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 .
Restriction/Election
Applicant’s election without traverse of Group I (i.e., claims 1-6) in the reply filed on 7 April 2026 (referred to herein as Remarks) is acknowledged.
Status of the Claims
Claims 1-15 were originally filed 16 January 2023 and the preliminary amendments filed the same day and 24 July 2023 have been entered. Claims 8-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7 April 2026.
Claims 1-6 and under consideration.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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 (e.g., see specification pg. 6, line 14). See MPEP § 608.01.
Claim Objections
Claims 1, 2, 5, and 6 are objected to because of the following informalities:
Claim 1 recites, “CDR1, CDR2, and CDR3” in line 3 and should recite, “complementarity determining region (CDR) 1, CDR2, and CDR3”.
Claim 2 recites, “FR1, FR2, FR3, and FR4” in line 1 and should recite, “framework region (FR) 1, FR2, FR3, and FR4”.
Claim 5 recites, “encoding an antibody” in line 1 and should recite, “encoding the antibody”.
Claim 6 recites, “an antibody according” in line 3 and should recite, “the antibody according”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
A neutralizing anti-interleukin 11 receptor alpha subunit (IL11Rα) antibody comprising HCDRs 1-3 comprising Seq ID NOs: 1, 2 and 3, respectively and LCDRs 1-3 comprising Seq ID Nos: 4-6 (see claim 1), comprising VH FR1, FR2, FR3, and FR4 comprising Seq ID Nos: 7-10 and VL FR1, FR2, FR3, and FR4 comprising Seq ID Nos: 11-14 (see claim 2), and a VH comprising Seq ID No: 15 and a VL comprising Seq ID NO: 16 (see claim 3),
does not reasonably provide enablement for
“functional equivalent variants thereof” (see claim 1 lines 4-5 and 8-9, claim 2 lines 2-4 (recited 2 times), and claim 3 lines 2-4 (recited 2 times)). 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 In re Wands (858 Fed 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, limited working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to make and use the claimed invention.
Claims 1-3 are drawn to anti-IL11Rα antibodies comprising particular sequences and “functional equivalent variants thereof” (see claim 1 lines 4-5 and 8-9, claim 2 lines 2-4 (recited 2 times), and claim 3 lines 2-4 (recited 2 times)). The specification defines a functional equivalent variant as having substantially similar sequence identity with it and substantially maintaining its capacity to bind to the target (see specification para spanning pgs. 9-10). In addition, the specification discloses a functional equivalent variant also encompasses polypeptide sequences derived from said sequence and may comprise the addition, deletion or substitution of one or more amino acids (see specification para spanning pgs. 9-10). The specification also discloses the functional equivalent variant can have at least 70% sequence identity and the boundaries of the CDRs can consist of 1 or more additional/deleted amino acids at the N-terminus or C-terminus (see specification pg. 10, last para). Functionally the variant maintains at least 70% binding capacity to IL11Rα assessed by affinity, avidity, specificity, and/or selectivity (see specification pg. 11, 1st full para). The specification discloses similar definitions for the functional equivalent variants regarding the framework regions, VH, and VL sequences (see specification pg. 11, 2nd full para-pg. 12, 2nd para (framework), pg. 12, 3rd and 4th para (VH and VL)). Therefore, claims 1-3 are drawn to a genus of anti-IL11Rα antibodies comprising any CDR, framework region, VH and VL with at least 70% specificity for the target assessed using a variety of variables (e.g., avidity).
Applicant has disclosed a single anti-IL11Rα antibody (i.e., LAU490A) comprising HCDRs 1-3, LCDRs 1-3, VH, and VL comprising Seq ID Nos: 1-16 (see specification pg. 3, 1st para, pg. 67, last full para, pg. 70 last two para).
The state of the art teaches CDR sequences are the residues required for antigen binding and these sequences are highly variable in order to facilitate binding to a multitude of antigens (see Kapingidza et al. 2020. Antigen-Antibody Complexes. Vertebrate and Invertebrate Respiratory Proteins, Lipoproteins and other Body Fluid, CH 19, pgs. 465-484, pg. 468, lines 1-4). Culang also teaches that CDRs are widely assumed to be responsible for antigen recognition (see Culang et al. The structural basis of antibody-antigen recognition. Front. In Immun. 2013. Vol. 4, Article 302, abstract). The state of the art also teaches the mutation effects at interfaces are often unpredictable and more often than not result in decreased binding affinity (see Clark et al. Influence of canonical structure determining residues on antibody affinity and stability. Journal of Structural Biology 185 (2014) 223–227, pg. 223, 2nd col. 1st full para). Amino acids within the CDR regions can have cooperative effects, for example, substitutions in the AQC2 antibody of M32L in LCDR1 when paired with a conservative substitution Y70F retains nearly wildtype affinity compared to pairing with V29I where nearly all binding affinity was lost, or a M32I substitution when parried with A25F resulted in no binding (see Clark, Table 1, pg. 223, 2nd col. 1st full para). Similarly, Brown demonstrated using the example of a T15 antiphosphocholine Ab where only 1 of 15 antibodies with a single mutation loss antigen binding while 16 of 31 antibodies with 2-4 mutations loss antigen binding (see Brown et al. Tolerance to Single, but Not Multiple, Amino Acid Replacements in Antibody VH, CDR2. J Immunol (1996) 156 (9): 3285–3291.pg. 3285, 1st col. 1st para, Table 1, pg. 3290 1st col. last para). Therefore, a person of ordinary skill in the art would understand that as little as two substitutions in the CDR regions of an antibody can result in a complete loss of binding for the target.
