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 .
Status of Claims
Claims 1, 4, 7-8, 12, 15-21, 23-26, 29-31, 33, and 35-38 are amended. Claims 27-28 are cancelled. Claim 39 is added. Claims 1-26 and 29-39 are currently pending. Claims 1-26, 38, and 39 are under examination.
Priority
Applicant' s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The claims have an earliest effective filing date of 12/21/2021, corresponding to application Netherlands 2030198.
Information Disclosure Statement
The Information Disclosure Statements filed on 01/05/2023, 03/29/2023, and 08/18/2025 have been considered.
Election/Restriction
Applicant has elected the glycosylation component of claim 2 with traverse. Applicant asserts that the elected antibody binds to the glycosylated epitopes recited in the claims. This argument has been considered and is deemed not persuasive. The glycosylation modifications have different chemical structures and different biological functions. As such the requirement to elect a particular glycosylation is maintained.
Claims 3, 6, 11, 14, 29-37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/27/2026.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Regarding claim 38, the phrase "optionally" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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, 2, 4, 5, 7-10, 12, 13, 15-26, and 38-39 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Claim 1 is drawn to a binding domain that binds a MUC1 peptide comprising the amino acid sequence of SEQ ID NO: 249, wherein the threonine (T) residue at position 14 of the MUC1 peptide comprises a-GalNAc glycosylation or Neu5Ac-a(2-6)-GalNAc glycosylation.
Claim 16 is drawn to a binding domain that binds a MUC1 peptide comprising specific heavy chain CDRs or variants thereof having one to three substitutions.
Claim 18 is drawn to a binding domain that binds a MUC1 peptide comprising specific light chain CDRs or variants thereof having one to three substitutions.
Claim 19 is drawn to the binding domain according to claim 16, wherein the binding domain comprises a light chain variable region having the amino acid sequence of SEQ ID NO: 218, or having at least 80%, sequence identity thereto.
The claims encompass a large number of anti-MUC1 antibodies having diverse heavy and light chain CDR amino acid sequences. Following a review of the specification, it appears that Applicant has disclosed fifty-two anti-MUC1 binding domains, specifically, those defined in pages 70-76 of the specification each encompassing the light chain of SEQ ID NO: 218. However in view of this disclosure, Applicant is claiming a broad genus of molecules that would be expected to encompass multiple anti-MUC1 binding domains having diverse heavy and light chain CDR sequences. Even though Applicant has disclosed fifty-two species within said genus, the specification does not provide adequate written description for the entire claimed genus, because one skilled in the art would be unable to immediately envision, recognize, or distinguish at least most of the members comprised within the genus claimed, specifically, which light and heavy chain CDR sequences (and combinations of said CDR sequences) give rise to antibody molecules capable of binding MUC1. As detailed below Applicant’s disclosure is not sufficient to demonstrate possession of the entire claimed genus, and as such Applicant’s disclosure does not satisfy the written description requirement of 35 U.S.C. 112(a).
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. In the instant case, Applicant has disclosed fifty-two species within the genus claimed. However given the substantial antibody structure variation within the genus, as well as the high level of unpredictability in the art, the disclosure of fifty-two species comprised within the claimed genus is not sufficiently representative of the entire genus.
Furthermore Applicant has not disclosed relevant, identifying characteristics of CDR region amino acid sequences (or combinations thereof) that confer upon an antibody the ability to bind MUC1, because the instant specification does not provide structural antibody features that correlate with a functional ability to bind MUC1. To elaborate on why the claimed antibodies lack adequate written description, Mariuzza (Annu. Rev. Biophys. Biophys. Chem., 16: 139-159, 1987) reviews the structural basis of antigen-antibody recognition and teach that naturally occurring conventional antibodies comprise two polypeptides, the so-called light and heavy chains. The antigen-combining site of an antibody is a three-dimensional structure that fully comprises six CDRs, three each from the light and heavy chains. The amino acid sequences of the CDRs are hypervariable, as the amino acid residues contained within the CDRs determine much of the antibody’s antigen-binding specificity. In view of Mariuzza, it is apparent that antibodies having less than all six CDRs that form the antigen binding site of a conventional antibody in their proper context of heavy and light chain variable domains do not describe the particularly identifying structural feature of the antibody that correlates with the antibody’s ability to bind antigen. Absent a description of the at least minimal structural features correlating with a functional ability to bind MUC1 which are shared by members of a genus commonly sharing this function, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish which heavy and light chain CDR amino acid sequences (or combinations thereof) may be combined such that the resultant heavy and light chain variable regions comprise six CDRs that confer the ability to bind MUC1.
