8DETAILED 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 .
Applicant’s amendment, filed on 5/24/2023, is acknowledged.
Claims 1, 4-7, 10-21, 24, 25, 28-39, 42, 43, 45-50, 52, 53, 56, 57, 61-64, 67, 70-73, 76, 77, 79-81, 83-87, and 89-94 are cancelled.
Claims 2, 3, 8, 9, 22, 23, 26, 27, 40, 41, 44, 51, 54, 55, 58-60, 65, 66, 68, 69, 74, 75, 78, 82, and 88 are currently pending.
Claim 2 is the only independent claim.
Election/Restrictions
Applicants’ election with traverse of Group I, claims 2, 3, 8, 9, 22, 23, 26, 27, 40, 41, 44, 51, 54, 55, 58-60, 65, 66, 68, 69, 74, 75, and 82 directed to an anti-TIGIT moiety, and the Species of: 1) an anti-TIGIT moiety comprising HCDR1-3 of SEQ ID NO: 3, 4, and 5 and a LCDR1-3 of SEQ ID NO: 6, 7, and 8, the VH of SEQ ID NO: 110 and VL of SEQ ID NO: 111, and scFv sequence of SEQ ID NO: 99; 2) a first polypeptide comprising SEQ ID NO: 87; and 3) a second polypeptide chain comprising SEQ ID NO: 88 filed on 1/27/2026, is acknowledged.
The traversal is on the grounds that the search and examination would not pose and undue burden on the Examiner. This is not found persuasive because the Inventive Groups lack Unity of Invention and would pose a search burden on the Examiner for the reasons discussed in the Restriction Requirement mailed on 12/11/2025.
The requirement is still deemed proper and is therefore made FINAL.
Claims 75, 78 and 88 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions or species.
Claims 2, 3, 8, 9, 22, 23, 26, 27, 40, 41, 44, 51, 54, 55, 58-60, 65, 66, 68, 69, 74, and 82 are under examination as reading on an anti-TIGIT moiety comprising a HCDR1-3 of SEQ ID NO: 3, 4, and 5, respectively, and a LCDR1-3 of SEQ ID NO: 6, 7, and 8, respectively.
Priority
Applicant’s claim for the benefit of a prior-filed China Patent Application 202011353447.9, filed November 26, 2020, is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 5/24/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner in its entirety.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code disclosed in the instant Specification in ¶[00046]. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 2, 3, 8, 9, 22, 23, 26, 27, 40, 41, 44, 51, 54, 55, 58-60, 65, 66, 68, 69, 74, and 82 are objected to for the following:
Claim 2 recites the acronym “TIGIT”. This is not a readily recognized acronym in the art, such as “DNA” for 5’-deoxyribonucleic acid. Please define the acronym “TIGIT” when these are first used in the claims. Dependent claims 3, 8, 9, 22, 23, 26, 27, 40, 41, 44, 51, 54, 55, 58-60, 65, 66, 68, 69, 74, 78, 82, and 88 do not resolve this issue and are also objected to.
Claim 54 is additionally objected to because the claim currently recites “…an heavy-chain variable region…” and should most likely recite “…a heavy-chain variable region…” to resolve a minor typographical error.
Additionally, claim 65 currently recites “…according to any one of claims 60-64 claim 60…” and should most likely recite “…according to claim 60…” to resolve a typographical error.
Appropriate correction is required.
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.
Claims 2, 3, 8, 9, 22, 23, 26, 27, 40, 41, 44, 51, 54, 55, 58-60, 65, 66, 68, 69, 74, and 82 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 claims 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 inventors, at the time the application was filed, had possession of the claimed invention.
Claims 2, 3, 8, 9, 22, 23, 26, 27, 40, 41, 51, 54, 55, 58, 65, 66, 68, 69, and 74 recite open language “comprising” and “an amino acid sequence as set forth in” one of the recited amino acid sequences. For example, claim 2 recites “…said VH comprises an amino acid sequence as set forth in SEQ ID NO: 55”.
These phrases result in an antibody comprising the claimed antibody or any portion of the claimed amino acid sequences. The claim terminology “an amino acid sequence of” an amino acid sequence does not place size limits on the VH/VL/CDRs, but rather reads on any portion of the claimed VH/ VL/ CDRs of SEQ ID NO. The VH/VL/CDRs are generic with respect to size, encompassing anything from dimers on up to the full size of the claimed SEQ ID NOs. Dependent claims 44, 59, 60, 68, 69, and 82 do not resolve the issues of the claims in which they depend on and are also rejected under 35 U.S.C. § 112(a) Written Description.
Claims 2, 3, 8, 9, 22, 23, 26, 27, 40, 41, 44, 51, 54, 55, 58-60, 68, 69, 74, and 82 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 the structures of the anti-TIGIT antibodies comprising all 6 CDRs or the VH/VL amino acid sequences of the antibodies 900324, 900423, 900424, 900428, HB0030, HB0031, HB0032, and HB0033, does not reasonably provide enablement for the broad genera of antibodies with a partial structure at best and the function of “specifically binding to a TIGIT protein”. 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 and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
Breadth of claims and nature of invention:
Claims 2, 3, 8, 9, 22, 23, 26, 27, 40, 41, 44, 51, 54, 55, 58-60, 68, 69, 74, and 82 encompass broad genera of anti-TIGIT antibodies with a partial structure at best and the recited function of “specifically binding to a TIGIT protein”. For example, instant claim 2 encompasses a genus of anti-TIGIT antibodies comprising at least one CDR in the VH sequence of SEQ ID NO: 55, which includes CDRs with undefined amino acid residues, and an undefined VL with the recited function of “specifically binding to a TIGIT protein”. Claim 23 encompasses a broad genus of antibodies with a defined VH sequence, but with an undefined VL sequences, and the recited function of “specifically binding to a TIGIT protein”, and claim 41 encompasses a broad genus of antibodies with a defined VL sequence, but with an undefined VH sequences, and the recited function of “specifically binding to a TIGIT protein”. As they are currently written, the claims encompass broad genera of millions to billions of different antibody structures, defined by their amino acid sequences especially in the 6 CDR regions critical for binding, with the recited function of “specifically binding to a TIGIT protein”.
