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 .
Formal Matters
A phone call was initiated by the Examiner on 05Jun2026 because the species election appeared to contain a typo in the HCDR1-3 sequence identifiers. Attorney of Record Jing Liu (Reg. No. 62,377) confirmed in the telephone call on 05Jun206 that the election of “HCDR3: SEQ ID NO: 110” in Remarks filed on 10May2026 was a typographical error and the election should read “HCDR33: SEQ ID NO: 108”.
Claims Status
The Amendment filed on 10May2026 is acknowledged in which claim(s) 3-24, 26-57, 59, 62, 64-65, 67-70, and 75-76 were canceled, and claim(s) 81-82 are new.
Applicant’s election without traverse of Group I and a species of (a) HCDR1: SEQ ID NO: 44, HCDR2: SEQ ID NOL: 76, and HCDR3: SEQ ID NO: 108 (see formal matters above for details), and (b) VL: SEQ ID NO: 173 in the reply filed on 10May2026 is acknowledged.
Claim(s) 25 and 77-80 is/are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10May2026.
Claim(s) 1-2, 58, 60-61, 63, 66, 71-74, and 81-82 is/are currently pending and presented for examination on the merits.
Drawings
The drawings are objected to because:
figs. 1-2 : text is not clearly legible.
figs. 6-7: Unclear which line corresponds to which antibody.
fig. 15, 17, 19: the lightest text of each legend is/are not clearly legible.
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.
Claim Interpretation
Claim(s) 58 recite(s) “… is an scFab..and comprises a scFab linker, and wherein the scFab linker comprises an amino acid sequence adapted to present CDR-H1, CDR-H2…” in line(s) 2-4. A skilled artisan would understand that any scFab linker would need to allow proper presentation of the VH and VL CDRs for binding. Therefore, teachings in the prior art of any scFab and/or comprising an scFV fragment (e.g., VH-linker-VL) comprising a will be considered to meet the above limitations regarding comprising a linker and being “adapted to present 6 CDRs”.
Claim Objections
Claim(s) 58 is/are objected to because of the following informalities:
Missing an ‘and’ between “CDR-L2” and “CDR-L3” in line 4.
The abbreviation “RBD” in line 5 should be defined before use.
Appropriate correction is required.
Claim(s) 81-82 is/are objected to because of the following informalities: “comprising” is grammatically incorrect. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 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.
Claim(s) 1-2, 58, 60-61, 63, 66, 71-74, 81-82 is/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(s) 1, 60-61, 63, 66, 71-74, 81-82, recite(s) “…(VH) region comprising: (a)…;(b)…;(c)…; and/or a light chain variable region (VL) comprising…” in line(s) 3-13, rendering the claim(s) indefinite. Specifically, the lack of joining word (e.g., ‘and’; ‘or’) between 1(a) and 1(c) makes it unclear if the phrase means the VH domain comprises (1) only one HCDR (e.g., HCDR1 or HCDR2 or HCDR3); (2) two HCDRs (e.g., HCDR1-2); (3) HCDR1-3; or (3) something else. For the purposes of compact prosecution, the phrase will be considered to be joined by an “or”. This rejection may be overcome by amending claim(s) 1 to recite ‘and’ between 1(a) and 1(c). Claim(s) 60-61, 63, 66, 71-74, and 81-82 can overcome this rejection by amending claim(s) 1 as recited above.
Claim(s) 1-2, 58, 60-61, 63, 66, 71-74, 81-82, recite(s) “light chain variable region (VL) comprising…[elected SEQ ID NO: 173]” in line(s) 13-16 of claim(s) 1, and line(s) 1-2 of claim(s) 81-82, rendering the claim(s) indefinite. The instant disclosure provides that SEQ ID NO: 173 corresponds to the entire light chain [e.g., ¶ 0025, 0200, 0214]. A skilled artisan would understand that a light chain comprises a VL and a CH domain. Therefore, the claim is indefinite because it recites a VL comprising a full light chain, which is not possible. For the purposes of compact prosecution, the phrase is considered to be “a light chain comprising SEQ ID NO: 173, wherein the light chain comprises a light chain variable region (VL)”. This rejection may be overcome by amending claim(s) 1, 81-82 as recited above or to otherwise clearly recite the limitation(s) of the instant invention. Claim(s) 58, 60-61, 63, 66, and 71-74 can overcome this rejection by amending claim(s) 1, 81-82 as recited above.
Claim(s) 58, 63, 71-72, recite(s) “of claim 21” in line(s) 1, rendering the claim(s) indefinite. Claim 21 was canceled by the Applicant, therefore the scope of the invention is unclear. For the purposes of compact prosecution, claim(s) 58, 63, 71-72 will be considered to depend from claim 1. This rejection may be overcome by amending claim(s) 1 as recited above or to otherwise depend from an existing claim.
