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
Status of the Claims
1. Claims 1-43 are the original claims filed on 5/10/2023. In the preliminary amendment of 6/5/2023, claims 1-43 are canceled and new claims 44-63 are added. In the Response of 8/3/2026, Claims 44-45, 47, 51-52, and 61 are amended, Claims 50 and 56 are canceled, and new Claims 64-66 are added.
Claim 63 is withdrawn.
Claims 44-49, 51-55, 57-62, 64-66 are all the claims under examination.
The amendment of the claims raises new grounds for rejection. The Office Action is final.
Priority
2. USAN 18/036,237, filed 05/10/2023, is a National Stage entry of PCT/EP2021/ 081303, International Filing Date: 11/10/2021, claims foreign priority to EP 21305091.7, filed 01/26/2021, claims foreign priority to EP 20306370.6, filed 11/12/2020.
The present application claims priority from EP20306370.6 and EP21305091.7. EP20306370.6 does not disclose the RBD mutations referred to in the description and in the claims of the present application and does not disclose the sequences of SEQ ID NOs: 42, 44-46, 48-53. With regard to SEQ ID NO: 42 it is noted that EP20306370.6 does disclose SEQ ID NO: 42 but this is not identical to the one of the present application, and SEQ ID NO: 44 of EP20306370.6 corresponds to SEQ ID NO: 47 of the present application. EP21305091.7 discloses said RBD mutations and discloses SEQ ID NOs: 42-46 but does not disclose SEQ ID NOs: 47-53.
The second priority date of 26-01-2021 is valid for the subject-matter related to the RBD mutations.
Information Disclosure Statement
3. AS of 9/22/2026, a total of one (1) IDS is on file: 10/9/2023. The corresponding initialed and dated 1449 form is considered and of record.
Withdrawal Objections
Specification
4. The objection to the abstract because it exceeds 150 words and contains legal phraseology (i.e., “said”) is withdrawn in view of the amended new abstract to rectify the deficiencies.
5. The objection to the disclosure because of informalities is withdrawn. Both a clean substitute and marked-up copy of the specification are filed.
a) The specification is amended to rectify the improper use of the term ATCC, Uniprot, NCBI, GraphPad, QuickPlex, Bio-Plex, EpiCoV, Live/Dead, NSG, which is a trade name or a mark used in commerce.
b) The specification is amended to correct the misspelling of “Bio-Plex.”
c) The specification is amended to correct the misspelling of “Live/Dead.”
Claim Objections
6. The objection to Claims 44-62 because of informalities is moot for the canceled claims (claims 50 and 56) and withdrawn for the pending claims.
a) Claims 44-62 are amended to recite “a receptor binding domain (RBD) polypeptide in claim 44.
b) Claims 44-49 and 57-62 are amended in claim 44 to replace the phrase “that is directed against” with “that is specific for”.
c) Claim 44 is amended to recite: “, wherein”; and to delete the phrase “at least 90% of identity with.”
d) The objection to claims 50-55 falls because claim 50 is canceled.
e) Claim 56 is canceled.
Withdrawal of Rejections
Claim Rejections - 35 USC § 112(b)
7. The rejection of Claims 45 and 51 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite.
a) Claim 45 is amended to delete the period following element (g).
b) Claim 45 is amended to include coordinating conjunctions in elements (d)-(i), e.g., insertion of “or.”
c) Claim 51 is amended to replace the phrase “derives from” with “a chimeric or humanized antibody based on the sequence of _”.
Claim Rejections - 35 USC § 112(a)
Written Description
8. The rejection of Claims 44, 46, 48-57, and 59-62 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 is moot for the canceled claims and withdrawn for the pending claims. Generic claim 44 is amended to include the alternative to the RBD consisting of amino acid residues 319-541 of SEQ ID NO: 1, being the mutated RBD amino acid residues 319-541 of SEQ ID NO: 1 containing one or more naturally occurring mutations(s) at position 417, 452, 478, 484 or 501 and a non-naturally occurring mutation at position 538.
NOTE: The amendment to the claims raises new grounds for rejection under 35 USC § 112(a) (written description) set forth below.
