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 .
DETAILED ACTION
Status of the Claims
1. Claims 1-56 are the original claims filed 2/8/2023. In the Preliminary Amendment of 8/1/2023, Claims 1, 4, 8-10, 12, 14, 15, 17, 19-21, 23, 39, 41, 43-44, 46, and 52 are amended and claims 2, 3, 5-7, 11, 16, 22, 24-38, 40, 42, 45, 47-51, and 53-56 are cancelled. In the Response of 8/18/2025, claims 1, 4, 18 and 44 are amended and claims 20-21 and 23 are canceled. Claims 1, 4, 8-10, 12-15, 17-19, 39, 41, 43-44, 46 and 52 are all the claims.
Amendment of the claims raises new grounds for rejection. The Office Action is final.
Priority
2. USAN 18/166,202, filed 02/08/2023, is a Divisional of 16/319,235, filed 01/18/2019, now U.S. Patent # 11629193, and having 2 RCE-type filing therein,
16/319,235 is a National Stage entry of PCT/EP17/68261, International Filing Date: 07/19/2017, claims foreign priority to United Kingdom 1612520.5, filed 07/19/2016.
Information Disclosure Statement
3. As of 10/14//2025, a total of two (2) IDS is filed: 8/1/2023; and 8/18/2025. The corresponding initialed and dated 1449 form is considered and of record.
Withdrawal Objections
Specification
4. The objection to the abstract of disclosure because it includes speculative application(s), i.e., “are expected” is withdrawn by way of deletion of the phrase.
5. The objection to the disclosure because of informalities is withdrawn. Both clean and marked-up copies of the specification are provided in the Response of 8/18/2025.
a) The amended specification rectifies the improper use of the term, e.g., ATCC, Chemstation, BIAcore, HuMax, which is a trade name or a mark used in commerce.
b) The amended specification rectifies the objection to Table 1 on p. 33 in view of the inclusion of the sequence identifiers for the polynucleotide primers having a length of > 10 nucleic acids as pursuant to 37 C.F.R. 1.821-1.825.
Claim Objections
6. The objection to Claim 18 because of informalities is withdrawn.
a) Claim 18 is amended to recite “the sequence set forth in SEQ ID NO: 49”.
Withdrawal of Rejections
Claim Rejections - 35 USC § 112(b)
7. The rejection of Claims 4 and 44 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn.
a) Claim 4 is amended to recite “TYG
b) Claim 44 is amended to recite "[the] a recombinant host cell comprising a nucleic acid encoding the specific binding member.”
Rejections Maintained
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.
8. The rejection of Claims on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11629193 (IDS 8/1/2023) is maintained for the pending claims and moot for the canceled claims.
a) Applicants allege the amendment to the claims to recite the negative proviso “wherein the specific binding member does not comprise a CDR-based antigen binding site” finds support in canceled claim 20.
Response to Arguments
Applicants’ comments and the amendment to claim 1 are dispositive to the original limitation found in instant canceled claim 20. Claim 20 in the claim set of 8/1/2023 literally requires (“further comprises”) the presence of CDR(s) in the specific binding member:
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b) Applicants allege in citing MPEP § 2173.05(i) that "[i]f alternative elements are positively recited in the specification they may be explicitly excluded in the claims."
Response to Arguments
Claim interpretation
The claims are now interpreted based on the alternative elements positively recited in the specification that are explicitly excluded by the negative proviso.
“antigen binding site”: the specification does not teach alternatives to anything other than a CDR-based antigen binding site:
[0042] In addition to the EGFR antigen-binding site in the CH3 domain, the specific binding member of the invention may further comprise one or more additional antigen-binding sites to create a bi- or multi-specific molecule. Preferably, the specific binding member comprises a CDR-based antigen-binding site. CDR based antigen binding sites are found in the variable regions of naturally-occurring immunoglobulin molecules and their structure is well-known in the art. Where the specific binding member comprises a CDR-based antigen binding site, the specific binding member is preferably an antibody molecule. The antibody molecule is not particularly limited, provided that it comprises a CH3 domain, as herein defined, and a CDR-based antigen-binding site. In a preferred embodiment, the antibody molecule is a human immunoglobulin G molecule, such as a human IgG1, IgG2, IgG3 or IgG4 molecule, more preferably a human IgG1 molecule. The sequences of human immunoglobulin G molecules are known in the art and introducing a CH3 domain or CH3 domain sequence as disclosed herein into such a molecule would not present any difficulty to the skilled person.
[0091] A specific binding member according to the present invention may comprise a second antigen-binding site, preferably a CDR-based antigen-binding site. The term “CDR-based antigen-binding site” refers to the antigen-binding site of a specific binding member variable region which is composed of six CDR residues.