Regarding claim(s) 71, the phrase "optionally" in line 4 renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(h)(II). It is unclear if the limitation(s) following the phrase are limitation(s) or merely provided as an example. For the purposes of compact prosecution, the limitations following the phrase are not considered part of the claimed invention. This rejection may be overcome by amending claim(s) 71 to remove “optional” limitations and/or the phrase “optionally”.
Claim Rejections - 35 USC § 112(a) – written description
Claim(s) 1-2, 58, 60-61, 63, 66, 71-74, 81-82 is/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.
Claimed Invention
Claim(s) 1-2, 58, 60-61, 63, 66, 71-41, and 81-82, are drawn to an antibody or antigen binding fragment thereof that binds sarbecovirus.
Breadth of Claims
The invention as disclosed in claim(s) 1 (and dependent claim(s) 2, 60-61, 63, 66, 71-41, 81-82) are readable to 1 or 3CDRs, which is effectively half of an antibody binding site, as being sufficient for a functional antibody binding region. Specifically, the claim limitations as written require only one (I) HCDR (e.g., HCDR2 only) or (II) VL comprising 3 CDRs (e.g., LCDR1-3), which is effectively (I) less than half or (II) half an antibody binding site, respectively, missing either the (I) HCDR complement (e.g., HCDR1 and HCDR3) and the VL complement comprising LCDR1-3, or (II) the VH complement comprising HCDR1-3 that would create the full antibody binding site (e.g., 6 CDRs). One of ordinary skill in the art would understand that one cannot use (I) less than half or (II) half of an antibody binding domain (e.g., HCDR3 only; VL only; etcetera) and reasonably expect to maintain sarbecovirus antigen binding function.
The invention as disclosed in claim(s) 1 (and dependent claim(s) 2, 58, 60-61, 63, 66, 71-41, 81) recite(s) “…(VL) comprising…an amino acid sequence differing by one or two mismatches relative to a sequence selected from any one of SEQ ID NOs: [elected species is SEQ ID NO: 173]”; claim(s) 60-61 recite(s) “… or a variant thereof having a single substitution, deletion or insertion from SEQ ID NOs…” in line(s) 3 in claim 60 and line(s) 3-4 in claim 61; and claim(s) 81 recite(s) “..(VL)…amino acid sequence differing by one mismatch relative to the sequence of SEQ ID NO: 173”. The claim(s) encompass a genus of light chain variable regions comprising variability (e.g., one or two mismatches) in the light chain variable regions which are claimed as having the function of specifically binding to sarbecovirus. This means that the variability in sequence identity can also occur in the CDRs, the domains that are critical for the antibody binding to its target, which one of ordinary skill in the art would understand to result in unpredictable binding characteristics with no reasonable expectation of maintaining sarbecovirus antigen binding. Additionally, the instant disclosure does not provide a structure-function correlation that would allow for a person of ordinary skill in the art to envision what variation can occur in the light chain, particularly in the CDR regions, such that the obtained structure would result in the claimed functions.
Scope of Disclosed Species
Light chain comprising LCDR1-3 [e.g., ¶ 0212]:
PNG
media_image1.png
148
669
media_image1.png
Greyscale
HCDR1-3 sets [e.g., ¶ 0205]:
PNG
media_image2.png
154
678
media_image2.png
Greyscale
PNG
media_image3.png
536
674
media_image3.png
Greyscale
The anti-sarbecovirus antibodies in the Applicant disclosure (see summary table above for details) with 100% sequence identity in the CDR regions of the heavy and light chain variable regions represents the anti-sarbecovirus antibodies that the applicant was in possession of at the time of filing.
State of the Prior Art
At the time of filing, antibody functionality were known to depend on the entire structure, particularly a full complement of six CDRs. It is understood by one of ordinary skill in the art that that mutation to CDRs is unpredictable and that each construct requires function testing.
Sela-Culang, Kunik, and Ofran (Fron. Immuno., Vol. 4, Article 302, Oct. 2013), hereinafter “Sela-Culang”, reviews the structural basis of antibody-antigen recognition in the state of the art. Naturally occurring antibodies have six hypervariable loops are commonly termed complementary determining regions (CDRs) and are widely assumed to be responsible for antigen recognition [e.g., pg. 1, abstract; pg. 3, “The Role of CDRs and their Definition”]. A person of ordinary skill in the art would understand that although the above basics of antibody-antigen binding are known, that the specifics of antibody structure (e.g., within the CDRs) that underlie the antigen recognition are not well characterized [e.g., pg. 1, “The Motivations for…”].
Further, Herold et al. (Nature Scientific Reports, 7:12276, 25 Sep 2017), hereinafter “Herold”, teaches that it should be emphasized that there is no correlation between experimentally determined change in antibody binding affinity and a given mutation and additionally that no such correlation is expected because antigen binding is “affected by each CDR loop differently” and changes thereto “can in principle affect antigen binding affinity in an unpredictable way” [e.g., pg. 14, ¶ 2]. Further, Herold asserts that multiple determinants regulate antigen affinity and the interactions with CDRs are complex [e.g., pg. 14, ¶ 3].
