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 of Group I, claims 1-3, 5-7, 10, 12, 14, 15, 17-19 and 24-26 drawn to a composition, in the reply filed on 11/04/2025 is acknowledged. In Addition, Applicant’s election of the following species:
SEQ ID NO:3 in claim 3 (a)
SEQ ID NO:4 in claim 3 (b)
SEQ ID NO:3 and SEQ ID NO:4 in claim 3 (c)
SEQ ID NO:12 in claim 7 (a)
SEQ ID NO:14 in claim 7 (b)
SEQ ID NO:12 and SEQ ID NO:14 in claim 7 (c)
SEQ ID NO:13 in claim 10 (a)
SEQ ID NO:15 in claim 10 (b)
SEQ ID NO:13 and SEQ ID NO:15 in claim 10 (c)
SEQ ID NO:7 in claim 12
SEQ ID NO:7 in claim 19 (a) and (b)
in the reply filed on 11/04/2025 is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 27, 31, 32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.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 1-3, 5-7, 10, 12, 14, 15, 17-19 and 24-26 are under examination on the merits.
Priority
Applicant’s claim for domestic benefit of prior-filed provisional application No. 63/050,275 filed on 07/10/2020 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 11/04/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings were received on 01/10/203. The drawings are objected to because the labels should read “FIG.” instead of “FIGURE”. Further, Fig. 8 is difficult to read.
Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). 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
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
The instant claims require a synthetic antibody comprising a variable heavy chain region comprising an amino acid sequence of SEQ ID NO: 3 and SEQ ID NO: 12, and a variable light chain region comprising an amino acid sequence of SEQ ID NO: 4 and SEQ ID NO: 14. It is noted that SEQ ID NO: 3 is contained within SEQ ID NO: 12, and SEQ ID NO: 4 is contained within SEQ ID NO: 14. Further, it is noted that SEQ ID NO: 7 comprises both the variable heavy and light chain regions of the claimed antibody and as such SEQ ID NO: 7 contains SEQ ID NO: 3, SEQ ID NO: 12, SEQ ID NO: 4, and SEQ ID NO: 14.
Claim Objections
Claims 1-3, 7, 10, 12, 14, 19 are objected to because of the following informalities:
On claims 1-3, 7, 10, 12, 14, 19 the recitation of “Rotavirus” (capitalized) should read “rotavirus” (lower case). Appropriate correction is required.
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.
Claims 1-3, 5-7, 10, 12, 14, 15, 17-19 and 24-26 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.
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.”
The instant claims require a composition comprising nucleic acid molecules encoding an anti-rotavirus antibody comprising:
a variable heavy chain region comprising an amino acid sequence of SEQ ID NO: 3 and SEQ ID NO: 12
a variable light chain region comprising an amino acid sequence of SEQ ID NO: 4 and SEQ ID NO: 14
a variable heavy chain region comprising an amino acid sequence and a variable light chain region comprising an amino acid sequence of SEQ ID NO: 7
The instant claims alternatively require a composition comprising nucleic acid molecules encoding an anti-rotavirus antibody comprising a variable heavy chain region and a light chain region comprising an amino acid sequences having at least 60% identity to SEQ ID NOs: 3 or SEQ ID NO: 4; or SEQ ID NO: 12 or SEQ ID NO: 14; or SEQ ID NO: 7. As such the instant claims comprise a monoclonal antibody wherein sequence alterations can be made anywhere in the amino acid sequences of a variable heavy chain region and a light chain regions (SEQ ID NO: 3 and SEQ ID NO: 4; SEQ ID NO: 12 and SEQ ID NO: 14 or SEQ ID NO: 7) including in the CRD regions, provided that a monoclonal antibody or an antigen-binding fragment thereof bears at least 60% sequence homology to the sequences indicated, wherein the 40% lack of identity is undefined and encompasses sequences with deletion(s), insertion(s) and/or substitution(s) at any position(s) in the sequences indicated.
With respect to the smallest fragments encoding the variable heavy chain region and light chain regions, i.e., SEQ ID NO: 3 and SEQ ID NO: 4; it is noted that SEQ ID NO: 3 is 125 amino acids long, and SEQ ID NO: 4 is 111 amino acids long. The instant claims encompass anywhere from 1 to 50 and 1 to 44 respectively substitutions, deletions, or additions in any combination along any length of SEQ ID NO: 3 and SEQ ID NO: 4. Thus, an enormous genus (2050 = 1.12 x 1065 ; 2044 = 1.76 x 1057) comprising trillions upon trillions of sequences is encompassed by the tremendously broad scope of the claims with respect to the smallest fragments encoding the variable heavy chain region and a light chain regions i.e., SEQ ID NO: 3 and SEQ ID NO: 4. These numbers increase with longer sequences which allow higher number of alterations. Functionally, however, the instant claims require that such genus of variants exhibit binding to a rotavirus.
However, while the claims are drawn to a genus that comprises innumerable sequences, the Specification fails to provide an adequate number of species that would represent the claimed genus of variants possessing the functional properties as required by the claims. The Specification also fails to describe the required contact residues (specific CDRs) which would lead to the claimed binding affinity to a rotavirus. For example, the sequence set forth in SEQ ID NO: 3 is a VH region (Specification, page 21), however the Specification fails to provide which residues could tolerate a substitution yet still maintain the binding affinities as claimed. It is noted that Figure 6 provides the sequences of instant SEQ ID NO: 3 and SEQ ID NO: 4, however, the required binding affinity regions (CDRs) of the sequences are not explicitly claimed nor indicated.