Furthermore while the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains. For example in a series of experiments involving a monoclonal antibody to Legionella pneumophilia serotype 1, McCarthy et al. (J. Immunol. Methods, 251(1-2): 137-149, 2001) demonstrated that a single VH CDR3 substitution of tyrosine to serine at position 95 resulted in the total loss of antigen recognition in an ELISA. Lin et al. (African Journal of Biotechnology, 10(79):18294-18302, 2011) teach that a single amino acid substitution in the VL CDR3 of an anti-avian infectious bronchitis virus (IBV) single-chain antibody (ZL.80) may abrogate binding. For example at Figure 3, Lin et al. demonstrate that replacing either the Cys105 or Asp106 residue in the VL CDR3 of ZL.80 with an alanine residue reduces binding to near negative control levels. Lin et al. also teach that some single amino acid substitutions in the VL CDR3 of ZL.80 may significantly improve binding. For example replacing the Val108 residue in the VL CDR3 of ZL.80 with a tyrosine residue results in a 12.9-fold increase in affinity compared to parental ZL.80. Accordingly absent empirical determination, one skilled in the art would be unable to predict or envision which CDR residues could be changed such that the resultant variant CDR residues form an antigen-binding site capable of binding MUC1. The general knowledge and level of skill in the art does not adequately supplement the omitted description, because specific, not general, guidance is needed. Since the disclosure fails to describe relevant, identifying structural characteristics, in the form of heavy and light chain CDR amino acid sequences, that correlate with the ability to bind MUC1, and because the fifty-two disclosed species detailed above are not sufficient to describe the claimed genus, it is submitted that the written description requirement of 35 U.S.C. 112(a) has not been met.
Although screening techniques can be used to isolate CDR variant antibodies that possess the ability to bind MUC1, Applicant is reminded that the written description requirement of 35 U.S.C. 112 is severable from the enablement provision. As stated in Vas-Cath Inc. v. Mahurkar (CA FC) 19 USPQ2d 1111, 935 F2d 1555, “The purpose of the ‘written description’ requirement is broader than to merely explain how to ‘make and use’; the applicant must also convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.”
Accordingly given the unpredictability associated with antibody CDR region changes on antigen binding and given the lack of particularity with which the claimed antibodies are described in the specification, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish at least most of the members of the genus to which the claims are directed, and therefore the specification would not reasonably convey to the skilled artisan that Applicant was in possession of the claimed invention at the time the application was filed.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-2, 4-5, 8-10, 12-13, 15, 20-22, 25, 26, 38, and 39 are rejected under 35 U.S.C. 102a1 as being anticipated by Schoen et al (WO2015009740; published 01/22/2015).
Schoen et al teach binding domains capable of binding MUC1 peptide of (SEQ ID NO: 345), which comprises 100% sequence identity of instant SEQ ID NO: 249 (see Example 3). Schoen et al further teach the MUC1 peptide wherein the threonine (T) residue at position 14 of the MUC1 peptide comprises a-GalNAc glycosylation and wherein the serine (S) residue at position 15 of the MUC1 peptide comprises a-GalNAc glycosylation (Schoen et al, pg. 71, Example 3). Therefore Schoen et al meets the limitations of claims 1-2, 4-5, 9-10, 12-13, and 38.
Regarding claim 8, Schoen et al teach the antibody may specifically bind MUC1 (Schoen et al, pg. 24, paragraph 4-5).
Regarding claims 8 and 15, Schoen teach binding determined by a glycopeptide array (Schoen et al pg. 72, Table 3)
Regarding claim 20, Schoen et al teach the binding domain may be a Fab. (Schoen et al pg. 26, paragraph 2)
Regarding claim 21, Schoen et al teach the binding moiety may comprise two binding domains (Schoen et al, pg. 25, paragraph 3)
Regarding claim 22, Schoen et al teach the binding moiety may be an IgG1 or IgG4. (Schoen et al, pg. 35, paragraph 3)
Regarding claim 25, the effects of the binding domain are inherent to the structure. Therefore, the limitations of the binding domain of Schoen et al described above meet the limitations of claim 25.
Regarding claim 26, Schoen et al teach a pharmaceutical composition which may comprise a pharmaceutically acceptable carrier. (Schoen et al, pg. 61 paragraph 3 and pg. 64, paragraph 1)
Regarding claim 39, Schoen et al teach a pharmaceutical composition with an effective amount of binding moiety and pharmaceutically acceptable carrier. (Schoen et al, pg. 61 paragraph 3 and pg. 64, paragraph 1)
Conclusion
No claim is allowed.
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/J.K.D./Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
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