The specification discloses the identification of antibodies that specifically bind to TIGIT that were identified from screening antibodies produced from hybridomas that were raised against TIGIT, followed by humanization (Examples 1 and 2).
Amount of direction and existence of working examples:
Multiple antibody clones were identified that were able to specifically bind to TIGIT (¶[000252]): “[t]esting of the binding activity of chimeric antibodies 900324, 900423, 900424, and 900428, humanized antibodies HB0030, HB003 l, HB0032, and HB0033, and cells (CHOKl-huTIGIT-2A3, Huabo Biopharm) expressing the human TIGIT…”. Tables 8 and 9 disclose these anti-TIGIT antibodies being incorporated into bispecific antibodies that also bind to PD-L1.
Each of these clones were identified from a large screen of clones to identify individual antibody structures with the function of “specifically binding to a TIGIT protein”. No guidance on the relationship between an antibody’s structure and the function of “specifically binding to a TIGIT protein” was provided that would allow one with ordinary skill in the art be able to identify additional structures with this function without going through the same or a similar screening process as was disclosed in the instant Specification.
Level of predictability, state of prior art, and quantity of experimentation needed:
The claims are directed to genera of antibodies with a partial structure at best and the recited function of “specifically binds to a TIGIT protein”, which include millions to billions of different antibody structures with varying CDR sequences with the recited function.
However, the specification did not give the skilled in the art enough information to choose candidate antigen binding structures from the vast number of options of millions of candidates, and therefore required scientists to engage in a great deal of experimentation and failure. “That is not enablement”—it is a “hunting license.”
The specification discloses eight examples of different defined antibody clones with the function of “specifically binds to a TIGIT protein”. These antibody clones, defined by their specific amino acid sequences, have a great deal of variation between their CDR regions. For example, the HCDR sequences of clones 900423 and 900424 were both found to bind TIGIT, however these clones have at least 10 different amino acid residues in the CDR regions (compare, for example, SEQ ID NO: 1 and SEQ ID NO: 32)3). The instant specification does not disclose any guidance on which amino acid sequence structures would predictably give rise to antibodies with the function of “specifically binds to a TIGIT protein”.
In Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Supreme Court held that claims drawn to a genus of monoclonal antibodies, which were functionally claimed by their ability to bind to a specific protein, PCSK9, were invalid due to lack of enablement. The claims at issue were functional, in that they defined the genus by its function (the ability to bind to specific residues of PCSK9) as opposed to reciting a specific structure (the amino acid sequence of the antibodies in the genus). The Supreme Court concluded that the patents at issue failed to adequately enable the full scope of the genus of antibodies that performed the function of binding to specific amino acid residues on PCSK9 and blocking the binding of PCSK9 to a particular cholesterol receptor, LDLR. This decision reaffirmed the prior decision made by the Federal District Court in Amgen Inc. v. Sanofi, Aventisub LLC., 987 F.3d 1080 (Fed. Cir. 2021).
The Court clarified that the specification does not always need to "describe with particularity how to make and use every single embodiment within a claimed class." Id. at 610-11. However, "[i]f a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class….The more one claims, the more one must enable." Id.
The specification may require a reasonable amount of experimentation to make and use the invention and what is reasonable will depend on the nature of the invention and the underlying art. For example, "it may suffice to give an example (or a few examples) if the specification also discloses some general quality … running through the class that gives it a peculiar fitness for the particular purpose" and "disclosing that general quality may reliably enable a person skilled in the art to make and use all of what is claimed, not merely a subset." Id. at 611 (internal quotations omitted). However, the Supreme Court found that Amgen failed to enable all that it claimed, even if allowing for a reasonable degree of experimentation. Id. at 613; see also Baxalta Inc. v Genentech, Inc., 81 F.4th 1362, 1367, 2023 USPQ2d 1103 (Fed. Cir. 2023) ("[t]he facts of this case are more analogous to—and are, in fact, indistinguishable from—those in Amgen. We do not interpret Amgen to have disturbed our prior enablement case law, including Wands and its factors."). Moreover, "[w]e see no meaningful difference between Wands' ‘undue experimentation’ and Amgen's ‘[un]reasonable experimentation’ standards. Id. at footnote 4. See also Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024), which explains that regardless of the technology the Wands factors should be used when assessing enablement.
However, while the specification in Amgen identified 26 exemplary antibodies that performed the claimed function by their amino acid sequences, the claims at issue were directed to a class which included "a ‘vast’ number of additional antibodies" that Amgen had not described by their amino acid sequences. Id. at 613. The Court found that Amgen sought to monopolize an entire class by their function, even though that class was much broader than the 26 exemplary antibodies disclosed by their amino acid structure. Id. at 613.
