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 .
Applicant’s amendment, filed on 4/18/2024, is acknowledged.
Claims 1-3, 5, 8-15, 20, 22-28, and 31-36 are cancelled.
Claims 4, 6, 7, 16-19, 21, 29, 30, and 37-46 are currently pending.
Claims 4, 21, and 29 are independent claims.
Election/Restrictions
Applicant’s election of Group I, claims 4, 6, 7, 16-19, 37, drawn to a single domain antibody that binds to VEGFA, and the species of: i) the CDR 1-3 of SEQ ID NO: 50-52, respectively; and ii) the FR1-4 of SEQ ID NO: 40, 41, 42, and 44, respectively in the reply filed on 4/13/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
As stated in the Restriction Requirement mailed on 2/11/2026, Groups I and III have Unity of Invention, and the method of Group III will be examined as well.
Please note that the separate product of Group II is not eligible for rejoinder.
Claims 21 and 38-42 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions and/or Species.
Claims 4, 6, 7, 16-19, 29, 30, 37, and 44-46 are under examination as reading on an anti-VFGFA single domain antibody and methods of treatment/prevention comprising administration of the antibody.
Priority
Applicant’s claim for the benefit of a prior-filed foreign application SG 10202101681W, filed February 19, 2021, is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/17/2023 and 2/06/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner in their entireties.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency 1 – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Amino acid sequences are disclosed in Figure 1 without the corresponding sequence identifiers in the figure or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specific deficiency 2 – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Amino acid sequences are disclosed in the following locations without the corresponding sequence identifiers:
pg. 50, lines 11-12 and 16-17
pg. 55, lines 13-14 and 17-18
pg. 61, lines 28-29
Additionally, nucleic acid sequences are disclosed in the following locations without the corresponding sequence identifiers:
Table 1
Table 2
Table 3
Table 5
Table 6
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The use of the term MaxiSorp™ (¶pg. 52, line 9; pg. 53, line 14; pg. 54, line 3; pg. 56, line 17; pg. 57, line 13 Tables 4, 7, 8), which is a trade name or 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.
Claim Objections
Claim 4 currently recites “VEGFA”, and claim currently recites “VEGFR”. These are readily recognized acronyms in the art, such as “DNA” for 5’-deoxyribonucleic acid. Please define the acronyms “VEGFA” and “VEGFR” when they are first used in the claims.
Claims 6 and 37 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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 4, 7, 16-19, 29, 30, and 43-46 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 enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
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 4, 7, 16-19, 29, 30, 45, and 46 encompass antigen binding molecules comprising, or methods of treating/preventing a disease comprising administration of a broad genus of single-domain antibodies comprising the elected species of CDRs with the recited function of “binds to VEGFA”, which contains unknown amino acid residues. The Sequence Table disclosed in the instant specification provides information on the claimed sequences:
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The genus of single-domain antibodies encompassed by the claims contains (3*2)(3*2*2)(2*2*2*2*2*2*3*2*3*2*2) ≈ 3.3x105 individual single-domain antibody structures, defined by their amino acid sequences especially in the CDR regions critical for binding, all with the function of “binds to VEGFA”.
Additionally, claims 29, 30, and 43-46 encompass methods of treating or preventing a disease in which VEGFA/VEGFR mediated signaling comprising administration of a large genus of antibodies with a partial structure at best and the function of “binds to VEGFA” as discussed supra (claims 29, 30, 45, and 46), or the narrower single-domain antibody species recited in claims 43 and 44.
The specification discloses generation of phage display libraries to screen for single-domain antibodies that bind to vascular endothelial growth factor A (VEGFA; Example 1). Each library had over 1010 clones (pg. 50, line 24) and were screened for individual single-domain antibody clones that can bind to VEGFA (Examples 2 and 3).
Amount of direction and existence of working examples:
The specification discloses identification of 10 different sdAb clones that bind to VEGFA: 13A6, 16A2.1, 16A6.1, 20A2.1, 20A3.1, 21A1.1, 21A8.1, 21D9.1, 21E6.1, 23D5.1 (Sequence Listing Table). Each of these antibody clones are specific antibody structures defined by their amino acid sequences, especially in the CDR regions, that have the structure of “binds to VEGFA”.
The instant specification does not disclose any methods of treating or preventing a disease in which VEGFA/VEGFR mediated signaling is pathologically implicated comprising administration of an anti-VEGFA single domain antibody.
Level of predictability, state of prior art, and quantity of experimentation needed:
Regarding the broadly claimed genus of antigen binding molecules with the function of “binds to VEGFA”, the claims are directed to a broad genus of single domain antibody binding agents with a partial structure at best all with the function of “binds to VEGFA”, which includes over 3x105 structures all 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 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 10 different anti-VEGFA single domain antibody examples with the function of “binds to VEGFA” that were found from screening a large library of candidates for specific binding.
