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 .
Application Status
The Response to the Election of Species Requirement, filed December 2, 2025, is entered. Applicant's election without traverse of the anti-CD47 antibody or antigen-binding fragment thereof comprising a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 50, which comprises three CDRs comprising the amino acid sequences of SEQ ID NO: 14, 17, and 23, respectively, and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 65, which comprises three CDRs comprising the amino acid sequences of SEQ ID NO: 30, 32, and 34, respectively, is acknowledged.
Claims 1-15, filed August 23, 2023, are pending and under examination herein.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. However, support for the claimed invention cannot be determined because the foreign priority documents provided are not in English. Therefore, the instant application is not entitled to the benefit of the foreign priority date of July 31, 2020.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e). Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Accordingly, the filing date of the PCT/CN2021/109446 application, filed on July 30, 2021, will be used for the purpose of applying prior art.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1 references Table 1 in parts (a)-(c). MPEP § 2173.05(s) states: “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table ‘is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.’ Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).” In the present case, the table recites heavy chain CDR amino acid substitutions based on their position in the HCDRs, which could be incorporated into the claims to define the invention.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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 1-4, 6-8, and 11-15 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.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the 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. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991).
MPEP § 2163 states that 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, or it may be satisfied by the 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. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species. Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For example, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875 (Fed. Cir. 2011).
The claimed invention. The nature and scope of the claimed invention first at issue is an antibody or antigen-binding fragment that specifically binds to CD47 as recited in claim 1, comprising “one or more” of:
a VH CDR1 which is “a variant of SEQ ID NO: 14 having 1-3 amino acid substitutions shown in Table 1”,
a VH CDR2 which is “a variant of SEQ ID NO: 17 having 1-3 amino acid substitutions shown in Table 1”,
a VH CDR3 which is “a variant of SEQ ID NO: 23 having 1-3 amino acid substitutions shown in Table 1”,
a VL CDR1 comprising “any one of [the] amino acid sequences set forth in SEQ ID NOs: 30-31”,
a VL CDR2 comprising “any one of [the] amino acid sequences set forth in SEQ ID NOs: 32-33”, and
(f) a VL CDR3 comprising “any one of [the] amino acid sequences set forth in SEQ ID NOs: 34-35”.
These claim limitations fail to satisfy the written description requirement because the claimed antibody or antigen-binding fragment does not comprise a complete structure (i.e., three heavy chain CDRs and three light chain CDRs) that would be expected to carry out the instantly claimed function of specifically binding to CD47 as understood by one of ordinary skill in the art and in view of Applicant's disclosure. Furthermore, the instantly claimed heavy chain CDRs comprise a level of sequence variation (“1-3 amino acid substitutions”) that would be expected to alter the antigen-binding properties of the instantly claimed antigen-binding proteins in an unpredictable manner, and the light chain CDRs could be “mixed and matched” in such a way that would not result in a functional antigen-binding protein as required by the instant claims.
Further at issue is an antibody or antigen-binding fragment that specifically binds to CD47 as set forth in claim 2 (and dependent claims 3-8 and 10-15), comprising “one or more” of:
a VH CDR1 comprising “any one of [the] amino acid sequences set forth in SEQ ID NOs: 14-16”,
a VH CDR2 comprising “any one of [the] amino acid sequences set forth in SEQ ID NOs: 17-22”,
a VH CDR3 comprising “any one of [the] amino acid sequences set forth in SEQ ID NOs: 23-29”,
a VL CDR1 comprising “any one of [the] amino acid sequences set forth in SEQ ID NOs: 30-31”
a VL CDR2 comprising “any one of [the] amino acid sequences set forth in SEQ ID NOs: 32-33”, and
a VL CDR3 comprising “any one of [the] amino acid sequences set forth in SEQ ID NOs: 34-35”.