Claim Rejections - 35 USC § 103
9. The rejection of Claim(s) 44, 45(a), 46, 48-49, and 59-62 is/are rejected under 35 U.S.C. 103 as being unpatentable over CN 111533809 A (Wuhan Inst Virology; 8/14/2020; translation attached) in view of Hume et al (US 20210000942; published 2021-01-07) is withdrawn. Neither Wuhan nor Hume teach or suggest a conjugation- or fusion-construct comprising an anti-CD40 antibody and the RBD comprising residues 319 to 541 of SEQ ID NO: 1 (or mutations thereto).
Rejections Maintained
Claim Rejections - 35 USC § 112(a)
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.
Scope of Enablement
10. The rejection of Claim 62 under 35 U.S.C. § 112 (a), or 35 U.S.C. § 112 (pre-AIA ) first paragraph, is maintained because the specification does not reasonably provide enablement for any vaccine with any anti-CD40 antibody fused or conjugated thru the HC and/or LC to a RBD polypeptide comprising residues at positions 319 to 541 for SEQ ID NO:1 or the mutated RBD amino acid residues 319-541 of SEQ ID NO: 1 containing one or more naturally occurring mutations(s) at position 417, 452, 478, 484 or 501 and a non-naturally occurring mutation at position 538.
Applicants allege Experimental data has been obtained using such conjugates comprising an anti- CD40 antibody conjugated or fused to a native RBD polypeptide. Claimed mutations correspond to those of natural SARS-Cov2 variants. Once the usefulness as a vaccine of a conjugate using a native RBV polypeptide has been established (see Examples 1 and 2 in Applicants' Specification), one of ordinary skill in the art would have readily expected that the use of conjugates comprising RBD variants corresponding to natural SARS-Cov2 variants would also be useful for vaccination purposes.
Response to Arguments
The vaccine claim is drawn to amended claim 44 that includes a “non-naturally occurring mutation at position 538”. Thus, the claimed subject matter is dispositive to Applicants statement that “natural SARS-Cov2 variants would also be useful for vaccination purposes” where there is no showing that a non-natural mutation to the sequence of SEQ ID NO: 1 in fusion with or conjugated to a generic anti-CD40 antibody would perform comparable to a “natural variant.”
The vaccine claim is drawn to amended claim 44 that includes any mutation irrespective of being natural or non-natural to residues 417, 452, 478, 484, 501 or 538 of the sequence of SEQ ID NO: 1. The term mutation encompasses myriad amino acid manipulations and combinations taught at
[0014] As used herein, the term “mutation” has its general meaning in the art and refers to a substitution, deletion or insertion. In particular, the term “substitution” means that a specific amino acid residue at a specific position is removed and another amino acid residue is inserted into the same position. Within the specification, the mutation are references according to the standard mutation nomenclature. In particular the term “mutation” encompasses “naturally-occurring mutations” and “non-naturally occurring mutations”.
In addition, Applicants rely on Attorney arguments that are not substantiated by extrinsic evidence showing that just any anti-CD40 antibody much less in fusion or conjugation with just any SARS-Cov2 variant of claim 44 would be vaccine therapeutic and/or prophylactic for any SARS-Cov2. MPEP 716.01 and 2145 (The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)).
The Patent Act requires the applicant to describe the invention in explicit terms to enable any person skilled in the art to make and use the invention. 35 U.S.C. 112. Applicants seek over potentially millions of anti-CD40 antibodies in a fusion/conjugate with a wild-type RBD of SEQ ID NO: 1 much less with myriad mutated RBDs of SEQ ID NO: 1. The enablement requirement is a crucial aspect of the patent “bargain”: an inventor is granted limited protection from competition in exchange for publicly disclosing their new technology. See the decision in Morse, Incandescent Lamp, and Holland Furniture, establishing the requirement that if a patent claims an entire class or genus of processes, machines, or compositions of matter, the specification must enable a person skilled in the field to make and use the entire class. If a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class. In other words, the specification must enable the full scope of the invention as defined by its claims. The more one claims, the more one must enable. See §112(a); see also Continental Paper Bag Co. v. Eastern Paper Bag Co., 210 U. S. 405 (1908) (“[T]he claims measure the invention.”)
