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 .
Priority
This is a National Stage Entry under 35 U.S.C. 371 of International Patent Application
No. PCT/US2021/046685, filed August 19, 2021. This application also claims priority to US Provisional Application No. 63067567, filed on August 19, 2020.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-10, 12-20, and 25, and the species SEQ ID NO: 15 comprised of an amino acid sequence in the reply filed on 11/17/2025 is acknowledged. Claims 8 and 10 are drawn to a heterodimer and heterotrimer, respectively, antibody. Applicant elected species SEQ ID NO:15 for examination. Heterodimers and heterotrimers cannot be formed by identical amino acid sequences and therefore, claims 8 and 10 have been withdrawn.
Claims 2-3, 7, 10, 12-17, 19 and 23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/17/2025.
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, 4-6, 8-9, 18, 20, 22 and 25 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 1, 4-6, 8-9, 18, 20, 22 and 25 contains the trademark/trade name Nanobody®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a small antibody or a single-domain antibody and, accordingly, the identification/description is indefinite.
Claims 1, 4-6, 8-9, 18, 20, 22 and 25 are rejected on the judicially-created basis that they contain an improper Markush grouping of alternatives.
See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial structural feature and a common use that flows from the substantial structural feature for the following reasons:
MPEP 803.02 provides guidance on the analysis of a proper Markush group. Members of a proper Markush group are disclosed in the specification to possess at least one property in common which is mainly responsible for their function in the claimed relationship, and it is clear from their very nature or from the prior art that all of them possess this property. The MPEP further provides that in the members of a proper Markush group there should be (1) a common utility, and (2) a substantial structural feature essential to that utility.
In the instant case, SEQ ID NO: 1 – 81 are amino acid sequences related to VHH, SEQ ID NO: 82 – 151, are amino acid sequences related to different CDRs, SEQ ID NO: 152 – 180 are amino acid sequences related to different portions of the antibodies, SEQ ID NO: 181 – 183 are nucleic acid sequences related to portions of SARS-CoV-2, SEQ ID NO: 184 – 185 are amino acid sequence related to different portions of antibodies, and SEQ ID NO: 186 – 188 are amino acid sequences related to portions of a larger antibody. These are general groupings and do not suggest that these groupings share structural similarities.
Furthermore, the group of antibodies of the claims contain species with different CDR sets. It is well established in the art that the formation of an intact antigen-binding site of antibodies generally requires at least one variable region, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope (Paul, Fundamental Immunology, 3rd Edition, 1993, pp. 292-295, under the heading “Fv Structure and Diversity in Three Dimensions”). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the immunoglobulin. CDRs of VHH interact with each other and have sequence specific interactions that affect antigen binding.
Vu et al. (Molecular Immunology, 1997, hereinafter, “Vu”) teaches disulfide bonds between CDR1 or CDR2 and CD3 stabilize the structure the of the antigen binding site (Section: Stabilisation of long CDR3 loop by inter-CDR disulfide bond, ¶1, ¶5). Therefore, it is expected that all of the CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy variable regions is required in order to form functional antigen binding sites.
CDRs also affect the activity of antigen binding by exerting secondary changes to H1, also known as the accessible loop (Section: Importance of H1 loop in the camelid VHH antigen binding, ¶1). CDR1 overlaps with H1 and directly affects both primary binding as well as secondary features such as the rotation of antigen binding via H1 (Section: Importance of H1 loop in the camelid VHH antigen binding, ¶1, Figure 5). The variability of CDR3 affects the H1 loop, where a higher CDR3 variability increases the variability of H1, causing the binding of the antigen to occur at different angles (Section: Importance of H1 loop in the camelid VHH antigen binding, ¶4). Even small rotational differences result in large changes in affinity (Section: Importance of H1 loop in the camelid VHH antigen binding, ¶4). Therefore, it is the full set of CDRs that determines antigen binding function and so it is this set of CDRs that must match among members of a proper antibody genus. Said another way, it is the CDR set as a whole that is the substantial structural feature essential to the utility (antigen binding) of antibodies. Since the instant claims contain Markush groups with members of antibodies with differing CDR sets, the claims contain an improper Markush group and are rejected here.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(1).
Claim Rejections - 35 USC § 112- Scope of Enablement
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 25 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for inducing an immune response to a SARS-CoV-2 infection, does not reasonably provide enablement for 1) preventing a coronavirus infection in the absolute sense and 2) preventing all coronavirus infections. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” These factors include, but are not limited to:
• (A) The breadth of the claims;
• (B) The nature of the invention;
• (C) The state of the prior art;
• (D) The level of one of ordinary skill;
• (E) The level of predictability in the art;
• (F) The amount of direction provided by the inventor;
• (G) The existence of working examples; and
• (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Here, the instant claims are broadly drawn to a method for preventing a coronavirus infection by administering an antibody against the RBD of SARS-CoV-2. In regard for prevention of coronavirus infection, it is noted that the term “preventing” was interpreted in an absolute sense to mean to always keep something from happening or arising.
The claims are not enabled based on, but not limited to, two major lines of evidence. First, not all viral infection caused by SARS-CoV-2 are prevented by the antibody being claimed. And second, not all coronavirus infections are caused by SARS-CoV-2 and therefore a targeted antibody against SARS-CoV-2 would not prevent all coronavirus infections. The level of skill in the art is high and would include, e.g., Ph.D. level scientists.
The art establishes antibodies similar to those of the instant application is not 100% effecting in preventing SARS-CoV-2 infection as evidenced by Gai et al. ((biorxiv, August, 10, 2020), hereinafter, “Gai”, Figure 5). Gai evidences that antibodies have some effect on lessening SARS-CoV-2 infection but that this effect is dose dependent and even at high doses is not 100% successful at preventing a SARS-CoV-2 infection (Figure 5).
Furthermore, the art establishes that antibodies work by binding, with different efficiencies, to viral proteins from specific viruses and not all viruses (Lv et al. Cell Reports, June 2020, hereinafter, “Lv”). Lv evidenced that although cross antigen binding is common between SARS-CoV and SARS-CoV and that antibodies target both the RBD and non RBD regions, cross neutralization of live viruses is rare (Abstract, Graphical Abstract, Figure 1). Therefore, there is a reasonable expectation that an antibody that targetsSARS-CoV-2 would not prevent an infection from any coronavirus.
In view of the evidence discussed above, the antibody of claim 1 would not predictably prevent all coronavirus infections nor would it reliably prevent infections caused by SARS-CoV-2 in every single case.
The specification only exemplifies and reduces to practice lessening SARS-CoV-2 infection and symptoms following antibody administration in some cases (see, Figure 25). However, the specification offers no reasonable direction or working example for the use of antibodies that that prevent all coronavirus infections.
In view of the foregoing, a vast quantity of experimentation, including expansive clinical trials, would be needed to use the invention based on the content of the disclosure.
Taken together, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
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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/DANYAL HASSAN ALAM/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672