These claim limitations fail to satisfy the written description requirement because (1) by the recitation that the claimed antibody or antigen-binding fragment comprises “one or more” of the CDRs, the claim does not recite a complete structure (i.e., three heavy chain CDRs and three light chain CDRs) that would be expected to carry out the instantly claimed function of specifically binding to CD47 as understood by one of ordinary skill in the art and in view of Applicant's disclosure, and (2) the claim recites that the CDRs can be “mixed and matched”, but not all possible combinations of the CDRs would be expected to result in a functional antigen-binding protein as required by the instant claims except for those specifically enumerated in the disclosure.
Claim 3 further recites that the antibody or antigen-binding fragment comprises a heavy chain variable region (VH) having an amino acid sequence “having at least 90% sequence identity to an amino acid sequence of any one of SEQ ID NOs: 11, 36-44, 50 and 56”, and claim 7 similarly sets forth that a VH having an amino acid sequence “having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 11 or 50”. These limitations allow for up to 10% sequence variability in the VH region, wherein the CDRs in said VH region are all not expressly defined in view of the limitations previously set forth in claim 2. Furthermore, these limitations allow significant variability in the corresponding VL region sequence. Conversely, claim 4 further recites that the antibody or antigen-binding fragment comprises a light chain variable region (VL) having an amino acid sequence “having at least 90% sequence identity to an amino acid sequence of any one of SEQ ID NOs: 12-13, 45-49, 51-55 and 65”, and claim 8 similarly sets forth a VL having an amino acid sequence “having at least 90% sequence identity to an amino acid sequence of any one of SEQ ID NOs: 13, 45-49, 51-55 and 65”. These limitations for up to 10% sequence variability in the VL region, wherein the CDRs in said VL region are all not expressly defined in view of the limitations previously set forth in claim 2. Furthermore, the claims allow significant variability in the corresponding VH region sequence.
State of the prior art. It is well established in the art that the formation of an intact antigen-binding site in an antibody usually requires the association of the complete heavy and light chain variable regions of a given antibody, each of which comprises three CDRs (or hypervariable regions) that provide the majority of the contact residues for the binding of the antibody to its target epitope. See Almagro (Frontiers in Immunology (2018) 8: 1751), “The IgG Molecule” (page 3) and Figure 1. Sela-Culang (Frontiers in Immunology (2013) 4: 302) further teaches, “A major focus in analyzing the structural basis for [antigen] recognition has been in identifying the exact boundaries of the CDRs in a given [antibody]. It is a common practice to identify paratopes through the identification of CDRs” (page 3).
Although the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is aptly 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. Ni (The Protein Journal (2024) 43: 683-696) teaches, “Mutations, even one mutation, introduced in the CDRs through [somatic hypermutation] can change the binding properties and repertoire of antibodies. However, how just one-point mutation can dramatically change the recognition profiles of the antibody is still unclear” (Introduction). Furthermore, while affinity maturation techniques can result in differences in the CDRs of the antibody compared to its parental antibody, those techniques involve trial-and-error testing and the changes that maintain or improve affinity are not predictable a priori (Almagro, pages 3 and 6-7).
Gershoni (Biodrugs (2007) 21(3): 145-156) teaches that antibody binding to the same antigen, or even the same epitope on that antigen, can be accomplished with an impressively wide variety of antibody structures, even when the antibodies are limited to those from a particular source (page 146, Section 1.1). The skilled artisan therefore understands that antibodies from a variety of different sources may bind the same antigen and even mediate the same functional effects, but differ widely in the details of the structure of their antigen-binding sites, particularly in the amino acid sequence.
Exemplary antibodies and antigen-binding fragments that bind to CD47, having a full complement of three heavy chain and three light chain CDRs, are widely disclosed in the art. See, e.g., Lippincott (US 2019/0292258 A1); Zhao (CA 3089512 A1; cited in IDS); Pietsch (US 2018/0250395 A1; cited in IDS); Manning (AU 2016/324316 A1; cited in IDS); Sato (AU 2015/374301 A1; cited in IDS) and Swanson (US 2016/0257751 A1; cited in IDS).
