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 1-3, 5, 7, 10, 34-36, 52, 62, 65-66 are amended. Claims 4, 6, 8-9, 11-33, 37-51, 53-61, 63-64, and 67-69 are cancelled. Claims -----1-3, 5, 7, 10, 34-36, 52, 62, 65-66 are currently pending and 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 02/16/2021, corresponding to application 63/150,006.
Information Disclosure Statement
The Information Disclosure Statements filed on 11/24/2025 have been considered.
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 1-3, 5, 7, 10, 34-36, 52, 62, and 65-66 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.
The claims either recite the phrase “or fragment thereof” or depend from claims that recite said phrase. The term “or fragment thereof” could be interpreted to mean, for example, only a single amino acid. The specification does not provide any examples of single amino acid agents that are capable of binding antigen, and as such the recitation of an anti-EGFR antibody or fragment thereof lacks adequate written description. This issue may be remedied by amending “or fragment thereof” to read “or antigen-binding fragment thereof.”
Also with respect to claims 36, 52, and 62, which recite methods of treating any cancer, it is noted that the specification provides support for treating cancers that express EGFR. - [0003] Epidermal growth factor receptor (EGFR) is overexpressed in many solid tumors including head and neck, colorectal and non-small cell lung cancer (NSCLC), and is a target of intense therapeutic interest and development. Absent empirical determination, one skilled in the art would be unable to readily envision which types of cancers that do not express EGFR may be treated using the claimed anti-EGFR antibodies. Furthermore the specification does not provide any examples of cancers that do not express EGFR that may be treated using the claimed anti-EGFR antibodies. This issue may be overcome by amending the claims to specify the treatment of an EGFR-expressing cancer.
Claim 52 is drawn to a method of treating cancer in a subject in need thereof, said method comprising administering to a subject a therapeutically effective amount of an anti-domain IV EGFR antibody.
The claims encompass a large number of anti-EGFR domain IV antibodies having diverse heavy and light chain CDR amino acid sequences. Following a review of the specification, it appears that Applicant has disclosed multiple anti-EGFR antibodies, see p. 2-7 of the specification; however in view of this disclosure, Applicant is claiming a broad genus of molecules that would be expected to encompass multiple anti- EGFR domain IV binding domains having diverse heavy and light chain CDR sequences. Even though Applicant has disclosed multiple 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 EGFR domain IV. 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 multiple species within the genus claimed; however given the substantial antibody structure variation within the genus, the disclosure of four 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 EGFR domain IV, because the instant specification does not provide structural antibody features that correlate with a functional ability to bind EGFR domain IV. 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 EGFR domain IV 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 EGFR domain IV.
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. Accordingly absent empirical determination, one skilled in the art would be unable to predict or envision which CDR residues of the described anti-EGFR antibodies could be changed such that the resultant variant CDR residues form an antigen-binding site capable of binding EGFR domain IV. 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 EGFR domain IV, and because the disclosed species 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 EGFR domain IV, 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.
(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.
Claim(s) 52, 62, and 65 are rejected under 35 U.S.C. 102a1 as being anticipated by Graeven et al (Graeven et al, British Journal of Cancer, 2006, 94, 1293-1299; published 04/04/2006), as evidenced by Schmiedel et al (Schmiedel et al, Cancer cell, 13, 365-373, 2008; published 04/2008).
At the Abstract, Graeven et al. disclose that “[t]The humanised anti-epidermal growth factor receptor (EGFR) monoclonal antibody matuzumab (formerly EMD 72000) is active against pancreatic cancer in preclinical studies.” Graeven et al teach that not all patients treated with Matuzumab had drug related adverse events (Graeven et al, Table 2). Furthermore, Graeven et al teach that 16 patients treated with matuzumab were EGFR high (positive) (Graeven et al, Table 1).
At p. 2 Schmeidel et al disclose that “[h]ere we describe the crystal structure of the Fab fragment of matuzumab (Fab72000) bound to a truncated form of the extracellular region of EGFR that comprises all of domain III plus the first 24 amino acids from domain IV.” As evidence by Schmeidel et al, matuzumab meets the limitation of an anti-domain IV EGFR antibody.
Conclusion
No claims are allowed.
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/J.K.D./Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642