DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's amendment and remarks, filed 5/4/26, are acknowledged.
Claims 1-3, 7-9, 11, 15-18, 20, 24-25, 29-30 are pending.
In view of Applicant’s claim amendments, only the following rejections remain.
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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, 7-9, 11, 15-18, 20, 24-25, 29-30 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:
An antibody or antigen binding fragment thereof comprising a single domain antibody (sdAb) that specifically binds to PD-L1, wherein the sdAb includes a CDR1 consisting of the amino acid sequence of SEQ ID NO: 2; a CDR2 consisting of the amino acid sequence of SEQ ID NO: 3; and a CDR3 consisting of the amino acid sequence of SEQ ID NO: 4;
does not reasonably provide enablement for:
An antibody comprising a single domain antibody (sdAb) that specifically binds to PD-L1; or an antigen-binding fragment thereof, wherein the sdAb includes a CDR1 consisting of the amino acid sequence of SEQ ID NO: 2; a CDR2 consisting of the amino acid sequence of SEQ ID NO: 3; and a CDR3 consisting of the amino acid sequence of SEQ ID NO: 4;
The specification disclosure is insufficient to enable one skilled in the art to practice the invention as claimed without an undue amount of experimentation. Undue experimentation must be considered in light of factors including: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill in the art, the level of predictability of the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention, in re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
“The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling (MPEP 2164.03)” The MPEP further states that physiological activity can be considered inherently unpredictable.
Claim 1 is directed to an antibody comprising a sdAb, wherein the sdAb includes a defined CDR1-3, or an “antigen biding fragment thereof”. In other words, only the antibody comprising the sdAb is required to have the CDRs of SEQ ID NO: 2-4, and the sdAb or CDRs are not required for the “antigen-binding fragment thereof”. For example, the claims would encompass any fragment of an antibody comprising the sdAb with CDRs of SEQ ID NO; 2-4, which could read on a single CDR fragment, or an antigen binding fragment with a single CDR from the sdAb having SEQ ID NO: 2-4. Claims 4-6 and 12 also appear to encompass CDR substitutions. The state of the art is such that heavy chain only sdAab antibodies can be produced, but that the 3 CDRs of an sdAb are critically involved in antigen binding, that even single amino acid changes can alter antigen specificity of binding, and that CDR mutations are unpredictable in terms of affinity, specificity, and solubility, and are also context dependent (see Hall, 1992, and Rabia, 2018). Thus, making and using the genus of antigen biding antibody fragments as broadly claimed would be highly unpredictable.
Thus, based on the breadth of the claims and the unpredictability of the art, the instant specification must provide a sufficient and enabling disclosure, commensurate in scope with the instant claims. No guidance is provided regarding antibody fragments that have less than a sdAb with three CDRs of SEQ ID NO: 2-4 are disclosed. Likewise, no examples or guidance are provided regarding prevention of cancer, or for using the claimed PD-L1 binding antibodies to detect CD47.
Thus, based on the unpredictability of the art, the breadth of the claims, and the lack of guidance provided by the instant specification, it would require undue experimentation to make and use antibodies as broadly claimed.
Applicant’s arguments filed 5/4/26 have been fully considered, but they are not persuasive.
Applicant argues that it well established that antigen specificity is determined by CDR sequences and the ordinary artisan would recognize that an antibody comprising specific CDRs would be expected to bind to the same target antigen. Applicant argues that antigen binding fragments could be produced with the same antigen binding properties by including the same CDR sequences.
The present claims do not require the antigen binding fragment include the CDR sequences, which is what is argued by Applicant as the enabled subject matter.
The claims recite an antibody comprising a single domain antibody or an antigen binding fragment thereof, where “the sdAb” comprises CDRs of SEQ ID NO: 2-4. Only the sdAb is required to have the claimed CDRs, not the antigen binding fragment thereof. For example, the claims would encompass any antigen binding fragment of an a single domain antibody comprising CDRs of SEQ ID NO: 2-4, which would encompass a fragment comprising a single CDR. Amendment as noted in the heading of the enablement rejection would be remedial. Alternatively, Applicant could amend claim 1 to recite an single domain antibody or an antigen binding fragment thereof that specifically binds to PD-L1, wherein the sdAb and the antigen binding fragment thereof include a CDR1 consisting of the amino acid sequence of SEQ ID NO: 2; a CDR2 consisting of the amino acid sequence of SEQ ID NO: 3; and a CDR3 consisting of the amino acid sequence of SEQ ID NO: 4. This would make clear that the antigen binding fragment also must comprise the CDRs of SEQ ID NO; 2-4.
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.
Claims 1-3, 7-9, 11, 15-18, 20, 24-25, 29-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 8-10, 12-17, 19-20, 23, 25, 29-30 of copending Application No. 18/277,931 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘931 application claims a bispecific antibody that comprises a first sdAb that comprises CDR1-3 of SEQ ID Nos: 2-4, which are identical to CDRs of SEQ ID NO: 2-4 of the instant claims. Therefore, the bispecific antibody is a species of antibody within the scope of the instant claims. The ‘931 application claims the same FR1-FR4 and that the sdAb has SEQ ID NO: 1, which is identical to SEQ ID NO: 1 of the instant application. The ‘931 claims the bispecific has a HcAb with an Fc fragment from IgG1 that is monomeric or multimeric. The ‘931 publication discloses that said HcAb with Fc IgG1 comprise SEQ ID NO: 5, which is identical to SEQ ID NO: 5 of the instant application. Thus, the HcAb of the ‘931 application cover the same HcAb of the instant claims. The ‘931 application claims said bispecific also comprises an antigen binding domain that binds CD47 (i.e. a second epitope) and claims said bispecific antibody conjugated to an immunomodulator, conservative or non-genetically encoded substitutions, and a nucleic acid encoding the antibody. The ’931 application also claims a method of treating cancer, such as melanoma, comprising administering the antibody. Furthermore, using the bispecific antibody to detect whether PD-L1 or CD47 are in a sample would be obvious to monitor treatment and would be well within the purview of the ordinary artisan.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s statement that the rejection be held in abeyance until the time of allowance is acknowledged.
Claims 1-3, 7-9, 11, 15-18, 20, 24-25, 29-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/951,146 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘146 application claims a bispecific antibody that comprises a first sdAb that comprises CDR1-3 of SEQ ID Nos: 2-4, which are identical to CDRs of SEQ ID Nos: 2-4 of the instant claims. Therefore, the bispecific antibody is a species of antibody within the scope of the instant claims. The ‘146 application claims the bispecific has a HcAb of with an Fc fragment from IgG1 that is monomeric or multimeric. The ‘146 publication discloses that said HcAb with Fc IgG1 comprise SEQ ID NO: 5, which is identical to SEQ ID NO: 5 and comprises SEQ ID NO: 1 of the instant application. Thus, the HcAb of the ‘146 application cover the same HcAb and sdAb of the instant claims. The ‘146 application claims said bispecific further comprises a antigen binding domain that binds CD47 (i.e. a second epitope) and claims said bispecific antibody conjugated to an immunomodulate, conservative or non-genetically encoded substitutions, and a nucleic acid encoding the antibody. The ’146 application also claims a method of treating cancer, such as melanoma, comprising administering the antibody. Furthermore, using the bispecific antibody to detect PD-L1 or CD47 binding in a sample would be obvious to monitor treatment and would be well within the purview of the ordinary artisan.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant argues that the double patenting rejection should be withdrawn if it is the only rejection remaining.
The rejection is maintained since the claims stand rejected under other grounds.
No claim is allowed.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 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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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
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