Scope of species disclosed in original specification. The Examples disclose the preparation of anti-CD47 antibodies against a CD47 recombinant protein (e.g., Examples 1-2). Combinations of 30 VH and VL regions are presented in Table 2 (page 36), and individual antibody variable region sequences, heavy chain CDR sequences, and light chain CDR sequences are summarized in Tables 2-4 (pages 36-38).
Although the instant claims are drawn to “mixed and matched” combinations of VH regions and VL regions (with their corresponding CDRs), the disclosure only provides support for those combinations enumerated in Tables 3-5. By way of example, Applicant has support for anti-CD47 antibodies comprising a specific combination of heavy chain CDRs having the amino acid sequences of SEQ ID NO: 14, 17, and 23, respectively, or the amino acid sequences of SEQ ID NO: 15, 18, and 25, respectively (e.g., Table 4), in complement with selected combinations of light chain CDRs. Applicant does not have support for other combinations of the respective HCDR1, HCDR2, and HCDR3 sequences that are within the scope of the instant claims (e.g., the combination of SEQ ID NO: 16, 17, and 23, respectively, or the combination of SEQ ID NO: 15, 21, and 23, respectively). Applicant also has support for anti-CD47 antibodies comprising a specific combination of light chain CDRs having the amino acid sequences of SEQ ID NO: 30, 32, and 34, respectively, or SEQ ID NO: 31, 33, and 35, respectively (e.g., Table 5), in complement with selected combinations of heavy chain CDRs. Applicant does not have support for other combinations of the respective LCDR1, LCDR2, and LCDR3 sequences that are within the scope of the instant claims (e.g., the combination of SEQ ID NO: 30, 33, and 34, respectively).
Furthermore, Applicant has support for antibodies comprising a VH region having 100% sequence identity to one of SEQ ID NO: 11, 36-44, 50, and 56, in complement with a VL region having 100% sequence identity to one of SEQ ID NO: 12-13, 45-49, 51-55, or 65, specifically for the tested combinations that are set forth in Table 2 of the disclosure. By way of example, Applicant has support for a VH and VL pairing having the amino acid sequences of SEQ ID NO: 50 and 65, respectively, or a VH and VL pairing having the amino acid sequences of SEQ ID NO: 11 and 13, respectively. Applicant does not have support, for example, for a VH and VL pairing having the amino acid sequences of SEQ ID NO: 36 and 65, respectively, or for a pairing of the amino acid sequences of SEQ ID NO: 50 and 12, respectively.
MPEP § 2163 states that 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 absence of a representative number of species, the written description requirement for a claimed genus may be satisfied 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.
Although a number of species have been described, they cannot be considered representative because they are all highly structurally related, particularly in the CDRs of the antibody VH and VL domains utilized. As stated above, Applicant only has support for those specific embodiments which are specifically enumerated in the disclosure and which have been demonstrated by Applicant to possess the required functional activity of binding to CD47.
Conclusion. For all of the reasons presented above, one of skill in the art would not know which of the countless other anti-CD47 antibodies encompassed by the highly general structural requirements of the claims would also possess the required functional activity. Given the lack of shared structural properties that provide the claimed binding activity, the limited number of species described, and the fact that the species that were described cannot be considered representative of the broad genus, the Applicant did not possess the full genus of antibodies as broadly claimed at the time the application was filed.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lippincott (US 2019/0292258 A1).
Lippincott discloses anti-CD47 monoclonal antibodies (e.g., Abstract). An exemplary anti-CD47 antibody taught by Lippincott comprises a VH comprising the amino acid sequence of SEQ ID NO: 5, which has a VH CDR1 having two amino acid substitutions relative to instant SEQ ID NO: 14 (“SSYYWS”, including D30S and N31S relative to instant SEQ ID NO: 14) and a VH CDR2 having one amino acid substitution relative to instant SEQ ID NO: 17 (“YIYYSGNTNYNPSLKS”, including N56S relative to instant SEQ ID NO: 17) (e.g., ¶ 0029; page 14). See alignment of instant SEQ ID NO: 50 (“Qy”) relative to the amino acid sequence of SEQ ID NO: 5 disclosed by Lippincott (“Db”), below:
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253
618
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Claim 1-3, 6-7, and 11-15 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Grosveld (WO 2021/032174 A1; published February 25, 2021; earliest priority date: August 21, 2019; machine translation attached).
