DETAILED ACTION
1. The present application is being examined under the pre-AIA first to invent provisions.
2. Applicant’s amendment filed on November 3, 2025 is acknowledged.
Claims 1-161, 163, and 164 have been canceled.
Claims 162 and 165-171 are pending.
Claims 169-171 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on March 7, 2025.
Claims 162 and 165-168 are currently under consideration as they read on the elected invention.
3. In view of applicant’s amendment, following rejections are set forth.
4. 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.
5. Claims 162 and 165-168 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 for the reasons of record.
The amended claims are now drawn to a method for selecting at least batch of a drug product comprising an antibody or antibody fragment having an Fc receptor-binding moiety having at least one mechanism of action mediated through binding to the Fc receptor via contacting with an Fc receptor and measuring the binding to the Fc receptor, and selecting the antibody or antibody fragment thereof which has equal to or greater binding to the Fc receptor compared to the reference standard, wherein the reference standard and the antibody are two different batches of the same antibody.
The specification discloses that antibody (e.g. anti-CD4 antibody) exhibits better binding affinity to FcγRIII having reduced sialic acid (e.g. see Example 18 on pages 68-69) and binding to the Fcγ receptors including FcγRI and FcγRIIIa correlates to antibody Fc mediated ADCC function (e.g. see Example 17 on page 68).
There is insufficient written description in the specification as-filed of a drug product comprising an FcR binding peptide and an Fc receptor as recited in the instant claims.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant states:
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Thus, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
Contrary to applicant’s reliance on the working examples 14-18, note that most of the examples show that less binding (rather than equal to or greater binding) when compared to the reference standard antibody that is requires for the newly added step (g) in independent claim 162.
For example, the instant specification discloses when compared to reference batch MRS-CD4-001, most batches bound to a lower amount to cell-bound FcγRI with high variations (e.g. see Examples 15, 16, FIGs. 13, and 14 in the specification as-filed).
The specification discloses:
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As stated previously, the claims recite a genus a drug product comprising an FcR binding peptide and Fc receptor as part of the invention without providing a physical structure or testable functional activity for the Fc binding peptide and Fc receptor and fragments thereof that retains the ability to bind an Fc region.
Applicant has disclosed that certain specific antibody, e.g. anti-CD4 antibody exhibits better affinity to FcγRIII in vitro having reduced sialic acid and binding to Fcγ receptors FcγRI and FcγRIIIa correlates to antibody Fc region mediated ADCC function.
Thus Applicant has disclosed only a limited species of the drug product comprising an FcR binding peptide and Fcγ receptor namely IgG antibody that binds specific antigen (e.g. CD4) and specific Fcγ receptors such as FcγRIIIa.
The claimed drug product comprising an FcR binding peptide and Fc receptor including fragments there of that retains the ability to bind an Fc region lack a common structure essential for their function and the claims do not require any particular structure basis or testable functions be shared by the instant drug product and Fc receptor for selecting antibody having equal or greater binding for the Fc receptor.
Regarding the carbohydrate structure on FcγRIIIa, Ferrara et al. (JBC 2006,
281;8:5032-5036, reference on IDS) teach that removal of carbohydrate at FcγRIIIa’s Asn-162 increases affinity for native IgG but reduces affinity for glycoengineered antibodies (e.g. see left column on page 5032).
It does not appear based upon the limited disclosure of IgG1 antibody and FcγRIIIa with reduced sialic acid content or FcγRI alone that Applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the limited number of species disclosed and the extensive variation permitted within the genus of drug product and Fc receptor.
“Adequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Regents of the University of California v. Eli Lilly and Co. 43 USPQ2d 1398 (Fed. Cir. 1997).
The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter of the claim. Id. 43 USPQ2d at 1406.
In the absence of disclosure of relevant, identifying characteristics of the drug product comprising an FcR binding peptide and Fc receptor, there is insufficient written disclosure under 35 U.S.C. 112, first paragraph.
6. Claims 162 and 165-168 are rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the enablement requirement. The claim(s) contains 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.
The amended claims are now drawn to a method for selecting at least batch of a drug product comprising an antibody or antibody fragment having an Fc receptor-binding moiety having at least one mechanism of action mediated through binding to the Fc receptor via contacting with an Fc receptor and measuring the binding to the Fc receptor, and selecting the antibody or antibody fragment thereof which has equal to or greater binding to the Fc receptor compared to the reference standard, wherein the reference standard and the antibody are two different batches of the same antibody.
The specification discloses that antibody (e.g. anti-CD4 antibody) exhibits better binding affinity to FcγRIII having reduced sialic acid (e.g. see Example 18 on pages 68-69) and binding to the Fcγ receptors including FcγRI and FcγRIIIa correlates to antibody Fc mediated ADCC function (e.g. see Example 17 on page 68).
However, 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.
Applicant’s arguments have been fully considered but have not been found persuasive. Applicant asserts that the specification discloses working examples using antibodies and Fc receptors and assays known in the art to measure their binding, in e.g. [129]-[134] of the published instant application. As such, applicant asserts that the claims are enabled.
This is not found persuasive for following reasons:
Contrary to applicant’s reliance on the working examples 14-18, note that most of the examples show that less binding (rather than equal to or greater binding) when compared to the reference standard antibody that is requires for the newly added step (g) in independent claim 162.
For example, the instant specification discloses when compared to reference batch MRS-CD4-001, most batches bound to a lower amount to cell-bound FcγRI with high variations (e.g. see Examples 15, 16, FIGs. 13, and 14 in the specification as-filed).
The specification discloses:
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The specification has not provided sufficient guidance and directions as to how to determine the potency of any or all drug product comprising an FcR binding peptide solely based upon the binding of the FcR binding peptide to any or all Fc receptor in general or an Fc receptor that has reduced sialic acid.
The claims do not recite sufficient structural elements or specificity for the drug product and Fc receptor encompassed by the claimed methods for selecting the antibody which has equal or greater binding for the Fc receptor compared to the reference standard antibody. The specification does not provide sufficient guidance and direction to identify and to enable the method of determining the potency of a drug product comprising an Fc binding polypeptide based on the binding of the Fc polypeptide to an or all Fc receptor and wherein the method is part of an application for marketing authorization for selling said drug produce as a pharmaceutical composition.
Regarding the carbohydrate structure on FcγRIIIa, Ferrara et al. (JBC 2006,
281;8:5032-5036, reference on IDS) teach that removal of carbohydrate at FcγRIIIa’s Asn-162 increases affinity for native IgG but reduces affinity for glycoengineered antibodies (e.g. see left column on page 5032).
There is insufficient objective evidence that the assay to evaluate the potency of specific therapeutic antibody, e.g. anti-CD4 IgG1 antibody binding to specific Fc receptor such as FcγRIIIa with reduced sialic acid, as disclosed in the specification as-filed, can be extrapolated to predict the method of selecting at least one batch of drug product comprising an antibody based on determining the binding of the Fc containing polypeptide and any or all Fc receptor including FcRn, and selecting the antibody having equal to or greater binding to the Fc receptor compared to the reference standard antibody.
As such, applicant’s arguments have not been found persuasive.
7. 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. Claims 162 and 165-168 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-104 of US 9,580,506 (the ‘506 Patent, reference on IDS) for the reasons of record.
Applicant requests that the rejection be held abeyance. As such, the nonstatutory double patenting rejection is maintained for the reasons of record.
9. No claim is allowed.
10. THIS ACTION IS MADE FINAL. 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.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
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.
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/CHUN W DAHLE/Primary Examiner, Art Unit 1641