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 .
Election/Restrictions
Applicant’s election without traverse of Group I, corresponding to claims 1 – 8 in the reply filed on 04/30/2026 is acknowledged.
Claims 9 – 20 are withdrawn from further consideration pursuant to 37
CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or
linking claim.
Claims 1 – 8 are under examination.
Priority
This application claims priority to US provisional application 63487164, filed on February 27, 2023 and to US provisional application 63382752, filed on November 08, 2022.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings. Figures 1, 6, 9, and 12 contain sequences that are not accompanied with sequences identifiers (i.e., “SEQ ID NO:X).
Required response – Applicant must provide:
Amended 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 (i.e., “SEQ ID NO:X” or the like) 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 Figures 1, 4, 6, 9, and 12 are not of sufficient quality. 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 Rejections - 35 USC § 112 – Written Description
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.
Claim 5 is 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 written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010); University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) at 1406; Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ("[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568,43 USPQ2d l398, 1406 (Fed. Cir. 1997). The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. Further, the Court held that to adequately describe a claimed genus, an applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.”
Instant claim 5 broadly encompasses a SARS-CoV-2 antibody or antigen-binding fragment thereof according to claim 1 and a second isolated SARS-CoV-2 antibody or antigen-binding fragment there of that binds specifically to the SARS-CoV-2 antigen, where the first and second antibodies bind to different epitopes of the SARS-CoV-2 antigen and the two exhibit a synergistic effect in neutralizing SARS-CoV-2 variants.
The Specification has failed to sufficiently describe the structural features that must be retained by members of the claimed genus as to establish a structure-function relationship with respect to the ability of the antibody-binding protein to bind a SARS-CoV-2 antibody The claims define the protein based on it does—not what it is. Additionally, the Specification has failed to sufficiently describe the structural features that must be retained by members of the claimed genus as to establish a structure-function relationship with respect to the combination of antibodies exhibiting a synergistic effect in neutralizing SARS-CoV-2 variants.
The claim recites a “second isolated SARS-CoV-2 antibody or antigen-binding fragment there of that binds specifically to the SARS-CoV-2 antigen” which alone encompasses a large amount of proteins as there are no structural limitations assigned to the protein and does not establish a structure-function relationship with the ability to bind to SARS-CoV-2 antigen. While the claim does give a vague limitation of the second antibody or antigen-binding fragment binding to a different epitope of SARS-CoV-2 than the first clearly defined antibody, this limitation does not impart enough structure to establish a structure-function relationship. As such, the claim describes a countless amount of antibodies and antigen-binding fragments. Furthermore, not every antibody that fits the vague description of the second antibody will have synergistic effects. It is unclear which structural limitations must exist for there to be a synergistic effect towards neutralizing SARS-COV-2 in combination with the well-defined antibody or antigen-binding fragment of claim 1.
While the instant claims are drawn to a genus that comprises innumerable number of antibodies, the Specification has only adequately described and successfully reduced to practice 9 antibodies and, importantly, has only reduced to practice the synergistic effect of two antibodies named Acovimab and Sotrovimab (Figure 8, 10, and 11). However, this is not representative of the extremely large genus of antibodies claimed.
The data generated for the select antibodies described in the Specification and Drawings cannot reasonably be extrapolated and applied to support possession of the entire claimed genus of antibodies and antigen-binding fragments thereof because no second antibody or combination of first and second antibody accounts for the structure or synergistic effects amongst the claimed genus. As in Ariad, merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species. “A patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.” Brenner v. Manson, 383 U.S. 519, 536 (1966).
Moreover, Rudikoff et al (PNAS, 1982, hereinafter, “Rudikoff”) teaches that highly similar antibody structures do not result in predictable function. Rudikoff teaches the CDR plays a key role in the target affinity of an antibody, showing that even a single amino acid alteration in the CDR can result in loss of antigen-binding function (Section: Implications for Generation of Diversity). Because the properties and function of an antibody are highly dependent upon the amino acid sequences and exact combination of CDRs, wherein, even one amino acid difference in a CDR region leads to different functional properties, different conformations of CDR sequences would result in antibodies or antigen-binding fragments having different properties. Furthermore, Einav et al (bioRxiv, 2020, hereinafter, “Einav”) teaches models of antibody mixtures through simulation. Einav teaches that even though models can be used to account for to help predict the activity of antibody mixtures, it can be “difficult to predict how antibodies will behave when mixed together, even after each has been independently characterized” (Abstract). Thus, when taken with the teachings of Rudikoff and Einav, one of skill in the art would readily appreciate that mere knowledge of structure alone cannot serve as the basis to describe members of the genus that have the recited function because a single antibody’s structure is unpredictable, let alone when combined with other antibodies of similar structure.
In the absence of a representative number of examples, the Specification must at least
describe the structural features that are required for the claimed function, in this case binding to a different epitope of SARS-CoV-2 compared to the antibody of claim 1 and exhibiting synergetic effects when paired with the antibody of claim 1. However, as discussed above, the Specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to SARS-CoV-2 epitope binding activity. The Specification also fails to describe which regions, domains, etc. of the antibody sequences must be retained in order to have a neutralizing effect of SARS-CoV-2 variants. Instead, Applicant merely offers a cursory statement that any antibody or antigen-binding fragment that binds to a SARS-CoV-2 epitope will work.
Accordingly, the claims as currently written are not adequately described and one of skill in the art would readily appreciate that Applicant was not in possession of the claimed genus at the time of filing.
Claim Rejections - 35 USC § 112 - Indefiniteness
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 – 8 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.
Regarding claims 1- 8, the transitional phrase “having” is unclear as to whether open or closed claim language is intended. The variable regions of the antibody may be defined by the exact SEQ ID NO: 7 and 8 or may be comprised of SEQ ID NO: 7 and 8. See MPEP 2111.03 (IV). For purposes of compact prosecution and examination, “having” is interpreted as “comprising”.
Regarding claims 1 – 8, there are no CDRs defined by a CDR labeling system, thus rendering the claim indefinite. The claims could read on Kabat, IMGT, or Chothia CDRs, for example, giving multiple structural interpretations. The claims could also read on composite CDRs such as those including both Kabat and IMGT CDRs. The claim may also allow mixing and matching from multiple labeling systems, some from Kabat, some from IMGT, etc. The presence of so many different interpretations render the claims indefinite.
Regarding claims 1 – 3, HCDR1 defined by SEQ ID NO: 1 is not found in the heavy chain variable region defined by SEQ ID NO: 7. It is unclear if HCDR1 is an animo acid sequence found in the heavy chain variable region of claim 1 and 3 or whether the heavy chain variable region comprises a different CDR that is not encompassed in claim 2. SEQ ID NO: 1 is an amino acid sequence comprising “GFTFTGT”, however SEQ ID NO: 7 does not contain this exact amino acid sequence. The closest match within SEQ ID NO:7 to SEQ ID NO: 1 is “GFTFTTT” (Reproduced below). There is a mismatch at amino acid in position 31 of SEQ ID NO: 7.
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Claim Rejections - 35 USC § 112 - Dependence
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2 – 4 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. As discussed above, HCDR1 defined by SEQ ID NO: 3 is not found in the heavy chain variable region defined by SEQ ID NO: 7 and therefore it is unclear whether the heavy chain variable region comprises a different CDR that is not encompassed in claim 2. Furthermore, claim 3 does not further limit any aspect of claim 2 because claim 1 already defines the heavy and light chain variable regions by SEQ ID NO: 7 and 8 respectively.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
NO CLAIMS ARE ALLOWED
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas J. Visone can be reached at 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DANYAL HASSAN ALAM/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
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