Grosveld discloses anti-CD47 antigen-binding proteins and applications thereof. Regarding claims 1-3 and 7, Grosveld discloses an anti-CD47 antibody having a VH comprising an amino acid sequence of SEQ ID NO: 81, which comprises the instantly claimed HCDR2 sequence of SEQ ID NO: 17 at positions 50-64 and shares 91.0% sequence identity to the instantly claimed VH comprising the amino acid sequence of SEQ ID NO: 50 (e.g., Summary of the invention; claim 22). See sequence alignment between instant SEQ ID NO: 50 (“Qy”) and the VH of SEQ ID NO: 81 as disclosed by Grosveld (“Db”) below:
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513
637
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Regarding claim 6, the sequence of SEQ ID NO: 81 above, at positions appearing to correspond to 81 and 82a according to Kabat numbering, comprises K and S at the respective residues.
Regarding claims 11-12, Grosveld discloses that the antibodies of the invention comprise an IgG4 constant region in which the S228P mutation (numbered according to EU numbering) was introduced to increase the stability of the antibody (e.g., Summary of the invention; Detailed description; Example 1).
Regarding claim 14, Grosveld provides nucleic acids encoding the antibody of the invention and vectors and host cells comprising the same (e.g., Detailed description). Regarding claims 13 and 15, Grosveld discloses pharmaceutical compositions comprising an anti-CD47 antibody of the invention and treatment of diseases such as solid tumors or hematological tumors (e.g., Detailed description).
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.
(1)
Claims 1-3 and 6-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of co-pending Application No. 18/035,591 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims anticipate the instantly claimed invention.
Regarding claims 1-2, co-pending claims 1, 4, and 6 recite a bispecific antibody comprising a variable region that specifically binds to CD47, comprising three VH CDRs having the amino acid sequences of SEQ ID NO: 21, 24, and 29, respectively (which share 100% sequence identity to instant SEQ ID NO: 14, 17, and 23, respectively). Regarding claims 3 and 6-7, co-pending claims 8 and 10-11 recite that the anti-CD47 variable region comprises a VH having the amino acid sequence of SEQ ID NO: 64 (which shares 100% sequence identity to instant SEQ ID NO: 50).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
(2)
Claims 2 and 11-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of co-pending Application No. 18/035,591 as applied to claims 1-3 and 6-7 above, further in view of Grosveld (WO 2021/032174 A1; supra).
The teachings of the co-pending reference application are recited in the provisional non-statutory double patenting rejection above. In addition, the co-pending claims recite a polynucleotide, expression vector, and host cell encoding the bispecific antibody of the invention; a pharmaceutical composition comprising the antibody or antigen-binding fragment of the invention; and a method for treating a disease in a patient that comprises administering said antibody (co-pending claims 18-20). Co-pending claims 18-20 depend from co-pending claim 1, which recites a bispecific antibody or antigen-binding fragment comprising a variable domain that specifically binds to PD-L1.
However, the co-pending reference application does not expressly teach a biomaterial (polynucleotide, expression vector, or host cell) or pharmaceutical composition comprising an antibody comprising an anti-CD47 binding domain, or a method of treating cancer or infection that comprises administering such an antibody. The co-pending claims also do not teach that the antibody is of an IgG4 isotype with a S228P substitution in the heavy chain.
The teachings of Grosveld are recited in the 35 U.S.C. § 102 rejection above.
