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 .
Preliminary Amendment
The preliminary amendment dated 02/17/2026 has been entered. Claims 1-8 and 15 are pending and under examination.
Information Disclosure Statement
The submitted Information Disclosure Statement(s) (IDS) dated 04/21/2023 has been considered by the examiner.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The earliest possible effective filing date for the instant claims is October 23, 2020 based on the filing date of the provisional application 63/105,190
Election/Restriction
Applicant’s election without traverse of Group I in the reply filed on 02/17/2026 is acknowledged.
Claims 9-14 and 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 and 15 are under examination.
Applicant’s species election: An antibody or antigen-binding fragment thereof comprising a CDR1H comprising SEQ ID NO: 206, a CDR2H comprising SEQ ID NO: 235, a CDR3H comprising SEQ ID NO: 264, a CDR1L comprising SEQ ID NO: 380, a CDR2L comprising the sequence GAS, a CDR3L comprising SEQ ID NO: 409, a variable heavy chain region comprising SEQ ID NO: 61, and a variable light chain region comprising SEQ ID NO: 90.
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)).
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.
2. Claims 1-5, 7-8 and 15 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
Claim 1 recites the limitation "An isolated antibody or antigen-binding fragment thereof that binds to SARS-CoV-2 spike protein….”. This limitation is unclear because “antibody” is defined to include monoclonal (mAb) and polyclonal antibodies (pAb) or no definition exists for the term. Therefore, the claim encompasses polyclonal antibodies with the six CDRs. However, polyclonal antibodies have many and different antibody species. The CDRs or variable regions could be found on one molecule in the pAb or two. Recitation’s clarity is improved by the following changes: adding “monoclonal” to the limitation. So, the recitation reads: “An isolated monoclonal antibody or antigen-binding fragment thereof that binds to SARS-CoV-2 spike protein…….”.
Appropriate correction is required. See Ex parte Miyazaki, 89 USPQ2d 1207 (BPAI 2008) ("[R]ather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. §112, second paragraph, as indefinite.").
Claim Rejections - 35 USC § 112
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.
3. Claims 1-8 and 15 are 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 a mAb and antigen-binding fragment thereof, each comprising both a VH and VL regions consisting of all 6 CDRs: HCDR1-3 and LCDR1-3, does not reasonably provide enablement for similar antibodies or antigen-binding fragments thereof comprising fewer than six CDRs per molecule. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The breadth of the claims is found in claim 1 drawn to SARS-CoV-2 spike monoclonal or polyclonal antibodies defined by as few as 3 CDRs which represent an enormous genus.
The nature of the invention is a SARS-CoV-2 spike antibody.
The level of skill of one skilled in this art is high.
The breadth of claim 1 includes millions of antibodies or antigen binding fragments thereof species because the recitation “An isolated antibody or antigen-binding fragment thereof that binds to SARS-CoV-2 spike protein, wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain region comprising a CDR1H, a CDR2H, and a CDR3H, and a variable light chain region comprising a CDR1L, a CDR2L, and a CDR3L….” can be interpreted as either a mAb OR a pAb OR the antigen-binding fragment needs to have both the VH and VL regions with all the 6 CDRs and the other claimed protein molecules do not have to and therefore, it could just be, for example, the VH only and, in that were the case, not all 6 CDRs This breadth far overreaches the disclosed functional antibodies of the specification Thus, the breadth of the claims is very different than Applicant’s contribution.
The state of the prior art is such that it is well established in the art that the formation of an intact antigen-binding site of antibodies generally requires the association of the complete heavy and light chain variable regions of a given antibody, 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. 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 (Paul, page 293, first column, lines 3-8 and line 31 to column 2, line 9 and lines 27-30).