In the response, Applicants have not identified the examples (“alternative elements”) of non-CDR based, antigen-binding sites that are taught in the original specification and that fall within the meaning of the negative proviso.
c) Applicants allege in citing In re Johnson the specification teaches the specific binding member may further comprise a CDR- based antigen-binding site, [therefore] the specification "necessarily described the part remaining.”
Response to Arguments
Where as in the present case, the specification does not teach or support any alternatives to a CDR-based antigen binding site, the negative proviso does not satisfy the fact pattern of In re Johnson. The only part remaining in the specification is the CDR-based antigen binding site that is positively disclaimed by the amendment.
The rejection is maintained.
9. The rejection of Claims on the ground of nonstatutory double patenting over claims 1-14 of U.S. Patent No. 12312408 (formerly copending Application No. 18/451,047 (reference application US 20240132599)) is maintained for the pending claims and moot for the canceled claims.
The reference application is not afforded safe harbor protection under 35 USC 121 because it does not share continuity nor a restriction/speciation with the instant claims.
Applicants re-iterate the amendment to the claims now recites the negative proviso “wherein the specific binding member does not comprise a CDR-based antigen binding site”. The reference claims do not disclose a molecule comprising an EGFR antigen-binding site that does not comprise a CDR-based antigen binding site.
Response to Arguments
Applicants’ comments and the amendment to claim 1 are dispositive to the original limitation found in instant canceled claim 20. Claim 20 in the claim set of 8/1/2023 requires (“further comprises”) the presence of CDR(s) in the specific binding member:
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b) Applicants allege in citing MPEP § 2173.05(i) that "[i]f alternative elements are positively recited in the specification they may be explicitly excluded in the claims."
Response to Arguments
Claim interpretation
The claims are now interpreted based on the alternative elements positively recited in the specification that are explicitly excluded by the negative proviso.
“antigen binding site”: the specification does not teach alternatives to anything other than a CDR-based antigen binding site:
[0042] In addition to the EGFR antigen-binding site in the CH3 domain, the specific binding member of the invention may further comprise one or more additional antigen-binding sites to create a bi- or multi-specific molecule. Preferably, the specific binding member comprises a CDR-based antigen-binding site. CDR based antigen binding sites are found in the variable regions of naturally-occurring immunoglobulin molecules and their structure is well-known in the art. Where the specific binding member comprises a CDR-based antigen binding site, the specific binding member is preferably an antibody molecule. The antibody molecule is not particularly limited, provided that it comprises a CH3 domain, as herein defined, and a CDR-based antigen-binding site. In a preferred embodiment, the antibody molecule is a human immunoglobulin G molecule, such as a human IgG1, IgG2, IgG3 or IgG4 molecule, more preferably a human IgG1 molecule. The sequences of human immunoglobulin G molecules are known in the art and introducing a CH3 domain or CH3 domain sequence as disclosed herein into such a molecule would not present any difficulty to the skilled person.
[0091] A specific binding member according to the present invention may comprise a second antigen-binding site, preferably a CDR-based antigen-binding site. The term “CDR-based antigen-binding site” refers to the antigen-binding site of a specific binding member variable region which is composed of six CDR residues.
In the response, Applicants have not identified the examples (“alternative elements”) of non-CDR based, antigen-binding sites that are taught in the original specification and that fall within the meaning of the negative proviso.
c) Applicants allege in citing In re Johnson the specification teaches the specific binding member may further comprise a CDR- based antigen-binding site, [therefore] the specification "necessarily described the part remaining.”
Response to Arguments
Where as in the present case, the specification does not teach or support any alternatives to a CDR-based antigen binding site, the negative proviso does not satisfy the fact pattern of In re Johnson. The only “part remaining” in the specification is the CDR-based antigen binding site that is positively disclaimed by the amendment.
The rejection is maintained.
New Grounds for Rejection
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.
Written Description
10. Claims 1, 4, 8-10, 12-15, 17-19, 39, 41, 43-44, 46 and 52 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.
Claim 1 and the dependent claims thereof recite a negative proviso.
The specification and the priority documents do not provide literal or actual support for this limitation. In the response of 8/18/2025, Applicants cite support for the negative proviso in Claim 20 in the claim set of 8/1/2023 that requires (“further comprises”) the presence of CDR(s) in the specific binding member:
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MPEP 706.03(m) states in part "New matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. See MPEP § 608.04 to § 608.04(c).
The use of a negative limitation is used to define the invention in terms of what it is not, rather than distinctly and particularly claiming “alternative elements” of non-CDR based, antigen-binding sites. Under MPEP 2173.05(i) “Any negative limitation or exclusionary proviso must have basis in the original disclosure.”
In the decision from Santarus, Inc. et al., v. Par Pharmaceutical, Inc., Case No. 10-1360 (Fed. Cir., Sept. 4, 2012), the Court stated that negative limitations are adequately supported when the specification describes a reason to exclude the relevant limitation. Such written description support need not even rise to the level of a disclaimer> (In re Santarus where the claim was drawn to a method for treating an acid-caused gastrointestinal disorder by administering to a subject suffering from such disorder a solid composition of omeprazole and sodium bicarbonate,”wherein the composition contains no sulfacrate.” The specification taught that “omeprazole represented an advantageous alternative to the use of H2 antagonists, antacids and sulfacrate as a treatment for complications related to stress-related mucosal damage.”)