In Amgen Inc. v. Sanofi, Aventisub LLC, 987 F.3d 1080 (Fed. Cir. 2021), which the Supreme Court affirmed, the Federal Circuit explicitly applied the Wands factors to assess whether the specification of Amgen’s patent provided sufficient enablement, for purposes of 35 U.S.C. 112(a), to make and use the full scope of the claimed invention. The court relied on evidence showing that the scope of the claims encompassed millions of antibodies and that it was necessary to screen each candidate antibody in order to determine whether it met the functional limitations of the claim. Id. at 1088. Consequently, the Federal Circuit concluded that there was a lack of enablement. See also the following cases across various technology areas: McRO, Inc. v. Bandai Namco Games Am. Inc., 959 F.3d 1091, 2020 USPQ2d 10550 (Fed. Cir. 2020); Wyeth & Cordis Corp. v. Abbott Laboratories, 720 F.3d 1380, 107 USPQ2d 1273 (Fed. Cir. 2013); Enzo Life Sciences, Inc. v. Roche Molecular Systems, Inc., 928 F.3d 1340 (Fed. Cir. 2019); and Idenix Pharmaceuticals LLC v. Gilead Sciences Inc., 941 F.3d 1149, 2019 USPQ2d 415844 (Fed. Cir. 2019).
Amgen attempted to claim an entire class of compounds by their function, namely antibodies that bind to the “sweet spot” of PCSK9 thereby inhibiting it from binding to LDL, while only describing 26 amino acid sequences in its specification. The two processes, the “roadmap” and “conservative substitution” did not save Amgen. According to the Court, these amounted to “little more than two research assignments” which forced scientists to conduct “painstaking experimentation” to see what worked. (citing Incandescent Lamp). The Court therefore held that Amgen’s specification did not enable the claims.
This case is akin to the issue in Amgen Inc. v. Sanofi, Aventisub LLC, in which the court relied on evidence showing that the scope of the claims encompassed millions of antibodies and that it was necessary to screen each candidate antibody in order to determine whether it met the functional limitations of the claim. Sanofi-Aventisub at 1088. Consequently, the Federal Circuit concluded that there was a lack of enablement. While the specification in Amgen identified 26 exemplary antibodies that performed the claimed function by their amino acid sequences, the claims at issue were directed to a class that included “a ‘vast' number of additional antibodies” that Amgen had not described by their amino acid sequences. Id. at 1256. The Supreme Court found that Amgen sought to monopolize an entire class of antibodies by their function, which was much broader than the 26 exemplary antibodies disclosed by their amino acid structure.
In the instant case, the claims are directed to broad classes of antibodies with a partial structure at best and the recited function of “specifically binds to a TIGIT protein”, while the instant specification discloses only 8 of antibody structures with this function, and has not provided guidance on which antibody amino acid sequence structures would predictably give rise to antibodies with the function of “specifically binds to a TIGIT protein”.
The instant claims are directed to a class of antibodies that include “a ‘vast’ number” of additional structures (i.e., amino acid sequences of all of the CDR regions that are necessary for antigen) in which the instant specification fails to describe. It would be necessary to first generate and then screen each candidate antibody to determine whether it met the function limitations of “specifically binds to a TIGIT protein”. The Federal Circuit concluded that there was a lack of enablement, which was affirmed by the Supreme Court in Amgen.
The instant specification does not disclose any common structural feature delineating which antibody variants would have the function of “specifically binds to a TIGIT protein”, or how to distinguish between antibody structures with this function from ones without. The only structure-function relationship guidance the specification provides is to disclose individual antibodies with this function.
The instant claims simply direct skilled artisans to engage in the same iterative, trial-and-error process the inventors followed to discover the antibody structures they elected to disclose and that “[u]nder Amgen, such random trial-and-error discovery, without more, constitutes unreasonable experimentation that falls outside the bounds required by § 112(a).” Id. at *8, *10.
Applicant is relying upon certain biological activities such a antibodies that target TIGIT and a limited number of species of antibodies with defined structures (e.g. amino acid sequences) to support an entire genus of diverse and structurally unrelated inhibitory antibody. Yet the instant specification does not provide sufficient guidance and directions as to the structural features of the inhibitory antibody and the correlation between the structure and the desired antigen binding and inhibitory function.
The Supreme Court’s 2023 decision in Amgen v. Sanofi, which mainly involves the enablement requirement, states that “where a patentee purports to invent an entire genus, it must enable the entire genus”; “disclosing how to produce some antibodies that perform a specified function is not equivalent to disclosing how to produce all such antibodies – and it is the latter that petitioners claim as their invention”; S. Ct.
Additionally, in its recent decision in Baxalta Inc. v. Genentech, Inc., No. 2022-1461, 2023 WL 6135930 (Fed. Cir. Sept. 20, 2023) the Federal Circuit found the facts of this case to be "materially indistinguishable from those in Amgen." Baxalta, 2023 WL 6135930, at *4. According to the Federal Circuit, claim 1 covers "millions of potential candidate antibodies" (id.) that bind to Factor IX/IXa and increase the procoagulant activity of Factor IXa. The court, however, noted that the specification discloses the amino acid sequence of just 11 of those antibodies. And like the roadmap in the patents at issue in Amgen, "the '590 patent's roadmap simply directs skilled artisans to engage in the same iterative, trial-and-error process the inventors followed to discover the [11] antibodies they elected to disclose." (Id.) Missing from the specification, according to the Federal Circuit, was "'a quality common to every functional embodiment' ... that would allow a skilled artisan to predict which antibodies will perform the claimed functions" (id.; quoting Amgen Inc. v. Sanofi., 598 U.S. 594, 614 (2023)), such as a common structural or other feature that would allow the antibodies to perform the claimed functions, or an explanation as to why the 11 antibodies do so and others do not. (Baxalta, 2023 WL 6135930, at *4). And the Federal Circuit was not persuaded by Baxalta's argument that its disclosed hybridoma-and screening process "predictably and reliably generates new claimed antibodies every time it is performed" (id.), because "it is undisputed that to practice the full scope of the claimed invention, skilled artisans must make candidate antibodies and screen them to determine which ones perform the claimed functions." (Id.).
