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 .
Claims 1-28, of record 12/26/2024, are pending and subject to prosecution.
Priority
The instant application is a national stage entry of PCT/GB2022/053351 (filed 12/21/2022). Acknowledgement is made of the applicant’s claim for foreign priority to UK application 2118685.3 (filed 12/21/2021).
Nucleotide and/or Amino Acid Sequence Disclosures
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). All sequences longer than ten nucleotides or four amino acids referenced in the specification must include a SEQ ID NO and must be included in the Sequence Listing. MPEP 2422.02 requires "that when a sequence is presented in a drawing, regardless of the format or the manner of presentation of that sequence in the drawing, the sequence must still be included in the Sequence Listing and the sequence identifier ("SEQ ID NO:X') must be used, either in the drawing or in the Brief Description of the Drawings." See MPEP 421-2422.
Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings; fig. 2-3 have amino acid or nucleic acid sequences that are not accompanied by SEQ ID NO in the figure or in the specification.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Drawings
The drawings are objected to because each sheet must include a top margin of at least 2.5 cm. (1 inch), a left side margin of at least 2.5 cm. (1 inch), a right side margin of at least 1.5 cm. (5/8 inch), and a bottom margin of at least 1.0 cm. (3/8 inch). See 37 CFR 1.84(g). 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.
Additionally, the drawings of 6/20/2024 are objected to because the drawings contain nucleotide and amino acid sequences that are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). All sequences longer than ten nucleotides or four amino acids referenced in the specification must include a SEQ ID NO and must be included in the Sequence Listing. MPEP 2422.02 requires, "that when a sequence is presented in a drawing, regardless of the format or the manner of presentation of that sequence in the drawing, the sequence must still be included in the Sequence Listing and the sequence identifier ("SEQ ID NO:X') must be used, either in the drawing or in the Brief Description of the Drawings." See MPEP 2421-2422.
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.
It is noted that this office action comprises both an objection to the Nucleotide and/or Amino Acid Disclosure AND an objection to the Drawings. Applicant need only either amend the specification at the Brief Description of the Drawings section OR provide amended drawings to overcome both objections. Applicant does not need to do both.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in ¶0356-0357 of the instant application’s PG Pub. 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.
The use of the terms Tween, GeneArt, Benzonase, Opti-MEM, Alexa Fluor, TrypLE, Prism, GraphPad, and EVOS, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 5, 7-16, 18-20, 23, and 25-27 are objected to because of the following informalities:
Claims 5, 7-16, 18-20, 23, and 25-27 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP 608.01(n).
Appropriate correction is required.
Claim Interpretation
Multiple dependent claims 3-5, 7-15, 18-20, 23, and 25-27 are interpreted as depending from independent claim 1, in the interest of compact prosecution. Multiple dependent claim 16 is interpreted as depending from independent claim 2.
In claims 4-5, 11, 14, 16-17, 19, 25, and 28, preferred embodiments are interpreted as being optional.
Claim 11 recites the limitation ”wherein the modified spike protein is not detected by anti-coronavirus spike protein antibodies”. The broadest reasonable interpretation of this limitation is a spike protein that is not capable of being bound by any antibodies having binding affinity to any coronavirus family spike proteins.
Claim 27 recites the limitation “lentiviral envelope components”, which is not defined by the instant specification. The broadest reasonable interpretation of this limitation is therefore considered to be the env gene or a fragment thereof.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 26 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim does not fall within at least one of the four categories of patent eligible subject matter because “use” claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101.
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 1-28 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.
Independent claims 1-2 recite the limitation “the cytoplasmic tail” in line 6. There is insufficient antecedent basis for this limitation in the claims. Dependent claims 3-28 are included in the rejection.
Claim 4 recites, “The lentiviral vector of any one of the preceding claims 1…”. It is unclear whether the claim is intended to depend from claim 1 or from any of claims 1-3.
