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 .
Response to Amendment
The Amendment filed 05/11/2026 in which claims 1, 5-7, 10, 12, 14, 15, 17, 19 were amended, new claim 32 was added, and claims 2, 3 were canceled, has been entered. Claims 27, 31, 32 were previously withdrawn. Claims 4, 8-9, 11, 13, 16, 20-23, 28-30, were previously canceled.
Claims 1, 5-7, 10, 12, 14, 15, 17-19 and 24-26 are under examination on the merits.
Drawings
(Previous objection, withdrawn) Applicant’s amendments to the Drawings submitted on 05/11/2026 have overcome the previous objection to the Drawings.
Claim Objections
(Previous objections, withdrawn as to claims 1-3, 7, 10, 12, 14, 19). Applicant’s cancelation of claims 2, 3 are moot in view of Applicant’s cancelation of those claims. Applicant’s amendments to claims 1, 7, 10, 12, 14, 19 have overcome previous objections to claims 1, 7, 10, 12, 14, 19.
(New objection, necessitated by amendment as to claim 1). The recitation of claim 1 part (b) of “encoding a fragment of an anti-rotavirus synthetic antibody” should recite “encoding an antigen binding fragment of an anti-rotavirus synthetic antibody.”
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.
(Previous rejections, withdrawn as to claims 2, 3; maintained and modified as to claims 1, 5-7, 10, 12, 14, 15, 17-19 and 24-26) Claims 1, 5-7, 10, 12, 14, 15, 17-19 and 24-26 are rejected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.
See claims 1, 5-7, 10, 12, 14, 15, 17-19 and 24-26 as submitted on 05/11/2026.
The previous rejections of claims 2, 3 are moot in view of Applicant’s cancelation of these claims.
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: 3 and SEQ ID NO: 4
The amended 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 90% 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 (see Claim Interpretation set forth in the Non-Final Office Action mailed on 02/11/2026), and having binding affinity for a rotavirus. 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 region (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 90% sequence homology to the sequences indicated, wherein the 10% 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. The instant claims alternatively require a composition comprising nucleic acid molecules encoding a fragment of the ani-rotavirus antibody as described above.
With respect to the smallest sequences encoding the variable heavy chain region and a 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 12 and 1 to 11 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 (2012 = 4.1 x 1015 ; 2011 = 2.05 x 1014) comprising trillions upon trillions of sequences is encompassed by the tremendously broad scope of the claims with respect to the smallest sequences 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.
(Previous rejections, withdrawn as to claims 1, 2, 26) Claims 1, 2, 26 were rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by US Nair et al. (Prior art of record).
See claims 1, 2, 26 as submitted on 05/11/2026.
The previous rejection of claim 2 is moot in view of Applicant’s cancelation of claim 2.
Applicant’s amendment to the instant claims filed on 05/11/2026 has overcome the previous rejections to claims 1, 26.
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.
(Previous rejections, withdrawn as to claims 5 and 6) Claims 5 and 6 were rejected under 35 U.S.C. 103 as being unpatentable over Nair et al. (previously cited), in view of Corthésy,et al. and Bruggemann et al. published on 05/13/2010 (Prior art of record).
See claims 5 and 6 as submitted on 05/11/2026.
Applicant’s amendment to the instant claims filed on 05/11/2026 has overcome the previous rejections to claims 5 and 6.
Response to Arguments
Applicant's arguments filed 05/11/2026 have been fully considered but they are not persuasive.
Applicant contends on page 9 of the Remarks submitted on 05/11/2026:
“Applicant submits that a skilled artisan would readily recognize that the Specification sufficiently describes an anti-rotavirus synthetic antibody or fragment thereof as an antibody or fragment thereof having 90% identity to the recited sequences. Applicant submits that 90% identity to the recited sequences encompasses a reasonable number of sequences within its scope. The molecules, including those having 90% identity to the recited sequences, are fully described by the disclosure. One of ordinary skill in the art would recognize that these variants can easily be tested for immunological activity using methods and assays disclosed in the specification, and such experimentation would not be undue. Given the state of the art of antibody development, this experimentation would be necessary as part of ensuring immunogenicity and tolerance by a model organism. Therefore, while some experimentation may be necessary to practice the claimed invention across its full scope, this experimentation would not be undue.”
In response:
The instant rejection is in view of the instant claims merely reciting or reading on a composition comprising nucleic acid molecules encoding an anti-rotavirus antibody or fragment thereof as described above. Although the claims are interpreted in light of the Specification, limitations from the Specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). As indicated above, the amended claims are drawn to a genus that comprises innumerable antibody sequences, the amended claims are also drawn to fragments of those sequences. Most notably, the instant claims fail to describe the required contact residues (specific CDRs) which would lead to the claimed binding affinity to a rotavirus. The CDRs of the claimed antibody are not explicitly claimed nor indicated. Given the broad scope of the claims, and the teachings in the Specification, and the absence of the CDR sequences it is maintained 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. 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.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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-R 8:00 AM - 5:00 PM.
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/MARLENE V BUCKMASTER/
Examiner, Art Unit 1672
/NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672
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