stage Entry under 35 U.S.C. 371 of International Patent Application
No. PCT/EP2021/074987, filed September 10, 2021. This application also claims priority to EP Provisional Application No. EP20195554.9, filed on September 10, 2020.
Claim Objections
Claims 51 – 53, 56, 59 – 60, 62 – 63, and 65 – 66 are objected to because of the following informalities: the claims read “a chimeric or fusion protein according to claim”. The claims should read “the chimeric or fusion protein of claim.” Appropriate correction is required.
Claim 67 objected to because of the following informalities: the claim should be amended to recite “A composition comprising: the chimeric or fusion protein of claim 50, and an adjuvant.” Appropriate correction is required.
Claims 68 – 72 are objected to because of the following informalities: the claims read “a composition according to claim”. The claims should read “the composition of claim”. Appropriate correction is required.
Claim 73 is objected to because of the following informalities: the claim recites “a chimeric or fusion protein according to claim 50”. The claim should be amended to recite “the chimeric or fusion protein of claim 50.” Appropriate correction is required.
Claims 74 and 75 are objected to because of the following informalities: the claims read “A method according to claim”. The claims should read “the method of claim.” Appropriate correction is required.
Claims 51 – 53, 56, and 63 are objected to because of the following informalities: the claims read “an amino acid sequence”. The claims should read “the amino acid sequence.” Appropriate correction is required.
Claim 65 is objected to because of the following informalities: the claims read “a sequence”. The claim should read “the amino acid sequence.” 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 51 – 53, 56, 59 – 60, 62 – 63, and 65 – 75 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.
Claim 51 references Table 3, which is presented in the instant Specification, but is not present in the instant claims. "Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993); see MPEP 2173.05(s).
Claims 56, 63, and 65 recite the broad recitation “comprises” and also recite “consists essentially of” or “consists of.” It is unclear which transitional term(s)/phrase(s) is/are actually intended to narrow the claims. For purposes of compact prosecution and applying prior art, the claims were broadly interpreted to require the transitional term “comprising.”
Claim 71 contains the trademark/trade names “ImmuFact® IMP321, ISCOMATRIX®, Montanide TM IMS 1312, Montanide TM ISA 206, Montanide TM ISA V, Montanide TM ISA-51, ONTAK®, Aquila's QS21 stimulon®, PEPTEL®, MF59®”, “Addavax TM”, “Amplivax TM”, “LipoVac TM”, and “JuvImmue TM”. Claim 72 contains the trademark/trade name “MF59®”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe adjuvants and, accordingly, the identification/description is indefinite.
Regarding claim 62, the claim language ‘preferably’ renders the limitations because it is unclear if the claims specifically require such limitation(s) or not.
Regarding claim 69, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Interpretation
Regarding claims 56, 63, and 65, the claims will be broadly interpreted to encompass the transitional term comprising.
Claim Rejections - 35 USC § 102
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.
Claim(s) 50 – 52, 56, 59 – 60, 66 – 67, and 73 – 75 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sun et al (bioRxiv, November 2020, hereinafter, “Sun”) as evidenced by Zhang (Cell, September 2020, hereinafter, “Zhang”).
In regards to claim 50, Sun discloses a recombinant Fc-fusion vaccine of RBD to induce protection against SARS-CoV-2 in non-human primate and mice (Abstract). This recombinant subunit vaccine is comprised of two receptor binding domains (RBD) of the SARS-CoV-2 spike protein fused to the Fc domain of human IgG1 (Abstract, Figure 1).
Regarding claims 51 and 52, Sun discloses that the RBD to comprise an amino acid sequence of WT SARS-CoV-2 strain (“Here three epidemic strains BJ08, BJ05 and BJ01, which shared the same RBD sequence as our RBD-Fc vaccine”), as evidenced by Zhang (Figure S1). While, Sun does not explicitly recite the sequence, Sun cites the RBD sequence used to create an mRNA vaccine targeting the RBD of SARS-CoV-2 by Zhang as a reference to the RBD used by Sun. Here Sun teaches that the RBD sequence used in the RBD-Fc vaccine has a shared sequence with three WT epidemic strains and also reference Zhang which teaches the explicit sequence of the RBD.
Regarding claims 56 and 66, the sequence used by Sun, as evidenced by Zhang, has 100% identity to SEQ ID NO:15 (reproduced below from Zhang Figure S1).
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Regarding claims 59 and 60, Sun discloses a “dimer-based RBD-Fc Vacc against SARS-CoV-2 was developed by fusing RBD (aa331-524) with human IgG1 Fc.”
Regarding claims 67 and 75, Sun disclosess administering the RBD-Fc vaccine with the adjuvant of aluminum (“In summary, our data demonstrated that RBD-Fc Vacc, with adjuvant of aluminum, induced a robust humoral immune response and protected non-human primate and hACE2 Tg mice from SARS-CoV-2 infection”)
Regarding claims 73 and 74, Sun discloses an immune response within a subject by administering the RBD-Fc vaccine (Figure 2). Following the initial RBD-Fc vaccine administration, mice were challenged with one of three epidemic strain SARS-CoV-2 viruses to test for RBD-Fc vaccine efficacy (Figure 2).