The rejection is maintained.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
11. The provisional rejection of Claims 44-49, 51-55, 57-62, 64-66 on the ground of nonstatutory double patenting as being unpatentable over claims 76-77(b), 80-84, and 88-92 of copending Application No. 17/927,804 (reference application US 20230212231) is moot for the canceled claims and maintained for the pending claims.
Applicants invocation of “MPEP 804.B.1” as a response is acknowledged but is understood to mean 804(I)(B)(1). However, the section under 804(I)(B)(1) does not address the ripeness of a provisional double patenting rejection when there are other outstanding rejections for the claims as does the case under MPEP 1490.
The response is incomplete. The rejection is maintained.
Objections Maintained
Claim Objections
12. The objection to Claim 61 because of informalities is maintained.
Claim 61 is objected to because the claim refers to two sets of claims to different features: a nucleic acid and a vector (MPEP 608.01(n)).
Appropriate correction is required.
New Grounds for Rejection
Claim Rejections - 35 USC § 112
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.
Written Description
13. Claims 44-49, 51-55, 57, 59-62, and 64-66 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.
Claim 58 is not rejected.
The vaccine claim is drawn to amended claim 44 that includes a “non-naturally occurring mutation at position 538”. There is no showing that a non-natural mutation to the sequence of SEQ ID NO: 1 in fusion with or conjugated to any generic anti-CD40 antibody would perform comparable to a “natural variant of SEQ ID NO:1.”
The vaccine claim is drawn to amended claim 44 that includes any mutation irrespective of being natural or non-natural to residues 417, 452, 478, 484, 501 or 538 of the sequence of SEQ ID NO: 1. The term mutation encompasses myriad amino acid manipulations and combinations taught at
[0014] As used herein, the term “mutation” has its general meaning in the art and refers to a substitution, deletion or insertion. In particular, the term “substitution” means that a specific amino acid residue at a specific position is removed and another amino acid residue is inserted into the same position. Within the specification, the mutation are references according to the standard mutation nomenclature. In particular the term “mutation” encompasses “naturally-occurring mutations” and “non-naturally occurring mutations”.
Applicants seek over potentially millions of anti-CD40 antibodies in a fusion/conjugate format with a wild-type RBD of SEQ ID NO: 1 or much less with myriad mutated RBDs of SEQ ID NO: 1.
The status of SARS-Cov2 spike protein variance is recognized as being unpredictable. Predicting SARS-CoV-2 spike protein variant effectiveness (neutralization escape, ACE2 binding, and functional fitness) is moderately high for short-term trends (weeks to months) but limited for long-term trajectory prediction due to complex host-pathogen epistasis and population immunity shifts (Wang et al (PTO 892) and Dadonaite et al (PTO 892)). Core issues are Inter-Individual Variation: Antigenic effects of specific mutations vary significantly across human serum cohorts. Epistasis: Mutations change fitness contextually; a harmful mutation in one background may thrive with compensatory changes elsewhere. Biases: Geographic and temporal sequencing gaps (e.g., GISAID sampling skews) reduce real-world translation accuracy.
Applicants have failed to show the existence of appropriate mutated epitopes of the spike protein (or even the wild type sequence) in combination with just any anti-CD40 antibody that would provide specific antigen binding much less possess a universal vaccine potential. The Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See University of Rochester v. G.D. Searle & Co., lnc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004). There is insufficient guidance and direction as to the written description of the claimed antibody, as broadly encompassed by the claimed invention much less in combination with the spike protein format. Given the well-known high level of polymorphism of immunoglobulins / antibodies, the skilled artisan would not have been in possession of the vast repertoire of antibodies and the unlimited number of mutated spike proteins encompassed by the claimed invention; one of skill in the art would conclude that applicant was not in possession of the functional attributes of a representative number of species possessed by the members of the genera as indicated above, and broadly encompassed by the claimed invention. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genera.
Conclusion
14. No claims are allowed.
15. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu Julie can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LYNN A BRISTOL/ Primary Examiner, Art Unit 1643
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