Regarding claims 4-5, 11, 14, 16-17, 19, 25, and 28, the term “preferably” renders the claims indefinite because it is unclear whether the limitation(s) following the term are part of the claimed invention. See MPEP 2173.05(d).
Claim 26 recites a use but fails to describe any active, positive steps delimiting how the use is practiced. The claim is indefinite because it attempts to claim a process without setting forth any steps involved in the process.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1-8, 10, 12, 15-18, and 20-26 are rejected under 35 U.S.C. 103 as being unpatentable over Caruso (WO 2022051859 A1) in view of Dinnon et al. (Nature, 2020).
Regarding claims 1-2, 4-8, 12, 15-17, 20, and 24-26: Caruso teaches pseudotyped VLPs derived from a retroviral vector and comprising a SARS-CoV-2 spike protein (See Abstract). The retroviral vector can be lentiviral (See ¶0016). The VLPs can express GFP under the control of the 5 ’LTR (which reads on “a transgene operably linked to a promoter”) in infected cells (See ¶00103 and 00124 and fig. 4A-B and 6A-B). Caruso teaches a spike protein consisting of an amino acid sequence identical to instant SEQ ID NO 1 (See ¶0015, SEQ ID NO 1, and alignment below (first 120 aa displayed).
PNG
media_image1.png
222
622
media_image1.png
Greyscale
The spike protein can comprise a D614G mutation (which reads on “mutations at amino acid positions corresponding to, or aligning with, positions… 614 of SEQ ID NO: 1”, “amino acid substitutions”, and “non-conservative amino acid substitutions”) (See ¶00113 and 00123). The cytoplasmic tail of the spike protein can be truncated, such as by a 19-aa deletion (which reads on “deletion of at least a portion of the cytoplasmic tail” and “deletion of at least 10 amino acids”) (See ¶0073 and fig. 1). Caruso does not teach mutations at positions 488-499 of the spike protein.
Dinnon et al. teach a mouse-adapted model of SARS-CoV-2 (See Abstract). The SARS-COV-2 spike protein was modified to comprise Q498Y and P499T mutations in order to promote entry via murine ACE2 (See page 561, col. 1, full ¶1-2).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the spike protein of the VLP of Caruso to comprise the mutations taught by Dinnon et al. One would have been motivated to make this modification because Dinnon et al. teach that it enables viral pathology and treatments to be studied in mice or mouse cells (See Abstract). There would be a reasonable expectation of success in making this modification because one of ordinary skill could readily generate point mutations in the construct of Caruso. The spike protein resulting from the combined teachings of Caruso and Dinnon et al. comprises a sequence identical to instant SEQ ID NO 13 and a sequence 99.9% identical to instant SEQ ID NO 20 (See alignments below (first 120 aa displayed)).
PNG
media_image2.png
224
618
media_image2.png
Greyscale
PNG
media_image3.png
222
616
media_image3.png
Greyscale
Regarding claim 3: Following the discussion of claims 1-2, 4-8, 12, 15-17, 20, and 24-26, Caruso does not expressly teach the residues in the spike protein that the cytoplasmic tail encompasses. However, Caruso teaches a SARS-CoV-2 sequence (See ¶0015, SEQ ID NO 1) identical in sequence and length to instant SEQ ID NO 1, which the instant specification teaches as comprising a cytoplasmic tail corresponding to residues 1235-1273 (See ¶0147 of the application’s PG Pub).
Regarding claim 10: Following the discussion of claims 1-2, 4-8, 12, 15-17, 20, and 24-26, Caruso teaches that the spike protein can be encoded by a codon-optimized Wuhan-Hu-1 isolate (See ¶00123).
Regarding claim 18: Following the discussion of claims 1-2, 4-8, 12, 15-17, 20, and 24-26, Caruso does not expressly teach the VLP as being derived from an HIV vector. However, Caruso teaches that VLPs have been successfully produced from viruses including HIV (See ¶0050). One of ordinary skill in the art would have therefore found it obvious to use HIV as the lentiviral vector.