At the time of filing, WO 2022/170126 A2 (hereinafter “WO126”) taught anti-SARS-CoV-2-S (e.g., a type of sarbecovirus) antibodies were recognized in the art, and used for diagnosis, assessment, and treatment of diseases and disorders associated with coronaviruses [e.g., title, abstract]. WO126 taught various separate species of anti- SARS-CoV-2-S antibodies [e.g., “Summary”; Appendix A]. Therefore, the prior art demonstrates that the binding of SARS-CoV-2-S antigen(s) is possible by various anti- SARS-CoV-2-S antibodies. The prior art does not teach a known structure activity relationship for HCDR1-3 and LCDR1-3 in anti- SARS-CoV-2-S antibody that would allow prediction of CDR residues that specifically bind to SARS-CoV-2-S (e.g., sarbecovirus) antigen.
Thus, making changes to the CDR sequence (e.g., ‘mismatches’) of an antibody sequence and/or using only part (e.g., HCDR1 only; VL only; etcetera) of an antibody sequence is a highly unpredictable process and one skilled in the art could not a priori make any predications regarding such changes with any reasonable expectation of success nor envisage the breadth of structurally unrelated CDR combinations that would still possess the required function(s).
Conclusion
As indicated by the art, a full complement of 6 CDRs are required for antigen binding and one cannot predict which CDR residues may be changed and still result in an antibody that binds sarbecovirus. Written description can be met if the claims recite the minimal structure that is needed to perform the function recited in the claims. Above, the art indicates that the 6 CDRs in an antibody antigen-binding domain are the minimal structure that binds to a target antigen. Specifically, Applicant claim(s) 1 would need to recite and require all 6 CDRs (e.g., HCD1-3 and the light chain; or HCDR1-3 and the VL; or HCDR1-3 and LCDR1-3) in the antibody that bind sarbecovirus antigen, without variability in the CDR sequences thereof; and claim(s) 81 would need to (1) remove any reference(s) to mismatches; or (2) specify LCDR1-3 by SEQ ID NOs. and make clear in the claim language that the claimed ‘mismatches’ relative to SEQ ID NO: 173 do not occur in the CDRs. Claim(s) 2, 58, 60-61, 63, 66, and 71-74 can overcome this rejection by amending claim(s) 1 as described above.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1, 58, 63, 71, 73-74 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2022/17012 6A2 (hereinafter “WO126”).
Regarding instant claim(s) 1, 63, 71, WO126 teaches an anti-SARS-CoV2 (e.g., a sarbecovirus) antibody clone “ADI-63069”comprising a VH domain comprising SEQ ID NO: 5151 [e.g., title, abstract; ¶ ; Appendix A, tbl. 1, pg. 222, row 1 ], which has 100% sequence identity to the instant claimed HCDR2 of SEQ ID NO: 76 (see alignment below). WO126 further teaches that the instant invention binds to the spike protein of a coronavirus [e.g., ¶ 10].
Alignment of instant claimed HCDR1-3 (SEQ ID NOs: 44, 76, 108, respectively) with WO126 (SARS-CoV-2-S antibody partial amino acid sequence, SEQ ID 5151):
PNG
media_image4.png
407
1098
media_image4.png
Greyscale
Regarding instant claim(s) 58, WO126 further teaches that the antibodies of the invention (e.g., including clone ADI-63069) comprise an scFv and embodiments wherein the antibody (e.g., the scFv) further comprises a Fab constant region (e.g., scFab) [e.g., ¶ 41, 162].
Regarding instant claim(s) 73, WO126 further teaches a pharmaceutical composition comprising the anti-SARS-CoV-2-S antibody and a pharmaceutically acceptable carrier or excipient [e.g., ¶ 63].
Regarding instant claim(s) 74, WO126 further teaches a polynucleotide encoding the anti-SARS-CoV-2-S antibody [e.g., abstract; ¶ 142-143, 151].
Free From the Prior Art
During the course of examination, the anti-sarbecovirus antibody and/or antigen binding fragment(s) thereof comprising (1) HCDR1-3 of SEQ ID NOs: 44, 76, 108, respectively and (2) a light chain (e.g., comprising a VL comprising LCDR1-3) of SEQ ID NO: 173, was/were found to nonobvious in view of the closest prior art. Briefly, a sequence search of the prior art returned no 100% matches to the instant claimed HCDR1-3 (see closest prior art alignment below), and therefore cannot return a 100% sequence match to the instant claimed antibody and/or antigen binding fragments thereof.
Alignment of anti-sarbecovirus HCDR1-3 (SEQ ID NO: 44, 76, 108, respectively) with WO2022159839-A1 (Anti-S protein Mab VH region, SEQ ID 1101):
PNG
media_image5.png
234
620
media_image5.png
Greyscale
Conclusion
No claims are currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M CHATTIN whose telephone number is (571)270-0646. The examiner can normally be reached T-F 0600-1600 PST.
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, Julie Wu 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.
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.
/AMY M. CHATTIN/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643
Prosecution Insights