Scope of Enablement
11. Claim 52 is 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 treating a cancer with the specific binding member Fcab clones FS1-60 (SEQ ID NO: 1 and 3), FS1-65 (SEQ ID NO 8) and FS1-67 (SEQ ID NO: 13 or 14); and Fcab clone constructs comprising a CDR-based antigen binding site, does not reasonably provide enablement for just any antigen binding site in association with the Fcab clones to treat any cancer, in vivo. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to using the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required, are summarized in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability of the art, the breadth of the claims, the quantity of experimentation which would be required in order to practice the invention as claimed.
Claim interpretation
Claim 52 is drawn to a method of treating any EGFR-expressing cancer in any patient comprising administering a therapeutically effective amount of the specific binding member of claim 1.
The claims are interpreted based on the alternative elements positively recited in the specification that are explicitly excluded by the negative proviso.
“antigen binding site”: the specification does not teach alternatives to anything other than a CDR-based antigen binding site:
[0042] In addition to the EGFR antigen-binding site in the CH3 domain, the specific binding member of the invention may further comprise one or more additional antigen-binding sites to create a bi- or multi-specific molecule. Preferably, the specific binding member comprises a CDR-based antigen-binding site. CDR based antigen binding sites are found in the variable regions of naturally-occurring immunoglobulin molecules and their structure is well-known in the art. Where the specific binding member comprises a CDR-based antigen binding site, the specific binding member is preferably an antibody molecule. The antibody molecule is not particularly limited, provided that it comprises a CH3 domain, as herein defined, and a CDR-based antigen-binding site. In a preferred embodiment, the antibody molecule is a human immunoglobulin G molecule, such as a human IgG1, IgG2, IgG3 or IgG4 molecule, more preferably a human IgG1 molecule. The sequences of human immunoglobulin G molecules are known in the art and introducing a CH3 domain or CH3 domain sequence as disclosed herein into such a molecule would not present any difficulty to the skilled person.
[0091] A specific binding member according to the present invention may comprise a second antigen-binding site, preferably a CDR-based antigen-binding site. The term “CDR-based antigen-binding site” refers to the antigen-binding site of a specific binding member variable region which is composed of six CDR residues.
In the response of 8/18/2025, Applicants have not identified the examples (“alternative elements”) of non-CDR based, antigen-binding sites that are taught in the original specification and that fall within the meaning of the negative proviso.
The negative proviso is interpreted as precluding a CDR-based antigen binding site comprising the specific binding member. The specific binding member is construed as comprising only the EGFR antigen-binding site in the CH3 domain: Fcab clones FS1-60; SF1-65 and FS-1-67.
Disclosure in the Specification
The demonstration of a therapeutic effect for the claimed Fcab clones on any EGFR-expressing cancer is shown in: Example 10: anti-EGFR Fcab therapy in adenocarcinoma model LXFA 677 for all 3 Fcabs (Figure 4; Table 5).
Examples 11-21 describe the generation of an “anti-EGFR mAb2“ bispecific molecule where despite the antigen binding site of the negative proviso in claim 52, the antigen binding site comprises CDR-based anti-CTLA4 or anti-HGF antibody domains.
The specification provides limited disclosure for a Fcabs of instant claim 1 being cancer-therapeutic for a single type of cancer (Example 10). The specification provides disclosure for the Fcab constructs comprising a CDR-based antigen binding site (Examples 11-21).
The scope of the claims must bear a reasonable correlation with the scope of enablement. See In re Fisher, 166 USPQ 19, 24 (CCPA 1970). "[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.'" Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365 (Fed. Cir. 1997) (quoting In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993)).
The Patent Act requires that patent applicant describes the invention in explicit terms to enable any person skilled in the art to make and use the invention. 35 U.S.C. 112. Applicants seek over potentially millions of CH1/CL modified antibodies than the specification teaches how to produce. The enablement requirement is a crucial aspect of the patent “bargain”: an inventor is granted limited protection from competition in exchange for publicly disclosing their new technology. See the decision in Morse, Incandescent Lamp, and Holland Furniture, establishing the requirement that if a patent claims an entire class or genus of processes, machines, or compositions of matter, the specification must enable a person skilled in the field to make and use the entire class. If 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. In other words, the specification must enable the full scope of the invention as defined by its claims. The more one claims, the more one must enable. See §112(a); see also Continental Paper Bag Co. v. Eastern Paper Bag Co., 210 U. S. 405 (1908) (“[T]he claims measure the invention.”)
Conclusion
12. No claims are allowed.
13. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu Julie can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643