The specification does not reasonably provide enablement to make and use the invention of instant claims 2, 3, 8, 9, 22, 23, 26, 27, 40, 41, 44, 51, 54, 55, 58-60, 68, 69, 74, and 82. The specification does enable one with ordinary skill to make the antibody clone discussed supra.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
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.
Claims 2, 3, 8, 9, 22, 23, 26, 27, 40, 41, 44, 51, 54, 55, 58-60, 68, 69, 74, and 82 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.
Claims 2, 3, 8, 9, 22, 23, 26, 27, 40, 41, and 82 are rejected under 35 U.S.C. 112(b) as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The preamble and the body of the claim do not match. The preamble of claim 2 currently recites “a polyspecific antibody”, while the body of claim 2 only recites one antigen targeting moiety. It is currently unclear whether the scope of the claim covers anti-TIGIT binding moieties alone or if the antibody should be at least bispecific and comprise at least a second antigen binding arm. Claims 3, 8, 9, 22, 23, 26, 27, 40, 41, and 82 do not resolve this issue and are also rejected as indefinite. Amending claim 2 to recite the polyspecific antibody further comprising a second antigen binding arm would resolve this issue.
Additionally, claims 2, 3, 8, 22, 26, 27, 40, 41, 44, 51, 54, 55, 58-60, 68, 69, 74, and 82 are indefinite because each of the following claims recite amino acid sequences with undefined residues without a recitation of the possibilities that the residues can be, rendering the claims indefinite. It is currently unclear if each undefined residue in the sequences refers to any amino acid or a more limited set of amino acids:
Claim 2, SEQ ID NO: 55
Claim 3, SEQ ID NO: 64
Claim 8, SEQ ID NO: 56 and 57
Claim 26, SEQ ID NO: 65 and 66
Claim 40, SEQ ID NO: 64
For example, the sequence listing of SEQ ID NO: 56 recited in claim 6 is listed as the following in the Sequence Listing:
I Xaa Xaa S G Xaa Xaa
wherein the first Xaa is Ser or Thr, the second Xaa is Ser or Tyr, the third Xaa is Ala or Ser, and the fourth Xaa is Pro or Thr. It is currently unclear if the claimed Xaa positions are limited to the specific amino acid residues in the Sequence Listing
Dependent claims 22, 27, 41, 44, 51, 54, 55, 58-60, 68, 69, 74, and 82 do not resolve the issue(s) and are also rejected under 35 U.S.C. § 112(b) as indefinite. Amending the claims to recite the possible residue or residues for each specific undefined Xaa position in the claimed sequences with undefined positions would resolve this issue.
Claim 54 is additionally indefinite because the claim currently recites “…wherein said antibody capable of binding to PD-L1 protein comprises an heavy-chain variable region VH, and said VH comprises an amino acid sequence as set forth in SEQ ID NO: 108 or 110.” However, the specification discloses at ¶[000174]: “In the present application, the antibody capable of binding to the PD-LI protein may comprise VH. For example, the VH may comprise an amino acid sequence as set forth in SEQ ID NO: 106 or 108.” It is currently unclear how SEQ ID NO: 110, which is an anti-TIGIT VH region (see species election supra), also is a VH of a binding region that specifically binds to PD-L1.
Claim Rejections - 35 USC § 103
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 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 2, 3, 8, 9, 22, 26, 27, 40, and 82 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (WO2021227940, machine translation attached to end of application).
Yu et al. (WO2021227940) is published on 11/18/2021 with a priority date of 5/19/2020, which is before the effective filing date of 11/26/2020 of the instant application.
Yu et al. teaches anti-TIGIT antibodies including HB0030, which comprises the VH of SEQ ID NO: 9 and the VL of SEQ ID NO: 10. SEQ ID NO: 9 contains the HCDR1-3 sequences of instant SEQ ID NO: 3, 4, and 5 (i.e., the limitations of instant claims 2, 8, 9, and 22):
Qy 1 GYSITSDYA 9 1 ITSSGST 7
||||||||| |||||||
Db 1 QVQLQESGPGLVKPSETLSLTCTVSGYSITSDYAWIWIRQPPGKGLEWIGYITSSGSTYY 60
Qy 1 ARLDFGNYGGAMDY 14
||||||||||||||
Db 61 NPSLKSRVTFSVDTSKNQFSLKLSSVTAADTATYYCARLDFGNYGGAMDYWGQGTLVTVS 120
SEQ ID NO: 10 contains the LCDR1-3 sequences of instant SEQ ID NO: 6, 7, and 8 (i.e., the limitations of instant claims 3, 26, 27, and 40):
Qy 1 QHVSTA 6 1 SAS 3
|||||| |||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQHVSTAVNWYQQKPGKAPKLLIYSASYLYSGVPS 60
Qy 1 QQHYITPYT 9
|||||||||
Db 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYITPYTFGQGTKLEIK 107
Yu et al. additionally teaches that the anti-TIGIT antibody can be in the form of a bispecific or multispecific antibody (pg. 7 and 8 of machine translation): “[i]n this application, the term "antibody" is used in the broadest sense, and specifically covers, but is not limited to, monoclonal antibodies (including full-length monoclonal antibodies comprising two light chains and two heavy chains), polyclonal antibodies , Multispecific antibodies (such as bispecific antibodies)…”
Yu et al. further teaches pharmaceutical compositions comprising the anti-TIGIT antibodies and an acceptable carrier (i.e., the limitations of instant claim 82, pg. 21 of machine translation): “…the composition may be a pharmaceutical composition which contains the antigen binding protein…and a pharmaceutically acceptable carrier.”
