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 .
Claims 1-9, 11-12, 15-18, 20, 24-25, and 29 are pending and are under examination.
Claim interpretation
The recitation of CDR1 consisting of “an amino acid sequence represented by SEQ ID NO: 2”, for example, is being interpreted as requiring SEQ ID NO: 2 as the CDR1. In other words, the sdAb of the instant claims includes a CDR1 consisting of SEQ ID NO: 2, CDR2 consisting of SEQ ID NO: 3, and CDR3 consisting of SEQ ID NO: 4.
Claims 2-9, 11-12, 15-18, 20, 24-25, and 29 are objected to for the following informalities: The dependent claims refer to the antibody or “an” antigen-binding fragment thereof according to, for example, claim 1. Correction to recite “the antibody or the antigen-binding fragment thereof” , or to recite “the antibody or antigen-biding fragment thereof:” according to, for example, claim 1 is required.
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.
Claims 2-9, 11-12 and 29 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 2 is indefinite in the recitation that the sdAb includes the following “VHH domain”, and then listing various framework region sequences. The claim is unclear because the listed sequences are not VHH domains, but rather framework regions. For example, it is not clear what structure, other than the recited framework sequences, would be required to meet the limitation of “the following VHH domain”. Amendment to recite, “wherein the sdAb includes: FR1 consisting of an amino acid sequence represented by SEQ ID NO: 6;… and FR4 consisting of an amino acid sequence represented by SEQ ID NO: 9”, for example, would be remedial.
Claim 4 is indefinite in the recitation of the antibody or antigen binding fragment of claim 1 “comprising at least one or more amino acid substitutions”. The only recites sequences in claim 1 are the CDRs of SEQ ID NO: 2-4. However, if the claim is to be interpreted as encompassing substitutions to SEQ ID NO: 2 and 4, claim 4 would not be a proper dependent claim since it would not require all the limitations of the claim from which it depends. If the claim is intending to encompass non-CDR substitutions, it is not clear what the substitutions would be relative to, since the reset of the antibody is generically claimed. The scope of the claim is unclear and indefinite. Claims 5-6 and 12 are indefinite for the same reasons.
Claim 29 is directed to a method for detecting CD47 or determining an amount of CD47 in a sample, but recites no limitations using any reagent that would bind to or detect CD47. The claimed method steps recite contacting with an antibody of claim 1, which is PD-L1 binding antibody, and detecting binding to PD-L1. It is not clear how the method would detect CD47.
Regarding claim 7, the phrase "preferably" 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). For example, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 7 recites the broad recitation fusing to an Fc fragment, and the claim also recites preferably fusing via a peptide linker, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 4-6 and 12 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 3-6 and 12 appear to encompass amino acid substitutions in the sequences of the claim from which they depend, i.e. SEQ ID Nos 2-4 or 5 and 11. Therefore, they do not require all the limitations of the claim from which they depend, since claims 1 and 11require SEQ ID NO: 2-4, or 5 and 11. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-9, 11-12, 15-18, 20, 24-25, and 29 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 CDR1 consisting of an amino acid sequence represented by SEQ ID NO: 2; CDR2 consisting of an amino acid sequence represented by SEQ ID NO: 3; and CDR3 consisting of an amino acid sequence represented by SEQ ID NO: 4; a method for treating cancer, the method comprising administering the antibody or the antigen-binding fragment thereof to an individual; and a method for detecting PD-L1 or determining an amount of PD-L1 in a sample with said antibody or antigen binding fragment thereof;
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 CDR1 consisting of an amino acid sequence represented by SEQ ID NO: 2; CDR2 consisting of an amino acid sequence represented by SEQ ID NO: 3; and CDR3 consisting of an amino acid sequence represented by SEQ ID NO: 4., a method of preventing cancer, or a method of detecting CD47 or determining an amount of CD47 in a sample.
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.
Claims 24-25 encompass preventing cancer. However, preventing or curing cancer is extremely unpredictable due the heterogeneous nature of the disease, the difficulty in identifying at risk individuals, and the numerous challenges in effective treatment (see for example, Carey, 2010). Thus, it would be highly unpredictable as to whether an antibody therapy could be used to prevent cancer, as is encompassed by the instant claims.
Furthermore, claim 29 is directed to detecting CD47 with a PD-L1 binding antibody, which would be highly unpredictable, since it would not bind to CD47.
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.
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 1-9, 11-12, 15-18, 20, 24-25, and 29 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.
Claims 1-9, 11-12, 15-18, 20, 24-25, and 29 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.
No claim is allowed. The claims are free of the prior art, because the prior art does not teach or suggest a sdAb having SEQ ID Nos: 2-4 as CDR1, CDR2, and CDR3, respectively.
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