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 without traverse of Group I, claims 1-17 drawn to an antibody or antigen-binding fragment thereof, in the reply filed on 12/29/2025 is acknowledged.
Additionally, Applicant’s election of the following species, in the reply filed on 12/29/2025 is acknowledged:
in claim 1, X1 is G, X3 is T,X5 is T, X6 is G, X7 is Y, X11 is I, X13 is P, X14 is N, X15 is S, X16 is G, X17 is G, X18 is T, X21 is L, X23 is N, X24 is D, X25 is D, X26 is V, X28 is Y, X33 is V, X34 is Q, X35 is S, X36 is I, X38 is T, X39 is Y, X40 is A, X41 is A, X42 is S, X51 is T;
consistent with the election in claim 1, in claim 2,
HCDR1 as shown by SEQ ID NO: 17,
HCDR2 as shown by SEQ ID NO: 21,
HCDR3 as shown by SEQ ID NO: 23,
LCDR1 as shown by SEQ ID NO: 25,
LCDR2 as shown by SEQ ID NO: 28, and
LCDR3 as shown by SEQ ID NO: 32;
in claim 4, Z1 is Q, Z2 is V, Z3 is Q, Z4 is V, Z5 is E, Z6 is V, Z7 is M, Z8 is L, Z9 is M, Z10 is R, Z11 is T, Z12 is I, Z13 is R, Z14 is D, Z15 is K, Z16 is L, Z17 is D, Z18 is I, Z19 is Q, Z20 is S, Z21 is S, Z22 is A, Z23 is V, Z24 is D, Z25 is V, Z26 is I, Z27 is T, Z28 is N, Z29 is K, Z30 is K, Z31 is Y, Z32 is S, Z33 is L, Z34 is Q, Z35 is S, Z36 is V, Z37 is S, Z38 is D, Z39 is S, Z40 is Q, Z41 is P, Z42 is E, Z43 is F, Z44 is G, Z45 is K, Z46 is V, Z47 is D;
consistent with the elections in claims above, in claim 5, VH as shown by SEQ ID
NO: 1;
consistent with the elections in claims above, in claim 6, VL as shown by SEQ ID
NO: 7;
consistent with the elections in claims above, in claim 7, a VH and a VL as shown
by SEQ ID NO: 1 and SEQ ID NO: 7
Claims 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.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 1-17 are under examination on the merits.
Priority
Applicant’s claim for foreign priority of prior-filed Chinese applications No. 202010659026.2 filed on 07/09/2020 and 202010659828.3 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. Receipt is acknowledged of certified copies of documents required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 04/25/2023, 05/22/2024, 07/24/2025. 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 01/04/2021. The drawings are objected to because the labels should read “FIG.” instead of “FIGURE”.
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.
Specification
The use of the term “Tween” for example on page 49, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Note that “Tween” is merely an example and all improper uses of trademarks in the specification should be identified by Applicant and properly addressed.
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 1-17 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 an isolated antibody or antigen-binding fragment thereof comprising HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 amino acid sequences identical to SEQ ID NOs: 17, 21, 23, 25, 28, and 32, respectively. It is noted that claim 1 recites numerous other species comprising amino acid substitutions within each CDR sequence and claims 5-7 further require an antibody or antigen-binding fragment thereof with the VH and VL sequences of SEQ ID NOs: 1 and 7, respectively or any amino acid sequences sharing at least 85% to SEQ ID NOs: 1 and 7. As such the instant claims comprise an isolated antibody or antigen-binding fragment thereof wherein sequence alterations can be made anywhere in the CDRs or anywhere in the amino acid sequences encoding the VH and VL, provided that the VH and VL amino acid sequences bears at least 85% sequence homology to SEQ ID NOs: 1 and 7, respectively, wherein the 15% lack of identity is undefined and encompasses sequences with deletion(s), insertion(s) and/or substitution(s) at any position(s) in the VH and VL sequences indicated.
With respect to the amino acid sequences encoding the VH and VL regions, namely SEQ ID NOs: 1 and 7, it is noted that they are 123 and 108 amino acids long, respectively. The instant claims encompass anywhere from 1 to 18 and 1 to 16 respectively, substitutions, deletions, or additions in any combination along any length of SEQ ID NO: 1 and SEQ ID NO: 7. Thus, an enormous genus (2018 = 2.6 x 1023 ; 2016 = 6.55 x 1020) comprising trillions upon trillions of sequences is encompassed by the tremendously broad scope of the claims. Functionally, however, the instant claims require that such genus of variants exhibit binding to a hepatitis B virus surface antigen (HBsAg).
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 mentions ten antibody sequences which are referred to as 005, 062, 079, 083, 088, 090, 091, 093, 095, and 096 (page 45-47, Table 8). However the Specification fails to provide which residues could tolerate a substitution yet still maintain the binding affinities as claimed.
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; see 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). 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. Further, as Rudikoff et al. teach, alterations of a single amino acid in the CDR regions of a phosphocholine-binding myeloma antibody or antigen-binding fragment thereof 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, specific binding to a hepatitis B virus surface antigen (HBsAg).
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 hepatitis B virus surface antigen (HBsAg).
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 hepatitis B virus surface antigen (HBsAg). 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 hepatitis B virus surface antigen (HBsAg).
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
The following SEQ ID NOs are free of the art: SEQ ID NO: 1 and SEQ ID NO: 7. The elected HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 amino acid sequences according in claim 1 (SEQ ID NOs: 17, 21, 23, 25, 28, and 32, respectively), are not free of the art but are non-obvious as a combination, as shown in SEQ ID NOs: 1 and 7.
Claim 1 would be allowable as to the elected species if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(a), set forth in this Office action.
Claims 2-17 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(a), set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
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-R 8:00 AM - 5:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas J. Visone can be reached on (571)270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
/NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672
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