Accordingly, in absence of substantive direction or guidance in the instant specification, the scope of experimentation required to develop antibodies with 1 or more substitutions at any position to any amino acid in the CDR/FR/VH/VL regions or additions to the N or C terminus with any amino acid in the CDR/FR/VH/VL regions and identify those that retain at least 70 specificity to IL11Rα is left to those skilled in the art. Given the unpredictability in altering a single amino acid or combinations thereof, the present claims and disclosure amount to an invitation to the skilled artisan to develop such embodiments. The skilled artisan would reasonably conclude that such experimentation would be unnecessarily, and improperly, extensive and undue.
Claims 1-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-3 are drawn to anti-IL11Rα antibodies comprising particular sequences and “functional equivalent variants thereof” (see claim 1 lines 4-5 and 8-9, claim 2 lines 2-4 (recited 2 times), and claim 3 lines 2-4 (recited 2 times)). The specification defines a functional equivalent variant as having substantially similar sequence identity with it and substantially maintaining its capacity to bind to the target (see specification para spanning pgs. 9-10). In addition, the specification discloses a functional equivalent variant also encompasses polypeptide sequences derived from said sequence and may comprise the addition, deletion or substitution of one or more amino acids (see specification para spanning pgs. 9-10). The specification also discloses the functional equivalent variant can have at least 70% sequence identity and the boundaries of the CDRs can consist of 1 or more additional/deleted amino acids at the N-terminus or C-terminus (see specification pg. 10, last para). Functionally the variant maintains at least 70% binding capacity to IL11Rα assessed by affinity, avidity, specificity, and/or selectivity (see specification pg. 11, 1st full para). The specification discloses similar definitions for the functional equivalent variants regarding the framework regions, VH, and VL sequences (see specification pg. 11, 2nd full para-pg. 12, 2nd para (framework), pg. 12, 3rd and 4th para (VH and VL)). Therefore, claims 1-3 are drawn to a genus of anti-IL11Rα antibodies comprising any CDR, framework region, VH and VL with at least 70% specificity for the target assessed using a variety of variables (e.g., avidity).
Applicant has disclosed a single anti-IL11Rα antibody (i.e., LAU490A) comprising HCDRs 1-3, LCDRs 1-3, VH, and VL comprising Seq ID Nos: 1-16 (see specification pg. 3, 1st para, pg. 67, last full para, pg. 70 last two para). There is no evidence from the disclosure that anti-IL11Rα antibodies with substitutions, deletion, or additions of any kind in the CDRs, FR, VH or VL were made. As stated above, the CDRs are integral for antigen binding (see above; Kapingidza pgs. 465-484, pg. 468, lines 1-4; see Culang abstract). Mutational effects on interfaces are often unpredictable(see Clark pg. 223, 2nd col. 1st full para).
Therefore, a person of ordinary skill in the art at the time of filling would understand residues within the CDRs are integral to antigen binding or maintaining the structure of the region that binds to the antigen and substitutions, additions, or deletions in these regions would affect one or both these attributes. As there is no art-recognized correlation between structure and function, it would be impossible for one of ordinary skill in the art to predict which CDRs or subsequent VH and VL sequences would result in a structure that binds IL11Rα. Overall, based on the disclosure, the state of the art at the time of filing, a skilled artesian would have recognized that the applicant was not in possession of the claimed invention at the time of filing.
Claim Rejections - 35 USC § 112(b)
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 1-6 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the CDR1, CDR2 and CDR3" in lines 3 and 6. There is insufficient antecedent basis for this limitation in the claim (see allowable subject matter below for suggested language).
Claim 2 recites the limitation "the FR1, FR2, FR3 and FR4” in lines 1 and 3. There is insufficient antecedent basis for this limitation in the claim (see allowable subject matter below for suggested language).
Claims 1-3 are drawn to “functionally equivalent variants”. The specification defines “functionally equivalent variants” as those with “substantially similar sequence identity” (see specification pg. 9, last para). Substantially is a relative term and therefore it is unclear at what degree of sequence similarity is a sequence considered a functionally equivalent variant.
Claim 5 is drawn to “said expression vector of aspect” in line 3. It is unclear what is within the scope of an “aspect”.
