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 .
Status of the Claims
Claims 27-48 are currently pending in the Application and are examined on the merits below.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
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 40 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. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961)("one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. 101. (MPEP 2173.05(q)).
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.
Claim 40 is 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 40 attempts to describe a process of manufacturing a medicament in the treatment of coronavirus but does not provide any active steps of the method. Appropriate correction is required.
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.
Claims 27-48 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 27 is concerned with nanobody which are directed to the SARS-CoV-2 virus and more particularly the Spike protein which is responsible for SARS-CoV-2 viral entry into host cells through binding of its host cell receptor ACE2 . The nanobody is defined as comprising a CDR1 represented as SEQ ID NO:1 a CDR2 represented as SEQ ID NO:2 and a CDR3 thereby selected from SEQ ID Nos 40-60. The CDR1 and CDR2 may comprise anywhere from 0-4 amino acid modifications and the CDR3 may comprise from 0-7 amino acid modifications. The antibody is described as (a)-(c), affecting binding between the spike protein and ACE2, having a Kd value for spike protein of less than 20nm and a ND value for SARS-CoV-2 of less than 100nM. Thus the antibody may be potentially utilized as an anti-viral agent.
In the specification Applicant has isolated a from a phage display library a number of binding moiety (Table 1) of which one clone NbRBD_H11 was further affinity matured through a CDR3 PCR mutagenesis and further selection procedure to arrive at least 20 additional variants (table 2) as indicated above all of which share identical CDR1 and CDR2 with limited variability in the CDR3 as presented. This however is not what the Applicant claims.
Regarding the written description requirement and the claimed binding nanobody moiety, the Applicant claims a variety of mutations in the CDR1, CDR2, CDR3 regions of the disclosed SEQ ID Nos. The CDR1 and CDR2 claimed may vary by up to 4 amino acids each which represents 50% of the indicated CDR1 and CDR2 amino acid components. The CDR3 may vary by up to 7 amino acid locations, which represents 35% of each CDR3 as claimed. Interestingly it is noted that when viewing the CDR3 regions of affinity matured variants of the original H11 clone, the main differences between the variants appears in amino acids 2-7 of the variants with residue 1 and 8-20 conserved. Thus by claiming up to 7 amino acid modifications Applicant would mutate/delete or otherwise alter all of the amino acids which appear to be important for variations in binding discovered. Conversely, conserved amino acids which appear important for antigen binding are likewise potentially altered (residue 1, 8-20). These modifications may be combined with additional modifications to the accessory binding regions of the CDR2 and CDR1 of the antigen binding molecule. Thereby Applicant claims a large genus of binding molecules which Applicant attempts to restrict to only those which satisfy the functional characteristics which are presented in (a)-(c) of the claim 27. Applicant provides a limited representative sample of 20 species of the claimed genus as explained above.
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 applicant was in possession of the claimed genus. See MPEP 2163(II)(A)(3)(a)(ii).
For an example of the complexity, diversity, and unpredictability of antigen binding derived from antibody molecules one can look to the disclosure of Rabia (Biochemical Engineering Journal 137 (2018) 365–374), which teaches that the maximal chemical diversity of antibody CDRs is unimaginably large and is extremely challenging to define the sequence determinant of antibody specificity (see page 4). Rabia also teaches that single point mutations in CDR regions can alter binding specificity, and that such mutations are highly context dependent, and the same mutations can lead to opposite impacts on antibody specificity in different antibody sequences (see page 5, in particular).
For further example of the complexity, diversity and unpredictability of binding derived from antibody-protein interactions one may look to the disclosure of Lloyd et al. (Protein Engineering, Design & Selection vol. 22 no. 3 pp. 159–168, 2009).With respect to viable binding molecules (antibody) to a particular antigen (protein), Lloyd illustrates the tremendous diversity of VH and VL pairings and also usage of diverse repertoire of the highly variable antibody VH and VL sequences corresponding to what amounts to a diverse variable and unpredictable mix of amino acid sequences which bind to antigen through protein-protein interactions. (see Lloyd fig 1, 2, and p167 paragraphs 1-2).
Thus describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene "because it is only an indication of what the gene does, rather than what it is."); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product; however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that "[w]without such disclosure, the claimed methods cannot be said to have been described."(MPEP 2163 II.A.3(a) paragraph 6).
Therefore the application at best describes a roadmap for producing candidate targeting moieties by picking and choosing from wide range of CDR regions combinations, and then screening to determine which actually function to bind the SARS-COV-2 spike protein. Applicant provides a limited clustered group of representative species, while claiming a large and unpredictably diverse group of antigen binding nanobodies. Therefore one of skill in the art would conclude that the Applicant was not in possession of the broad genus of mutated nanobody and method which utilize said nanobody as are instantly claimed.
Conclusion
Summary: No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Reference 28 IDS filed 06-21-2023 discloses camelid VHH antibodies which bind to spike protein of the SARs-COV-1 coronavirus with a neutralizing effect. The antibody likewise cross-react with SARS-COV-2 coronavirus spike protein with neutralizing effect on ACE2 receptor binding (abstract, throughout). However the VHH sequences of interest are not the same as the instant claimed sequences with recognition of divergent epitope of the spike protein (supplementary figure 2).
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/BRIAN HARTNETT/ Examiner, Art Unit 1644
/DANIEL E KOLKER/ Supervisory Patent Examiner, Art Unit 1644