Thus, the state of the art recognized that it would be highly unpredictable that a specific antibody comprising less than all six parental CDRs would have antigen binding function. The minimal structure which the skilled artisan would consider predictive of the function of binding the antigen of a murine, human, or humanized antibody includes six CDRs (three from the heavy chain variable region and three from the light chain variable region) in the context of framework sequences which maintain their correct spatial orientation and have the requisite binding function. One of skill in the art would neither expect nor predict the appropriate functioning of the antibody fragments and mutated antibodies of the instant claims as broadly as claimed. Such are encompassed two ways. First, the polyclonal antibody embodiment need not use all six CDRs on one molecule but can split the VH and VL into two molecules.
The fact that the breadth of the claims is not commensurate in scope with the teachings of the specification, paired with the unpredictability known in this art, these claims must be rejected for lacking enablement to their full scope. Undue experimentation is required to screen CDRs not known to function (unknown) to find a framework (unknown) and functional whole antibody (unknown). One must begin with a known such as six parental CDRs.
Moreover, claims not containing elements critical or essential to the practice of the invention, such as antibodies or antibody fragments not having all of the relevant functional complementarity determining regions (CDRs) in the proper site on an appropriate antibody heavy or light chain framework, are not enabled by the disclosure. See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
Note that an enabling disclosure for the preparation and use of only a few analogs of a product does not enable all possible analogs where the characteristics of the analogs are unpredictable. See Amgen Inc. v. Chugai Pharmaceutical Co. Ltd. (18 USPQ 2d 1027 (CAFC 1991)).
In view of the lack of the predictability of the art to which the invention pertains as evidenced by the art above, the lack of guidance and direction provided by Applicant, and the absence of working examples, undue experimentation would be required to make and use functional antibodies comprising fewer than all six parental CDRs or comprising mutated versions thereof, with a reasonable expectation of success, absent a specific and detailed description in Applicant’s specification of how to effectively practice this and absent working examples providing evidence which is reasonably predictive that the claimed antibodies are functional, commensurate in scope with the claimed invention.
Claim Rejections – Improper Markush Grouping
4. Claims 1-8 and 15 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). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of claims 1-8 and 15 are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use that flows from the substantial structural feature for the following reasons::
As disclosed in the sequence comparison below, there seems to be several subgroups of antibodies binding to the SARS-CoV-2 spike protein within the claims. The antibodies in the same subgroup have the same CDRs but between the different subgroups, the antibodies have different CDRs with clearly distinct amino acid sequence similarity and, therefore, different epitopes.
Consequently, the claims recite discrete antibody binding domains do not all share significant structural similarity. 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 (Proc Natl Acad Sci USA 1982 Vol 79 page 1979). Rudikoff teaches that the alteration of a single amino acid in a single CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function (entire article).
The following Table shows the different subgroups based on the CDR regions of claim 1 (specification table 6, pages 187) which share no significant structural similarity between different subgroups.
PNG
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160
1019
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Greyscale
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media_image2.png
658
959
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Greyscale
Although only the HCDRs are used as an example, an artisan would understand that the sequence differences in the CDRs overall (heavy and light) would amount to structural differences in the antibody binding region as a whole, and therefore there would be no structural similarity between the antibodies leading to be functionally equivalent and to their common use.
Lastly, while the claims recite “ an isolated antibody that binds to SARS-CoV-2 spike protein” this is not an art-recognized class of molecules as defined in MPEP 2117 as: that it was known within the art that each member could be substituted one for the other, with the expectation that the same intended result (be functionally equivalent) would be achieved. This antibodies will not to bind the exact same epitopes with the exact same binding properties. As disclosed in the specification, “…provided herein are antibodies that bind to the same or an overlapping epitope of an antibody described herein, e.g., antibodies that compete for binding to SARS-CoV-2 spike protein with an antibody described herein, or antibodies which bind to an epitope which overlaps with an epitope to which an antibody described herein binds.“. It is unclear the extend of the overlap but any overlap can severely affect the function of the antibody. Therefore, in the instant case, the structurally different antibodies are not art-recognized substitutions for each other.
Dependent claims are rejected for failing to resolve the improper Markush grouping.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Conclusion
No claims are allowed.
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/IMMA BARRERA/
Examiner, Art Unit 1671
/Michael Allen/ Supervisory Patent Examiner, Art Unit 1671