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant application, to have incorporated the anti-TIGIT antibodies taught by Yu et al. into polyspecific formats with a reasonable expectation of success, as Yu et al. teaches that the anti-TIGIT antibodies can be in multispecific formats. One would have been motivated to make this change to make bispecific/polyspecific antibodies comprising one anti-TIGIT antigen binding arm, as Yu et al. teaches this as well.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim 44 is rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (supra) as applied to claims 2, 3, 8, 9, 22, 26, 27, 40, and 82 above, and further in view of Ma et al. (Biochem Biophys Res Commun. 2020 Oct 15;531(2):144-151. doi: 10.1016/j.bbrc.2020.07.072. Epub 2020 Aug 8).
The teachings of Yu et al. are discussed supra. Yu et al. does not teach bispecific anti-PD-L1 and anti-TIGIT bispecific antibodies (i.e., the limitations of instant claim 44)
Ma et al., in the same field of endeavor, teaches anti-TIGIT/anti-PD-L1 bispecific antibodies for dual checkpoint inhibition to activate T-cells for cancer treatment (Abstract): “…we demonstrated that the BsAb retained high blocking activity towards PD-1/PD-L1 or TIGIT/CD155 interaction. The BsAb synergistically enhanced T cell activities in vitro compared to two parental Nbs. Taken together, we obtained a multivalent BsAb blocking biological function of PD-L1 and TIGIT and it is worthy to further study the anti-tumor activities of this BsAb in vivo.”
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant application, to have modified the teachings of Yu et al. in view of Ma et al. to have incorporated the anti-TIGIT antibody of Yu et al. into a bispecific antibody that is also targeting PD-L1 with a reasonable expectation of success, as Ma et al. teaches such bispecific antibodies can be made and used to enhance T-cell activation. One would have been motivated to make this change for the purposes of making an anti-TIGIT/anti-PD-L1 bispecific antibody that targets both checkpoint inhibitors to synergistically enhance T-cell activation, as taught by Ma et al.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 23, 41, 59, 68 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (supra) and Ma et al. (supra), as applied to claims 2, 3, 8, 9, 22, 26, 27, 40, 44 and 82 above, and further in view of Koopmans et al. (Oncoimmunology. 2018 May 31;7(8):e1466016. doi: 10.1080/2162402X.2018) and Metz et al. (Protein Eng Des Sel. 2012 Oct;25(10):571-80. doi: 10.1093/protein/gzs064. Epub 2012 Sep 13).
The combined teachings of Yu et al. and Ma et al. are discussed supra. The combined teachings do not teach an anti-PD-L1/anti-TIGIT bispecific antibody comprising VH and VL domains for teach antigen binding moiety wherein the anti-TIGIT VH has the G44C mutation and the VL has the Q100C mutation (i.e., the limitations of instant claims 23 and 41). For example, Ma et al. only teaches anti-PD-L1 nanobodies to be used in bispecifics.
Koopmans et al., in the same field of endeavor, teaches an anti-PD-L1 antibody which is not a nanobody that can be used in bispecific antibodies for the treatment of cancer (“Construction of PD-L1xEGFR” section and Abstract): “[t]o address these issues, we constructed a bispecific antibody (bsAb), designated PD-L1xEGFR…”
Metz et al., in the same field of endeavor, teaches a flexible bispecific antibody format where one antigen binding moiety is a full-length antibody and the other antigen binding moiety is a scFv (Figure 1A):
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319
599
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Figure 1 of Metz et al. teaches that the VH and VL of one antibody is fused to the VH of a second antibody scFv, and the VL of the second antibody scFv is co-expressed with the first polypeptide to form the bispecific antibody (see Fig 1A and B, the dark shaded portion of the scFv is the VH).
Metz et al. teaches that the that a G44C mutation in an antibody VH domain and a Q100C mutation in the VL domain stabilized antibodies by introducing a disulfide bond between the VH and VL region without affecting antibody structure and antigen binding (Introduction): “[a]mong different possibilities to stabilize VH–VL heterodimers by interchain disulfides, the connection between VH,cys44 and VL,cys100 turned out as a versatile position that works for most Fvs without affecting structure and interfering with antigen binding…” Also see Fig. 1B (“44-100”):
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171
431
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Metz et al. teaches that the bispecifics has one antibody binding site that is sterically restricted until cleaved by a protease, making the bispecific antibody activatable (Introduction): “[t]he bispecific antibody format that we describe here enables in mammalian cells the production of antibody derivatives containing dsFvs without any linker. The format was subsequently adapted to generate entities with freely accessible binding activity towards one target and another ‘restricted’ specificity. Compared with bivalent IgG arms, this second binding activity is reduced by monovalency and—most important—in its ‘restricted’ form severely compromised by steric hindrance. Activation by specific proteases releases this restriction and thus renders the second binding entity fully functional.”