Accordingly, the claimed invention was anticipated by Sun.
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.
Claim(s) 53 and 62 – 63 are rejected under 35 U.S.C. 103 as being unpatentable over Sun as applied to claims 50 – 52, 56, 59 – 60, 66 – 67, and 73 – 75 above, and further in view of Kreyes et al (US20240376180).
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Kreyes SEQ ID 165 is Sequence1, SEQ ID NO: 28 is Sequence2)]As discussed above, claims 50 – 52, 56, 59 – 60, 66 – 67, and 73 – 75 were anticipated by Sun. The reference fails to teach the sequence of the RBD of both wild type and beta strain SARS-CoV-2, the Fc, or the fused RBD-Fc protein. However, regarding claim 53, Kreyes teaches human recombinant antibodies and antibody fragments that bind to the RBD of SARS-CoV-2 (Abstract). Sequence listed as SEQ ID 1 in Kreyes, teaches an RBD-FC amino acid sequence of that is comprised of SEQ ID NO: 15 (SEQ ID NO 1: reproduced below). Kreyes also teaches the beta strain RBD-FC amino acid sequence of that is comprised of SEQ ID NO: 28 (SEQ ID 165: reproduced below).
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KREYES SEQ ID 1 is Sequence1, SEQ ID NO: 15 is Sequence2)]
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Kreyes SEQ ID 16 is Sequence1, SEQ ID NO:18 is Sequence2)]Regarding claim 62 and 63, Kreyes also teaches the RBD fused to a Fc, where the Fc region is comprised of the heavy chain fragment (see Kreyes SEQ ID 1 and 165). Kreyes also teaches recombinant monoclonal antibodies comprised of a Fc heavy chain with a sequence comprised of SEQ ID NO: 18 (reproduced below).
Sun and Kreyes are considered to be analogous to the claim invention because they both aim to treat or lessen SARS-CoV-2 infections. Sun teaches that the use RBD-Fc, along with an adjuvant of aluminum, was commonly known at the time of the claimed invention (“our data demonstrated that RBD-Fc Vacc, with adjuvant of aluminum, induced a robust humoral immune response”). Kreyes teaches the use of antibodies targeted against the RBD and spike protein of SARS-CoV-2 (Abstract). Kreyes also teaches the sequence of wild type and beta strain RBD of SARS-CoV-2 fused to Fc as well as the sequence of Fc used by the instant application (see sequence reproduced above).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to utilize the art-recognized sequences of WT and beta strain RBD and Fc, as taught by Kreyes, in the RBD-Fc fusion vaccine, as taught by Sun, because doing so would advantageously allow one to target and treat infections caused by bought wild type and beta strains of SARS-CoV-2. One of ordinary skill in the art would have had a reasonable expectation of success in producing RBD-Fc with the exact sequences taught by Kreyes given that the sequence and RBD-Fc vaccination is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim(s) 65 is rejected under 35 U.S.C. 103 as being unpatentable over Sun as applied to claims 50 – 52, 56, 59 – 60, 66 – 67, and 73 – 75 above, and further in view of Kreyes and Chen et al (Adv Drug Deliv Rev, 2013, hereinafter, “Chen”).
As discussed above, claims 50 – 52, 56, 59 – 60, 66 – 67, and 73 – 75 were anticipated by Sun. The reference fails to teach a linker between the RBD and Fc components of the RBD-Fc fusion protein.
Regarding claim 65, SEQ ID NO: 22 corresponds to the beta strain SARS-CoV-2 RBD of SEQ ID 28, a linker, and the Fc of SEQ ID NO:18. As discussed above, Kreyes teaches both of these components but does not teach the exact combination in one protein.
However, Chen teaches that linkers improve biological activity of fusion proteins and that IgG1 fusion proteins that use linkers achieve enhanced therapeutic effects (Abstract, Introduction ¶1).
Sun, Kreyes, and Chen are considered to be analogous to the claim invention because they both aim to treat or lessen infections. Sun teaches that the use RBD-Fc, along with an adjuvant of aluminum, was commonly known at the time of the claimed invention (“our data demonstrated that RBD-Fc Vacc, with adjuvant of aluminum, induced a robust humoral immune response”). Kreyes teaches the use of fusion protein antibodies comprised of a RBD portion and an Fc portion targeted against the RBD and spike protein of SARS-CoV-2 (Abstract). Chen teaches the improvement of fusion protein efficacy with the inclusion of a linker sequence (Abstract).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to utilize the art-recognized to use a linker sequence, as taught by Chen, between the RBD portion and Fc portion in the RBD-Fc fusion vaccine, as taught by Sun, because doing so would advantageously allow one to have a flexible fusion protein that is not limited by steric hinderance. One of ordinary skill in the art would have had a reasonable expectation of success in producing RBD-Fc with a linker sequence in between the RBD and Fc given that the use of linker sequences in fusion proteins is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim(s) 68 and 69 are rejected under 35 U.S.C. 103 as being unpatentable over Sun as applied to claims 50 – 52, 56, 59 – 60, 66 – 67, and 73 – 75 above, and further in view of Sekiya et al (Biomaterials, 2017, hereinafter, “Sekiya”).