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to (1) possess a biomaterial or pharmaceutical composition, as described by Grosveld, comprising an anti-CD47 antibody such as that taught in the co-pending claims; (2) to administer such an antibody in a method of treating cancer or infection; and (3) to modify said antibody to be of the IgG4 isotype with a S228P mutation. The skilled artisan would have been motivated to do so because Grosveld provides that antibodies with specificity for CD47 have utility in the treatment of solid or hematological tumors, and the biomaterials would allow for producing such an antibody, while the pharmaceutical composition could be administered in a method of treatment. Furthermore, antibodies with an IgG4 isotype, comprising the S228P substitution, have greater stability (as taught by Grosveld). There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that the antibodies recited in the co-pending claims and by Grosveld are functional equivalents each capable of binding specifically to CD47, and that one can substitute one for the other to achieve the same purpose.
This is a provisional nonstatutory double patenting rejection.
(3)
Claims 1-3, 6-7, 10, and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 34-46 of co-pending Application No. 18/681,485 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims anticipate the instantly claimed invention.
The co-pending reference application claims a method for treating an infectious disease or a tumor, comprising administering to a patient in need thereof an anti-PD-L1/CD47 antibody or antigen-binding fragment, wherein the anti-CD47 binding domain comprises the HCDR1 set forth in SEQ ID NO: 7, the HCDR2 set forth in SEQ ID NO: 8, and the HCDR3 set forth in SEQ ID NO: 9, which share 100% sequence identity to instant SEQ ID NO: 14, 17, and 23, respectively (co-pending claims 1 and 3), relevant to claims 1-2 and 15. Relevant to claims 3 and 6-7, co-pending claim 11 recites that the anti-CD47 binding domain comprises a VH comprising the amino acid sequence of SEQ ID NO: 11 (which shares 100% sequence identity to instant SEQ ID NO: 50).
Regarding claim 10, co-pending claim recites that the anti-CD47 heavy chain comprises an amino acid sequence having at least 80% or 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17 or 22. The instantly claimed heavy chain having the amino acid sequence of SEQ ID NO: 62 shares 98.6% sequence identity to SEQ ID NO: 17 and 98.9% sequence identity to SEQ ID NO: 22.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
(4)
Claims 2 and 11-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 34-46 of co-pending Application No. 18/681,485 (reference application) as applied to claims 1-3, 6-7, 10, and 15 above, further in view of Grosveld (WO 2021/032174 A1; supra).
The teachings of the co-pending reference application are recited in the provisional non-statutory double patenting rejection above.
However, the co-pending reference application does not expressly teach a biomaterial (polynucleotide, expression vector, or host cell) or pharmaceutical composition comprising the claimed antibody or antigen-binding fragment. The co-pending claims also do not teach that the antibody is of an IgG4 isotype with a S228P substitution in the heavy chain.
The teachings of Grosveld are recited in the 35 U.S.C. § 102 rejection above.
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to (1) possess a biomaterial or pharmaceutical composition, as described by Grosveld, comprising an anti-CD47 antibody such as that taught in the co-pending claims; and (2) to modify said antibody to be of the IgG4 isotype with a S228P mutation. The skilled artisan would have been motivated to do so because Grosveld provides that antibodies with specificity for CD47 have utility in the treatment of solid or hematological tumors, and the biomaterials would allow for producing such an antibody, while the pharmaceutical composition could be administered in the treatment method of the co-pending claims. Furthermore, antibodies with an IgG4 isotype, comprising the S228P substitution, have greater stability (as taught by Grosveld). There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that the antibodies recited in the co-pending claims and by Grosveld are functional equivalents each capable of binding specifically to CD47, and that one can substitute one for the other to achieve the same purpose.
This is a provisional nonstatutory double patenting rejection.
Allowable Subject Matter
Claims 5 and 9 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Citation of Pertinent Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Blein (WO 2015/063339 A1) discloses a method of producing heterodimeric bispecific antibodies in which the antibody product can be readily isolated after a single Protein A chromatography step with a high degree of purity, by modifying the VH region to comprise an amino acid substitution of 82aS (numbered according to Kabat numbering) (e.g., pages 4-8).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Elizabeth A Shupe whose telephone number is (703) 756-1420. The examiner can normally be reached Monday to Friday, 9:00am - 5:30pm EST.
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/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/Brad Duffy/Primary Examiner, Art Unit 1643