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant application, to have modified the combined teachings of Yu et al. and Ma et al. further in view of Koopmans et al. and Metz et al. to develop an anti-PD-L1/anti-TIGIT activatable bispecific antibody wherein the anti-TIGIT antibody is in the form of an scFv with the VH G44C mutation and VL Q100C mutations (i.e., the limitations of instant claims 23 and 41) with a reasonable expectation of success, as Metz et al. teaches methods of making such a bispecific antibody and Koopmans et al. teaches an anti-PD-L1 antibody that can be incorporated into a bispecific with the anti-TIGIT antibody taught by Yu et al. One would have been motivated to make this change for the purposes of generating an activatable anti-TIGIT/anti-PD-L1 bispecific antibody without any linker, as taught by Metz et al. Additionally, Ma et al. teaches that such a bispecific can synergistically activated T-cells to treat cancer.
Introducing a G44C mutation to the anti-TIGIT antibody VH domain taught by Yu et al. (SEQ ID NO: 9) generates a VH domain that is 100% identical with instant SEQ ID NO: 110 (i.e., the limitations of instant claim 23):
Qy 1 QVQLQESGPGLVKPSETLSLTCTVSGYSITSDYAWIWIRQPPGKCLEWIGYITSSGSTYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLQESGPGLVKPSETLSLTCTVSGYSITSDYAWIWIRQPPGKCLEWIGYITSSGSTYY 60
Qy 61 NPSLKSRVTFSVDTSKNQFSLKLSSVTAADTATYYCARLDFGNYGGAMDYWGQGTLVTVS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NPSLKSRVTFSVDTSKNQFSLKLSSVTAADTATYYCARLDFGNYGGAMDYWGQGTLVTVS 120
Qy 121 S 121
|
Db 121 S 121
Introducing a Q100C mutation to the anti-TIGIT antibody VL domain taught by Yu et al. (SEQ ID NO: 10) generates a VL domain that is 100% identical with instant SEQ ID NO: 111 (i.e., the limitations of instant claim 41):
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQHVSTAVNWYQQKPGKAPKLLIYSASYLYSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQHVSTAVNWYQQKPGKAPKLLIYSASYLYSGVPS 60
Qy 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYITPYTFGCGTKLEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYITPYTFGCGTKLEIK 107
Regarding claims 59 and 68, one with ordinary skill in the art would appreciate that either the anti-TIGIT antibody can be in the form of an IgG and an scFv in the bispecific antibody format taught by Metz et al. If the anti-PD-L1 antibody is a scFv and the anti-TIGIT antibody is an IgG, then the anti-PD-L1 scFv VH would be fused to the heavy chain of the anti-TIGIT IgG, and this polypeptide would comprise the anti-TIGIT VH and VL the anti-PD-L1 VH, while the remaining anti-PD-L1 VL is expressed a separate polypeptide, meeting the limitations of instant claim 59. Additionally, if the anti-TIGIT antibody is a scFv and the PD-L1 antibody is an IgG, then the anti-TIGIT scFv VH would be fused to the heavy chain of the PD-L1 IgG, and this polypeptide would comprise the PD-L1 VH and VL the anti-TIGIT VH , while the remaining anti-TIGIT VL is expressed a separate polypeptide, meeting the limitations of instant claim 68. One with ordinary skill in the art would make both formats over the course of routine experimentation. See MPEP § 2144.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 59, 60, 68, and 69 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (supra) and Ma et al. (supra), as applied to claims 2, 3, 8, 9, 22, 26, 27, 40, 44 and 82 above, and further in view of Koopmans et al. (supra) and Coloma et al (Nat Biotechnol. 1997 Feb;15(2):159-63. doi: 10.1038/nbt0297-159).
The combined teachings of Yu et al. and Ma et al. are discussed supra. The combined teachings do not teach an anti-PD-L1/anti-TIGIT bispecific antibody comprising VH and VL domains for teach antigen binding moiety wherein the antibody format is fusion of an scFv version of one of the antibodies to the heavy chain of the second antibody in an IgG format (i.e., the limitations of instant claims (59, 60, 68, and 69).
Koopmans et al., in the same field of endeavor, teaches an anti-PD-L1 antibody which is not a nanobody that can be used in bispecific antibodies for the treatment of cancer (“Construction of PD-L1xEGFR” section and Abstract): “[t]o address these issues, we constructed a bispecific antibody (bsAb), designated PD-L1xEGFR…”
Coloma et al., in the same field of endeavor, teaches design and production of a bispecific antibody with the format of an IgG-scFv fusion, where one antibody is in the format of a full-length IgG, and the second antibody is an scFv fused to the heavy chain of the IgG (Abstract): “[w]e have produced novel bispecific antibodies by fusing the DNA encoding a single chain antibody (ScFv) after the C terminus (CH3-ScFv) or after the hinge (Hinge-ScFv) with an antibody of a different specificity…”
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant application, to have to have modified the combined teachings of Yu et al. and Ma et al. further in view of Koopmans et al. and Coloma et al. to develop an anti-PD-L1/anti-TIGIT IgG-scFv bispecific antibody with a reasonable expectation of success, as Coloma et al. teaches design and production of a bispecific antibody with this format. One would have been motivated to make this change for the purposes of making a functional bispecific antibody that binds to both TIGIT and PD-L1 to synergistically activate T-cells to treat cancer.