At best, the Specification contemplates the use of BLAST to identify functional homologs based on sequence homology. However, this is not sufficient to describe members of the claimed genus because such methods access online databases that are continually being updated as sequencing technology improves. As a result, they are not a static source of information. Thus, one of skill in the art would readily appreciate that relying on a non-patent source that is continuously subject to change as a means to identify members of the claimed genus does not sufficiently meet the written description requirement.
It is known in the art that even the most minor differences can have significant effects on antigen-antibody binding ability. The art relating to antibodies recognizes that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. 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 that is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain 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 and light chain variable regions is required in order to form functional antigen binding sites. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. ("Single amino acid substitution altering antigen-binding specificity," Proc Natl Acad Sci USA 79:1979-1983 (1982)(See 892-Notice of References Cited). Rudikoff et al. teaches that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function.
Further, Goel et al. (“Plasticity within the Antigen-Combining Site May Manifest as Molecular Mimicry in the Humoral Immune Response,” J. Immunol. 173: 7358-7367 (2004))(See PTO-892: Notice of References Cited) teaches antibodies that bind to the same 12-mer but have very different CDRs; Lloyd et al. (“Modelling the human immune response: performance of a 1011 human antibody repertoire against a broad panel of therapeutically relevant antigens,” Protein Engineering, Design & Selection, Vol. 22, No. 3: 159-168 (2009))(See PTO-892: Notice of References Cited) teaches: on average, about 120 different antibodies in a library can bind to a given antigen; Edwards et al. (“The Remarkable Flexibility of The Human Antibody Repertoire; Isolation of Over One Thousand Different Antibodies to a Single Protein, BLys,” J. Mol. Biol. 334: 103-118 (2003))(See PTO-892: Notice of References Cited) teaches: a library contained over 1000 antibodies that bound to a single 51kDA protein, including unique VH and 705 VL sequences; there were 568 different CDR3 regions. Given the highly diverse nature of antibodies, particularly in the CDRs, one of ordinary skill in the art generally cannot envision the structure of an antibody by knowing its binding characteristics (for example as instantly claimed, anti-rotavirus activity).
Therefore, in light of the knowledge in the art, the broad scope of the claims, and the teachings in the Specification, it is asserted that there is still a high level of uncertainty as to which antibodies fall within the scope of the indicated genus while retaining the ability to bind a rotavirus.
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 rotavirus. However, as discussed above, the Specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to binding to a rotavirus.
Thus, in view of the reasons set forth above, 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 § 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.
Claims 1, 2, 26 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by US 2018/0155411 A1 to Nair et al. Published 06/07/2018 (see PTO-892: Notice of References Cited).
See claims 1, 2, 26 as submitted on 09/21/2023.
Regarding claims 1, 2 and 26, Nair et al. disclose a composition comprising nucleic acid sequences encoding synthetic antibodies against a rotavirus, wherein the composition comprises a nucleotide sequence encoding a variable heavy chain region of an anti-rotavirus antibody, and a nucleotide sequence encoding a variable light chain region of an anti-rotavirus antibody. (Abstract, ¶¶ [0009], [0014]). Nair et al. disclose the composition further comprises a pharmaceutical acceptable excipient (¶ [0155]).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Nair et al. (previously cited), as applied to claims 1, 2, 26 above, in view of Corthésy,et al. “Rotavirus anti-VP6 secretory immunoglobulin A contributes to protection via intracellular neutralization but not via immune exclusion.” Journal of virology vol. 80,21 (2006): 10692-9. (cited in Applicant’s IDS submitted on 11/04/2025) and PGPub US 20100122358 A1 to Bruggemann et al. published on 05/13/2010 (See PTO-892: Notice of References Cited).
See claims 5, 6 as submitted on 09/21/2023.
Regarding claims 5 and 6, Nair et al. disclose the composition of claim 1. Nair et al. do not disclose a J chain comprising an animo acid sequence having at least 60% identity to SEQ ID NO: 16.
However, Corthesy et al. teach a rotavirus anti-VP6 antibody comprising a J chain for retention of polymeric form and proper assembly (pages 2-3, Fig. 1).
Bruggemann et al. are cited for teaching an amino acid sequence for a J chain, the amino acid sequence of Bruggemann et al. shares 100% identity with instant SEQ ID NO: 16. See alignment below (Qy is instant SEQ ID NO: 16; Db is Bruggemann et al.’s SEQ ID NO: 94.)
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It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have incorporated the J chain as taught by Corthesy et al. and Bruggemann et al. into the composition of Nair et al. for the benefit of precenting ensuring retention of polymeric form and proper assembly of an anti-rotavirus antibody. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
One of ordinary skill in the art would have had reasonable expectation of success in incorporating he J chain as taught by Corthesy et al. and Bruggemann et al. into the composition of Nair et al. given that the methods of antibody expression and assembly are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Accordingly, claims 5 and 6 were prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARLENE V BUCKMASTER whose telephone number is (703)756-5371. The examiner can normally be reached M-F 8-5.
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/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672