As discussed above, claims 50 – 52, 56, 59 – 60, 66 – 67, and 73 – 75 were anticipated by Sun. The references fail to teach the use of a TLR2 agonist as an adjuvant for the RBD-Fc vaccine.
However, Sekiya teaches the mechanisms behind PEGylated R4Pam2Cys, an agonist for TLR2, during vaccination and that R4Pam2Cys is used as an adjuvant in vaccines (Abstract).
Sun and Sekiya are considered to be analogous to the claim invention because they both aim to treat or lessen infections. Sun teaches that the use RBD-Fc, along with an adjuvant of aluminum, was commonly known at the time of the claimed invention (“our data demonstrated that RBD-Fc Vacc, with adjuvant of aluminum, induced a robust humoral immune response”). Sekiya teaches R4Pam2Cys are commonly used adjuvants in vaccines (Abstract).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to utilize the art-recognized adjuvant taught by Sekiya in the RBD-Fc vaccine taught by Sun because doing so would increase the therapeutic effects of the RBD-Fc vaccine as has been shown with other vaccines. One of ordinary skill in the art would have had a reasonable expectation of success in increasing the vaccines efficacy given that R4Pam2Cys as an adjuvant is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim(s) 70 is rejected under 35 U.S.C. 103 as being unpatentable over Sun as applied to claims 50 – 52, 56, 59 – 60, 66 – 67, and 73 – 75 above, and further in view of Roßmann et al (Universitats Bibliothek Mainz, December 10, 2020, hereinafter, “Roßmann”).
As discussed above, claims 50 – 52, 56, 59 – 60, 66 – 67, and 73 – 75 were anticipated by Sun. The references fail to teach the use of a TLR2 agonist as an adjuvant for the RBD-Fc vaccine.
However, Roßmann teaches adjuvants that are optimal in vaccines against newly emerging viruses such as SARS-CoV-2 (Abstract). Roßmann goes on to teach the biological role PAM3CSK4 plays as adjuvant in vaccines (Abstract).
Sun and Roßmann are considered to be analogous to the claim invention because they both aim to treat or lessen infections. Sun teaches that the use RBD-Fc, along with an adjuvant of aluminum, was commonly known at the time of the claimed invention (“our data demonstrated that RBD-Fc Vacc, with adjuvant of aluminum, induced a robust humoral immune response”). Roßmann teaches that PAM3CSK4 are commonly used adjuvants in vaccines (Abstract).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to utilize the art-recognized adjuvant taught by Roßmann in the RBD-Fc vaccine taught by Sun because doing so would increase the therapeutic effects of the RBD-Fc vaccine as has been shown with other vaccine. One of ordinary skill in the art would have had a reasonable expectation of success in increasing the vaccines efficacy given that PAM3CSK4 as an adjuvant is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim(s) 71 and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Sun as applied to claims 50 – 52, 56, 59 – 60, 66 – 67, and 73 – 75 above, and further in view of Liu et al (Vaccine, September 2020, hereinafter, “Liu”).
As discussed above, claims 50 – 52, 56, 59 – 60, 66 – 67, and 73 – 75 were anticipated by Sun. The references fail to teach the use of MF59™ as an adjuvant for the RBD-Fc vaccine.
However, Liu teaches a chimeric protein that is comprised of the RBD of SARS-CoV-2 linked to an Fc region of an antibody. Liu uses this RBD-Fc in combination with the adjuvant MF59™ (Introduction, ¶4).
Sun and Liu are considered to be analogous to the claim invention because they both aim to treat or lessen SARS-CoV-2 infections using RBD-Fc. Sun teaches that the use RBD-Fc, along with an adjuvant of aluminum, was commonly known at the time of the claimed invention (“our data demonstrated that RBD-Fc Vacc, with adjuvant of aluminum, induced a robust humoral immune response”). Liu teaches that MF59TM is a commonly used adjuvant with the RBD-Fc vaccines (¶4).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to utilize the art-recognized adjuvant taught by Liu in the RBD-Fc vaccine taught by Sun because doing so would increase the therapeutic effects of the RBD-Fc vaccine as has been shown with other vaccines. One of ordinary skill in the art would have had a reasonable expectation of success in increasing the vaccines efficacy given that MF59TM as an adjuvant is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Conclusion
NO CLAIMS ARE ALLOWED
Prior art not discussed in this office action but relevant to the subject matter:
Schulze et al (Vaccine, 2008)
Ren et al (Vaccine, July 2020)
Liu, Z et al (signal transduction and targeted therapy, November 2020)
Proud et al (eBioMedicine, December 3, 2020)
Caproni et al (J Immunology, 2012)
Lan et al (Mol Pharma, 2012)
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Danyal H Alam whose telephone number is (571)272-1102. The examiner can normally be reached M - F 9am - 5pm.
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/DANYAL HASSAN ALAM/ Examiner, Art Unit 1672
/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672