Additionally, one with ordinary skill in the art would appreciate that either the anti-TIGIT antibody can be in the form of an IgG and an scFv in the bispecific antibody format taught by Coloma et al. If the anti-TIGIT antibody is a scFv and the PD-L1 antibody is an IgG, then the anti-TIGIT scFv would be fused to the heavy chain of the PD-L1 IgG, and this polypeptide would comprise the PD-L1 VH and the anti-TIGIT VH and VL, while the remaining PD-L1 VL is a separate polypeptide, meeting the limitations of instant claims 59 and 60. If the anti-PD-L1 antibody is a scFv and the TIGIT antibody is an IgG, then the anti-PD-L1 scFv would be fused to the heavy chain of the TIGIT IgG, and this polypeptide would comprise the anti-TIGIT VH and the anti-PD-L1 VH and VL, while the remaining PD-L1 VL is a separate polypeptide, meeting the limitations of instant claims 68 and 69. One with ordinary skill in the art would make both formats over the course of routine experimentation. See MPEP § 2144.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim 65 is rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (supra) and Ma et al. (supra), Koopmans et al. (supra), and Coloma et al. (supra), as applied to claims 2, 3, 8, 9, 22, 26, 27, 40, 44, 59, 60, 68, 69, and 82 above, and further in view of Paudel et al. (J Biotechnol. 2017 Jun 10;251:47-52. doi: 10.1016/j.jbiotec.2017.04.002. Epub 2017 Apr 7) and Huang et al. (J Biol Chem. 2010 Mar 12;285(11):7880-91. doi: 10.1074/jbc.M109.061457).
The combined teachings of Yu et al., Ma et al., Koopmans et al., and Coloma et al. have been discussed supra. Additionally, Yu et al. teaches that the anti-TIGIT antibodies can be in an scFv format (pg. 8 of machine translation): “…the term "scFv" generally refers to a monovalent molecule formed by covalently connecting and pairing a heavy chain variable domain and a light chain variable domain of an antibody through a flexible peptide linker; such scFv molecules may have general Structure: NH2 -VL-linker-VH-COOH or NH2 -VH-linker-VL-COOH”
The combined teachings do not teach a specific scFv linker, such as (GGGGS)5, nor do they teach the VH G44C and VL Q100C mutations in an anti-TIGIT scFv, or a bispecific antibody comprising the anti-TIGIT scFv of SEQ ID NO: 99 (i.e., the limitations of instant claim 65).
Paudel et al., in the same field of endeavor, teaches scFvs with the format VH-(GGGGS)n-VL, where n = 5 (Abstract): “[p]eptide linkers of three different lengths were constructed to join the variable regions of the heavy chain (VH) and the light chain (VL) in a single-chain variable fragment antibody (scFv) specific for wogonin glucuronide (Wgn) that has the structure VH-(GGGGS)n–VL (n= 3, 5, or 7).”
Huang et al., in the same field of endeavor, teaches introducing an interdomain disulfide bond between the VH and VL of an scFv to stabilize the scFv (Abstract): “[t]he stability of the variable domain structures can be enhanced with interdomain disulfide bond…”. Huang et al. teaches that the Q100C mutation in the VL and the G44C mutation in the VH of an scFv to introduce an interchain disulfide bond (Results, pg. 7883): “…S5 (L:Q100C and H:G44C…”, (pg. 7889): “…the interdomain disulfide bond (L:Q100C and H:G44C) evidently forms to stabilize the S5 scdsFv structure…”
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant application, to have modified the combined teachings of Yu et al., Ma et al., Koopmans et al., and Coloma et al. further in view of Paudel et al. and Huang et al. to generate a bispecific PD-L1/TIGIT IgG-scFv fusion, where the anti-TIGIT antibody is in the form of an scFv with the (GGGGS)5 linker with the VH G44C and VL Q100C mutations with a reasonable expectation of success, as Paudel et al. teaches this linker can be used in scFvs and Huang et al. teaches these stabilizing mutations. One would have been motivated to introduce the VH G44C and VL Q100C mutations to stabilize the anti-TIGIT scFv. Furthermore, Paudel et al. teaches that the (GGGGS)5 linker is an art-recognized linker structure to be used in scFvs, and one would have been motivated to use this linker in the anti-TIGIT scFv taught by Yu et al. and Paudel et al. to generate functional anti-TIGIT scFvs.
Introducing the VH G44C and VL Q100C mutations to the anti-TIGIT antibody scFv taught by Yu et al. in the format VH-(GGGGS)5-VL, where the VH and VL are Yu et al. SEQ ID NO: 9 and 10, respectively, would yield an amino acid sequence that is 100% identical to instant SEQ ID NO: 99 (i.e., the limitations of instant claim 65):
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQHVSTAVNWYQQKPGKAPKLLIYSASYLYSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQHVSTAVNWYQQKPGKAPKLLIYSASYLYSGVPS 60
Qy 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYITPYTFGCGTKLEIKGGGGSGGGGSGGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYITPYTFGCGTKLEIKGGGGSGGGGSGGG 120
Qy 121 GSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGYSITSDYAWIWIRQPPGKCLEW 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGYSITSDYAWIWIRQPPGKCLEW 180
Qy 181 IGYITSSGSTYYNPSLKSRVTFSVDTSKNQFSLKLSSVTAADTATYYCARLDFGNYGGAM 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 IGYITSSGSTYYNPSLKSRVTFSVDTSKNQFSLKLSSVTAADTATYYCARLDFGNYGGAM 240
Qy 241 DYWGQGTLVTVSS 253
|||||||||||||
Db 241 DYWGQGTLVTVSS 253
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 2, 3, 8, 9, 22, 26, 27, 40, 44 and 82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 30, 44, 45, 47, 49, 51, and 57-60 of copending Application No. 17/923,999 (herein App ‘999) in view of Ma et al. (Biochem Biophys Res Commun. 2020 Oct 15;531(2):144-151. doi: 10.1016/j.bbrc.2020.07.072. Epub 2020 Aug 8, supra).