Regarding claims 21-23: Following the discussion of claims 1-2, 4-8, 12, 15-17, 20, and 24-26, Caruso teaches that the VLPs can be generated by transfecting host cells with a pMD2 plasmid (which reads on “a polynucleotide molecule” and “expression construct comprising the polynucleotide… operably linked to a promoter”) encoding the spike protein, infecting the cells with a retroviral vector, and harvesting the supernatant containing the VLPs (See ¶0062).
Claims 1-10, 12, and 15-26 are rejected under 35 U.S.C. 103 as being unpatentable over Caruso (WO 2022051859 A1) in view of Dinnon et al. (Nature, 2020), further in view of Jackson et al. (Biochemical and Biophysical Research Communications, 2021).
The teachings of Caruso and Dinnon et al. are set forward in the rejection above and are incorporated herein in their entirety.
Regarding claims 9 and 19: Following the discussion of claims 1-8, 10, 12, 15-18, and 20-26, Caruso, modified by Dinnon et al., does not expressly teach or suggest that a SARS-CoV-2 spike protein comprising Q498Y, P499T, and D614G mutations is capable of binding the human ACE2 enzymatic domain or transducing rodent cells. However, Dinnon et al. teach that the Q498Y and P499T mutations permit entry and replication of the virus in human cells and within mice via ACE2 (which necessarily reads on “”capable of binding to the enzymatic domain of human angiotensin converting enzyme 2”) (See page 561, col. 1, full ¶1 and fig. 2-3).
Jackson et al. teach that the D614G mutation in the spike protein is located outside of the receptor binding domain and does not affect binding affinity for ACE2 (See Abstract). SARS-CoV-2 bearing the D614G mutation was also capable of infecting hamsters (which read on “rodent cells”) (See page 110, col. 1, full ¶1-2).
Based on the teachings of Dinnon et al. and Jackson et al. regarding the impact of individual mutations, one of ordinary skill in the art would have reasonably expected the lentiviral VLP bearing a SARS-CoV-2 spike protein with Q498Y, P499T, and D614G mutations to be able to bind ACE2 and infect human and rodent cells.
Claims 1-8, 10, 12-18, and 20-26 are rejected under 35 U.S.C. 103 as being unpatentable over Caruso (WO 2022051859 A1) in view of Dinnon et al. (Nature, 2020), further in view of Tian et al. (eLife, 2021).
The teachings of Caruso and Dinnon et al. are set forward in the rejection above and are incorporated herein in their entirety.
Regarding claims 13-14: Following the discussion of claims 1-8, 10, 12, 15-18, and 20-26, Caruso, modified by Dinnon et al., does not expressly teach or suggest that a SARS-CoV-2 spike protein comprising a N501Y mutation.
Tian et al. teach that the N501Y mutation in the SARS-CoV-2 spike protein, which is associated with increased infectivity, strengthens binding of the virus to ACE2 (See Abstract and fig. 2-3).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to further modify the spike protein in the VLP rendered obvious by Caruso, modified by Dinnon et al., to comprise a N501Y mutation, as taught by Tian et al. One would be motivated to make this modification for functional studies of a clinically relevant mutation, and such a modification could be readily performed.
Allowable Subject Matter
Claims 11 and 27-28 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
The Examiner is not aware of any SARS-CoV-2 spike proteins, modified or not, that are unable to be bound by any anti-coronavirus spike antibodies. Additionally, one of ordinary skill in the art would not have found it obvious to include a nucleic acid sequence encoding lentiviral env or a fragment thereof when pseudotyping a lentiviral vector in order to avoid phenotypically-mixed particles with reduced display of the spike protein due to the presence of lentiviral GP.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER S SPENCE, whose telephone number is (571)272-8590. The examiner can normally be reached M-F 8:30-5:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher M Babic, can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JENNIFER S SPENCE/Examiner, Art Unit 1633
Prosecution Insights