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 .
Drawings
The drawings are objected to because Figure 1A contains an amino acid sequence that must be referenced by a sequence identifier (SEQ ID NO).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
In lieu of filing a corrected drawing sheet, the description of Figure 1A in the specification may be amended to reference the sequence identifier.
Specification
The disclosure is objected to because it contains embedded hyperlinks and/or other forms of browser-executable code on at least pages 1-3. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Further, there are numerous instances throughout the specification of words that need spaces between them, as well as spaces after commas, etc., e.g., page 2, line 5, “vaccinesthat”. Correction is required.
Priority
This application is a 371 of PCT/CU2021/050007 filed August 5, 2021. Normally, Applicant would be entitled to the benefit of priority which would be one year prior, i.e., August 5, 2020. It is noted that the specification references information obtained on August 10, 13, 17, 2020 with regard to certain websites (see pages 1-3). Since these dates occur after the August 5, 2020, the application is not entitled to the benefit of priority to August 5, 2020.
Claims Summary
Claim 1 is directed to a vaccine composition that induces an immune response to SARS-CoV-2, comprising:
An antigen comprising a portion of the RBD of SARS-CoV-2 S protein; the antigen comprises SEQ ID NO: 1 (claim 2); SEQ ID NO: 1 is 223 amino acids in length; the RBD is in the form of a dimer (claim 3) formed through disulfide bridges between two free cysteines (C538) (claim 4);
An immunopotentiating component comprising OMVs of the N. meningitidis Group B bacteria; the OMVs have a particle size range between 150-300 nm (claim 6); and
An adjuvant, specifically aluminum hydroxide, aluminum phosphate or calcium phosphate (claim 5)
The composition comprises from 5 to 50 µg of the RBD (claim 7). The composition comprises pharmaceutically suitable excipients (claim 8). Claims 10-13 are directed to “use” claims, which do not recite any active method steps.
Claim 9 is directed to a method for obtaining the OMVs of claim 6. Since the OMVs of claim 6 are not indicated in the claim as being physically bound or connected with the antigen or adjuvant of the vaccine composition, claim 9 is essentially directed to a method for obtaining OMVs of the N. meningitidis Group B bacteria having a particle size range between 150-300 nm, apart from the other components of the vaccine composition. The specification teaches that the antigen and OMVs are blended together and adsorbed in aluminum hydroxide (see page 5, lines 29-33), however, claim 6 (and independent claim 1) do not indicate the format of the composition (e.g., the composition comprises a mixture wherein OMVs adsorbed to the adjuvant, or some way to indicate how the components of the vaccine are physically arranged relative to one another). The method comprising solubilizing the OMVs in pharmaceutical grade water by agitation, and sonicating the OMVs at a temperature between 10°C.
Claim Objections
Claim 9 is objected to because of the following informality:
Claim 9 recites “OMV’s” (possessive), which should be “OMVs” (plural).
Appropriate correction is required.
Claim Rejections - 35 USC § 101
Claims 10-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because they are directed to “use” claims that do not recite any method steps. It is suggested that the claims be rewritten as, for example, “A method of preventing infection by administering the composition of claim 1 to a subject”, or equivalent language. Please note that because the claims do not recite any method steps, they will be not evaluated under 35 U.S.C. 102 or 103.
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 4 and 10-13 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 4 references disulfide bridges between “two free cysteine (C538)”. It appears that C538 refers to a position in SEQ ID NO: 1. Suggested language is “two free cysteines at position 538, corresponding to SEQ ID NO: 1, in both monomers that form the dimer”, or equivalent language, if that is Applicant’s meaning. Further, the use of parentheses renders the claim indefinite because it is not clear whether the subject matter in the parentheses is part of the claimed invention.
Claims 10-13 are directed “use” claims that do not recite any active method steps. It is suggested that the claims be rewritten as, for example, “A method of preventing infection by administering the composition of claim 1 to a subject”, or equivalent language.
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 and 3-13 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are directed to a vaccine composition comprising a portion of the RBD of the S protein of SARS-CoV-2. Thus the claims encompass a large genus of portions of the RBD, which are not limited to any particular sequence, and only defined by function (vaccine).