App ‘999 claims anti-TIGIT antibodies including HB0030, which comprises the VH of SEQ ID NO: 9 and the VL of SEQ ID NO: 10 (claims 1 and 44). SEQ ID NO: 9 contains the HCDR1-3 sequences of instant SEQ ID NO: 3, 4, and 5 (i.e., the limitations of instant claims 2, 8, 9, and 22):
Qy 1 GYSITSDYA 9 1 ITSSGST 7
||||||||| |||||||
Db 1 QVQLQESGPGLVKPSETLSLTCTVSGYSITSDYAWIWIRQPPGKGLEWIGYITSSGSTYY 60
Qy 1 ARLDFGNYGGAMDY 14
||||||||||||||
Db 61 NPSLKSRVTFSVDTSKNQFSLKLSSVTAADTATYYCARLDFGNYGGAMDYWGQGTLVTVS 120
SEQ ID NO: 10 contains the LCDR1-3 sequences of instant SEQ ID NO: 6, 7, and 8 (i.e., the limitations of instant claims 3, 26, 27, and 40):
Qy 1 QHVSTA 6 1 SAS 3
|||||| |||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQHVSTAVNWYQQKPGKAPKLLIYSASYLYSGVPS 60
Qy 1 QQHYITPYT 9
|||||||||
Db 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYITPYTFGQGTKLEIK 107
App ‘999 additionally claims comprising the anti-TIGIT antibody and an acceptable adjuvant (claim 51).
App ‘999 does not claim bispecific anti-PD-L1 and anti-TIGIT bispecific antibodies (i.e., the limitations of instant claim 44)
Ma et al., in the same field of endeavor, teaches anti-TIGIT/anti-PD-L1 bispecific antibodies for dual checkpoint inhibition to activate T-cells for cancer treatment (Abstract): “…we demonstrated that the BsAb retained high blocking activity towards PD-1/PD-L1 or TIGIT/CD155 interaction. The BsAb synergistically enhanced T cell activities in vitro compared to two parental Nbs. Taken together, we obtained a multivalent BsAb blocking biological function of PD-L1 and TIGIT and it is worthy to further study the anti-tumor activities of this BsAb in vivo.”
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant application, to have modified the teachings of App ‘999 in view of Ma et al. to have incorporated the anti-TIGIT antibody of App ‘999 into a bispecific antibody that is also targeting PD-L1 with a reasonable expectation of success, as Ma et al. teaches such bispecific antibodies can be made and used to enhance T-cell activation. One would have been motivated to make this change for the purposes of making an anti-TIGIT/anti-PD-L1 bispecific antibody that targets both checkpoint inhibitors to synergistically enhance T-cell activation, as taught by Ma et al.
The invention encompassed by the instant claims are a prima facie obvious variant of the invention claimed by App ‘999 in view of Ma et al. This is a provisional double patenting rejection.
Claims 23 and 41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 30, 44, 45, 47, 49, 51, and 57-60 of copending Application No. 17/923,999 (App ‘999, supra) in view of Ma et al. (supra), as applied to claims 2, 3, 8, 9, 22, 26, 27, 40, 44 and 82, and further in view of Koopmans et al. (Oncoimmunology. 2018 May 31;7(8):e1466016. doi: 10.1080/2162402X.2018, supra) and Metz et al. (Protein Eng Des Sel. 2012 Oct;25(10):571-80. doi: 10.1093/protein/gzs064. Epub 2012 Sep 13, supra).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘999 in view of Ma et al., and further in view of Koopmans et al. and Metz et al. for the same reasons discussed for the 35 U.S.C. § 103 rejection supra. This is a provisional double patenting rejection.
Claims 59, 60, 68, and 69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 30, 44, 45, 47, 49, 51, and 57-60 of copending Application No. 17/923,999 (App ‘999, supra) in view of Ma et al. (supra), as applied to claims 2, 3, 8, 9, 22, 26, 27, 40, 44 and 82, and further in view of Koopmans et al. (supra) and Coloma et al (Nat Biotechnol. 1997 Feb;15(2):159-63. doi: 10.1038/nbt0297-159, supra).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘999 in view of Ma et al., and further in view of Koopmans et al. and Coloma et al. for the same reasons discussed for the 35 U.S.C. § 103 rejection supra. This is a provisional double patenting rejection.
Claims 65 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 30, 44, 45, 47, 49, 51, and 57-60 of copending Application No. 17/923,999 (App ‘999, supra) in view of Ma et al. (supra), Koopmans et al. (supra), and Coloma et al. (supra), as applied to claims 2, 3, 8, 9, 22, 26, 27, 40, 44 and 82, and further in view of Paudel et al. (J Biotechnol. 2017 Jun 10;251:47-52. doi: 10.1016/j.jbiotec.2017.04.002. Epub 2017 Apr 7, supra) and Huang et al. (J Biol Chem. 2010 Mar 12;285(11):7880-91. doi: 10.1074/jbc.M109.061457, supra).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘999 in view of Ma et al., and further in view of Koopmans et al. and Coloma et al. for the same reasons discussed for the 35 U.S.C. § 103 rejection supra. This is a provisional double patenting rejection.
Conclusion
No claim is allowed.
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/ALEC JON PETERS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641