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 a broad class of over 3x105 single domain antibodies with the function of “binds to VEGFA”, while the instant specification discloses 10 different examples of antibody structures with this function.
The instant claims are directed to classes of polypeptides that include “a ‘vast’ number” of additional structures (i.e., amino acid sequences of all of the CDR regions that are necessary for antigen binding in the case of antibodies) in which the instant specification fails to describe. It would be necessary to first generate and then screen each candidate agent to determine whether or not it met the function limitations of “binds to VEGFA”. 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 other antibody structures would have the function of “binds to VEGFA”. The only structure-function relationship guidance the specification provides is to disclose individual examples of antibody structures 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 as single domain antibodies that bind to VEGFA and a limited number of species with defined structures (e.g. amino acid sequences) to support an entire genus of diverse and structurally unrelated inhibitory polypeptide structures. Yet the instant specification does not provide sufficient guidance and directions as to the structural features of the single domain antibody structures 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.).
Regarding the claimed methods of treating or preventing a disease in which VEGFA/VEGFR-mediated signaling is pathologically implicated comprising administration of an anti-VEGFA antibody (claims 29, 30, and 43-46), the instant specification does not disclose any working example of a method of treating a disease comprising administration of one of the exemplary single-domain antibody structures disclosed in the specification.
The instant specification discloses VEGFA/VEGFR mediated signaling is implicated in many diseases (pg. 39, lines 11-19; pg. 40, line 35 to pg. 41, line 9), and discloses but does not exemplify that the disclosed single domain antibody structures can be used to treat or prevent diseases associated with VEGFA/VEGFR mediated signaling (pg. 42, lines 18-27), including cancers or all types (pg. 40, lines 5-27), non-cancerous ocular diseases (pg. 41, lines 26-33) and autoimmune diseases of all types (pg. 41, lines 35-41).
There are no structurally similar anti-VEGFA single-domain antibodies known in the art for treating such a broad genus of diseases as recited in the claims. While the instant specification suggests that the recited anti-VEGFA single-domain antibodies can be used to treat such diseases, this state of the prior art suggests a lack of predictability in this art which, taken with the fact that there is a lack of guidance with respect to dosages and a lack of working examples, leads to the conclusion that it would require undue experimentation to use the invention of claims 29, 30, and 43-46).
Furthermore, undue experimentation would be required to determine if the claimed single-domain antibody structures would be able to treat any and all diseases in which VEGFA/VEGFR signaling is pathologically implicated. For example, Pronto-Laborinho et al. (Biomed Res Int. 2014;2014:947513. doi: 10.1155/2014/947513) teaches that amyotrophic lateral sclerosis animal models have delayed loss of motor neurons when VEGFA is overexpressed, indicating that single-domain antibodies that bind to VEGFA may accelerate ALS instead of treating the disease (pg. 10): “Wang et al. crossed SOD1G93A mice with mice overexpressing VEGF-A in neurons. These double transgenic mice had a significant delay in motor neuron loss and in the onset of weakness, resulting in an increased survival compared to the single transgenic mice.”
Therefore, given the unpredictability in whether or not VEGFA inhibition would treat all diseases in which VEGFA/VEGFR signaling is implicated, undue experimentation would be required by one with ordinary skill in the art to treat any and all diseases in which VEGFA/VEGFR signaling is pathologically implicated.
Regarding the methods of preventing a disease in which VEGFA/VEGFR mediated signaling is pathologically implicated, the burden of enabling the prevention of a disease (i.e. the need for additional testing) would be greater than that of enabling a treatment due to the need to screen those mammals susceptible to such diseases and the difficulty of proof that the administration of the drug was the agent that acted to prevent the condition. Further, the specification does not provide guidance as to how one skilled in the art would go about screening those patients susceptible to diseases in which VEGFA/VEGFR signaling is pathologically implicated within the scope of the presently claimed invention. Nor is sufficient guidance provided as to a specific protocol to be utilized in order to prove the efficacy of the presently claimed anti-VEGFA single-domain antibodies in preventing diseases in which VEGFA/VEGFR signaling is pathologically implicated. The specification does not show that an anti-VEGFA single-domain antibody being injected prior to a subject having a disease in which VEGFA/VEGFR signaling is pathologically implicated.
The specification does not reasonably provide enablement to make and use the invention of instant claims 4, 7, 16-19, 29, 30, and 43-46.