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
In this case, the structure provided is one species of “a portion”. That one portion of RBD provided is SEQ ID NO: 1, residues 319-541 of the RBD (see specification, page 4, lines 1-2 and 23-24, page 5, lines 8-9, Figure 1, etc.). The function provided is that the antigen, in combination with the OMVs and adjuvant is a vaccine, thus it is capable of inducing an immune response that will protect from disease upon subsequent challenge with SARS-CoV-2. Aside from the one structure, residues 319-541, no other portions of the RBD have been provided that have the required function. There is no nexus between “portions” and the required vaccine capability. The one species is not representative of the genus encompassed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
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 9 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Olivieri et al (WO 2005/004908 A1, “Olivieri”), evidenced by Roier et al. (Nat Commun 2016, 7, 10515, 13 pages, “Roier”). Claim 9 and its interpretation is outlined above in the section “Claims Summary”.
Olivieri discloses the production of OMVs from N. meningitidis (see abstract). In Example 3, OMVs are suspended in a 3% sucrose solution using agitation (solubilizing), followed by sonication at <20°C (see page 15, lines 15-20). Pharmaceutical carriers include water and sucrose solutions, which contain water (see page 4, lines 13-15, and page 6, lines 3-4). Olivieri does not comment on the size of the OMVs, but given that they are from N. meningitidis, and produced using the same process as claimed (agitation and sonication), the size is expected to fall within the range of 150-300 nm. As evidence, Roier discloses OMVs are generally between 10-300 nm in diameter (see page 2, left column, top paragraph). Therefore, the claim is anticipated by the prior art.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3, 5, 7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Olivieri et al (WO 2005/004908 A1, “Olivieri”) in view of Dai et al. (Cell, June 28, 2020, 182(3):722-733, “Dai”). The claims are summarized above and correlated with the teachings of the prior art in bold font below.
Olivieri discloses the production of OMVs from N. meningitidis (see abstract) and immunogenic compositions, including vaccines (see page 8, lines 9-11) (claim 1). The OMVs further comprise an antigen and an adjuvant, such as aluminum hydroxide or aluminum phosphate, as well as pharmaceutically acceptable excipients (see page 6, top paragraph, page 7, lines 25-26, and page 9) (claims 1, 5 and 8).
Olivieri suggests antigens generally as well as specifically, though not limiting (see page 9), but does not disclose a SARS-CoV-2 S antigen. However, it would have been obvious to have selected a SARS-CoV-2 antigen for Olivieri’s construct, given its global significance, specifically the dimeric form of SARS-CoV-2 RBD, as taught by Dai (see abstract and introduction), with a reasonable expectation of success (claims 1 and 3). Dai discloses administration of 10 µg of SARS-CoV-2 RBD dimer to mice (see Figure 3(D and E)) (claim 7). One would have been motivated to select Dai’s dimer construct because of its ability to induce neutralizing antibodies (see Dai abstract). Therefore, the claimed embodiments would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Olivieri et al (WO 2005/004908 A1, “Olivieri”) in view of Dai et al. (Cell, June 28, 2020, 182(3):722-733, “Dai”),
evidenced by Roier et al. (Nat Commun 2016, 7, 10515, 13 pages, “Roier”). Claim 6 is directed to an embodiment wherein the OMVs have a particle size in a range between 150-300 nm.
Olivieri’s teachings are outlined above. Olivieri does not comment on the size of the OMVs, but given that they are from N. meningitidis, and produced using a process that Applicant uses (agitation and sonication (see instant claim 9)), the size is expected to fall within the range of 150-300 nm. As evidence, Roier discloses OMVs are generally between 10-300 nm in diameter (see page 2, left column, top paragraph). Therefore, the claimed embodiment would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Olivieri et al (WO 2005/004908 A1, “Olivieri”) in view of Dai et al. (Cell, June 28, 2020, 182(3):722-733, “Dai”) as applied to claim 1 above, and further in view of Wang (US Patent 11,112,412 B1, filed 7/27/2020, “Wang”). Claim 2 is directed to an embodiment wherein the sequence of the antigen is SEQ ID NO: 1.
The teachings of Olivieri and Dai are outlined above. Dai discloses SARS-CoV-2 RBD but does not disclose the particular sequence instantly claimed, SEQ ID NO: 1. However, it would have been obvious to have used any SARS-CoV-2 RBD sequence for Dai’s dimer, such as Wang’s SEQ ID NO: 13, which is 100% identical in content and length to Applicant’s SEQ ID NO: 1. One would have been motivated to use Wang’s sequence, or any other SARS-CoV-2 RBD sequence, because Dai teaches that the dimer construct is applicable to any beta-CoV (see abstract). Therefore, the claimed embodiment would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claim is allowed.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Stacy B. Chen whose telephone number is 571-272-0896. The examiner can normally be reached on M-F (7:00-4:30). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas 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.
/STACY B CHEN/Primary Examiner, Art Unit 1672