A broad limitation together with a narrow 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 5 recites the broad recitation a nucleic acid encoding an antibody according to claim 1, and the claim also recites and expression vector expressing the nucleic acid or host cell expressing either the nucleic acid or the expression vector which is the narrower statement of the limitation. The claim(s) are 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.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cook (see US Patent Publication 20190389957 A1, referred to herein as Cook, as cited on the IDS received 3 March 2023 pg. 2 US Patent Publications #1).
Claims 1-3 are drawn to anti-IL11Rα antibodies with particular HCDRs 1-3 (i.e., Seq ID Nos: 1-3; see claim 1), LCDRs 1-3 (i.e., Seq ID Nos: 4-6; see claim 1), VH FR1-4 (i.e., Seq ID Nos: 7-10; see claim 2), VL FR1-4 (i.e., Seq ID Nos: 11-14; see claim 2), VH (i.e., Seq ID No: 15; see claim 3) and VL (i.e., Seq ID No: 16; see claim 3) or “functionally equivalent variants”. The specification defines a functional equivalent variant as having substantially similar sequence identity with it and substantially maintaining its capacity to bind to the target (see specification para spanning pgs. 9-10). In addition, the specification discloses a functional equivalent variant also encompasses polypeptide sequences derived from said sequence and may comprise the addition, deletion or substitution of one or more amino acids (see specification para spanning pgs. 9-10, emphasis added). The specification also discloses the functional equivalent variant can have at least 70% sequence identity and the boundaries of the CDRs can consist of 1 or more additional/deleted amino acids at the N-terminus or C-terminus (see specification pg. 10, last para). Functionally the variant maintains at least 70% binding capacity to IL11Rα assessed by affinity, avidity, specificity, and/or selectivity (see specification pg. 11, 1st full para). The specification discloses similar definitions for the functional equivalent variants regarding the framework regions, VH, and VL sequences (see specification pg. 11, 2nd full para-pg. 12, 2nd para (framework), pg. 12, 3rd and 4th para (VH and VL)). Therefore, claims 1-3 are drawn to a genus of anti-IL11Rα antibodies comprising any CDR, framework region, VH and VL with at least 70% specificity for the target assessed using a variety of variables (e.g., avidity) and any degree of sequence similarity.
Cook discloses anti IL-11Rα antibodies comprising HCDRs/LCDRs 1-3 comprising Seq ID Nos: 18-24 (see Cook pgs. 38-39), VH FR1-4 and VL FR1-4 comprising Seq ID Nos: 28-51 (see Cook pgs. 39-40), and VH and VL sequences comprising Seq ID Nos: 7-17 (see Cook pg. 38). Cook discloses the antibodies effectively bind IL11Rα and reduce the percentage of activated fibroblasts in unstimulated cultures (see Cook pg. 47 para [0691-0693], pg. 48 para [0695 and 0697]). The antibody has sequence similarity to the instantly claimed CDRs. For example, Cook discloses HCDR1 in Seq ID No: 18 which comprises a tyrosine in position 2 and a histidine in position 5 which is identical to the instantly claimed Seq ID No: 1. This is pertinent to instant claims 1-3. Cook discloses the antibodies can be humanized (see Cook pg. 6 para [008]; see instant claim 4) and conjugated to a chemical moiety in the form of an antibody drug conjugate (see Cook pg. 15 para [0279]; see claim 6). In addition, Cook discloses nucleic acids encoding the antibody, expression vectors and host cells comprising said nucleic acids (see Cook pg. 2 para [0040-0044]).
Allowable Subject Matter
The following claims 1-6 drafted by the examiner and considered to distinguish patentably over the art of record in this application, presented to applicant for consideration:
Claim 1. A neutralizing antibody which specifically recognizes the interleukin 11 receptor alpha subunit (IL11RA) extracellular domain, wherein said antibody comprises:
a heavy chain variable region (VH) wherein the heavy chain complementarity determining region (HCDR) 1, HCDR2 and HCDR3 of the VH comprise, respectively, SEQ ID NOs: 1, 2 and 3, and
a light chain variable region (VL) wherein the light chain complementarity determining region (LCDR) 1, LCDR2 and LCDR3 of the VL region comprise respectively, SEQ ID NOs: 4, 5, and 6.
Claim 2. Cancelled.
Claim 3. The antibody according to claim 1, wherein the VH region comprises SEQ ID NO: 15 and the VL region comprises SEQ ID NO: 16 thereof.
Claim 5. A nucleic acid encoding the antibody according to claim 1.
Claim 6. An antibody-drug conjugate (ADC) comprising:
a therapeutic agent, and
the antibody according to claim 1.
Claim 20. (New) An expression vector comprising the nucleic acid according to claim 5.
Claim 21. (New) A host cell comprising the expression vector of claim 20.
Conclusion
No claim allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HILARY ANN PETRASH whose telephone number is (703)756-4630. The examiner can normally be reached Monday-Friday 8:30-4:30 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at (571)-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/H.A.P./Examiner, Art Unit 1644
/AMY E JUEDES/Primary Examiner, Art Unit 1644
Prosecution Insights