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 4, 7, 16-19, 29, 30, 45, and 46 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 4 and 29 recite single domain antibody sequences incorporating amino acid sequences using sequence identifiers containing sequences with variable residues. Each of SEQ ID NO: 50, 51, 52, 54, 55, and 56 contain at least one variable amino acid without a recitation of which amino acid residue(s) are in each variable position. It is currently unclear if the variable positions can be any amino acid residue, or a more limited set such as the positions disclosed in the specification. Dependent claims 7, 16-19, 30, 45, and 46 do not define these positions and are also rejected as indefinite. For the purposes of examination, the undefined amino acid positions are interpreted to be limited to the residues recited in the specification. For example, the specification recites single domain antibodies comprising the CDR1 of SEQ ID NO: 50, wherein the first undefined positions in SEQ ID NO: 50 is P, S, or A and the second undefined positions is D or E.
To resolve this issue, it is recommended to amend independent claims 4 and 29 to recite the specific residues found in each undefined amino acid position.
Claim 7 is indefinite because it depends on claim 1 which recites single domain antibody CDR sequences, however SEQ ID NO: 20 is only 20 amino acid residues in length and does not comprise three different CDRs: DRADSVGYNVIFPGSTYSRSG. It is currently unclear how this sequence contains one of the CDR sets recited in instant claim 4.
Claim 30 recites: “[t]he methods according to claim 29, wherein the disease is selected from:…”. This claim is interpreted as a Markush claim (MPEP § 2173.05(h)):
“Treatment of claims reciting alternatives is not governed by the particular format used (e.g., alternatives may be set forth as "a material selected from the group consisting of A, B, and C" or "wherein the material is A, B, or C"). See, e.g., the Supplementary Examination Guidelines for Determining Compliance with 35 U.S.C. 112 and for Treatment of Related Issues in Patent Applications ("Supplementary Guidelines"), 76 Fed. Reg. 7162, 7166 (February 9, 2011). Claims that set forth a list of alternatives from which a selection is to be made are typically referred to as Markush claims, after the appellant in Ex parte Markush, 1925 Dec. Comm’r Pat. 126, 127 (1924). The listing of specified alternatives within a Markush claim is referred to as a Markush group or Markush grouping. Abbott Labs v. Baxter Pharmaceutical Products, Inc., 334 F.3d 1274, 1280-81, 67 USPQ2d 1191, 1196-97 (Fed. Cir. 2003) (citing to several sources that describe Markush groups)…
…A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. If a Markush grouping requires a material selected from an open list of alternatives (e.g., selected from the group "comprising" or "consisting essentially of" the recited alternatives), the claim should generally be rejected under 35 U.S.C. 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim. See In re Kiely, 2022 USPQ2d 532 at 2* (Fed. Cir. 2022) (each independent claim recites "a selection from the group comprising a person, an animal, an animated character, a creature, an alien, a toy, a structure, a vegetable, and a fruit." … (emphasis added). "Given the breadth of variation among the specified alternatives and the use of the open-ended word ’comprising’ to define the scope of the list, we affirm the Board's conclusion that the pending claims recite improper Markush language and are indefinite under § 112(b).").”
The Markush grouping recited in claim 30 does not recite a closed list of alternatives and is therefore rejected as indefinite. To resolve this issue, it is recommended to amend the claim to recite “…wherein the disease is selected from the group consisting of: …”.
Additionally, regarding instant claim 30, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 30 recites multiple cases of broad genera of diseases followed by a narrower subgenus of diseases and even individual disease species encompassed by the broad genus. For example, the claim recites the broad genus “a cancer”, which includes any cancer, followed by the narrower subgenera “a VEGFA-expressing cancer”, “a VEGFR-expressing cancer”, and the narrower species of “ocular tumor”. Claim additionally recites the broad genus of “ocular disease”, followed by a subgenus of ocular disease “retinopathy” and the narrower species of “diabetic retinopathy”. This is also the case for the broad genus “macular degeneration” and the narrower subgenre “age-related macular degeneration” and “wet age related macular degeneration”. The claim further recites the broad genus of “autoimmune disease” and the narrower species “rheumatoid arthritis”, “psoriasis”, and “multiple sclerosis”. Claim 30 further recites the broad genus “arthritis” and the narrower species “rheumatoid arthritis” and “osteoarthritis”.
The claims is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. To resolve this issue, it is recommended to amend the claim to recite either one broad disease species for each disease type, or a list of non-overlapping subgenre or species of diseases.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Kazemi-Lomedasht et al. (Mol Immunol. 2015 May;65(1):58-67. doi: 10.1016/j.molimm.2015.01.010. Epub 2015 Jan 30. PMID: 25645505.) teaches anti-VEGFA nanobodies Nb22, Nb23, Nb35 and Nb42 (abstract). However, anti-VEGFA antibodies with the sequences recited in instant claim 4 is not taught.
Co-pending application 18/277,738 teaches an anti-VEGFA nanobodies, however the nanobodies comprise different CDR amino acid sequences to the elected species of nanobody of the instant application.
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/ALEC JON PETERS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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