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 .
Applicant’s amendment, filed on 11/25/2025, is acknowledged.
Claims 11-25, 32, 37, 38, and 41 are cancelled.
Claims 1-10, 26-31, 33-36, 39, and 40 are currently pending.
Election/Restrictions
Applicants’ election with traverse of Group I, claims 1-9, directed to an anti-CD22 sdAb, filed on 11/25/2025, is acknowledged. The traversal is on the grounds that claims 10, 27, 29, and 34 have been amended to include all limitations of instant claim 1 (Remarks pg. 10). This is not found persuasive because for the reasons stated in the Restriction Requirement mailed on 10/01/2025, the different compositions of Groups I-VIII do not have share common core structure and therefore do not have Unity of Invention.
The requirement is still deemed proper and is therefore made FINAL.
Applicants’ election without traverse of the anti-CD22 sdAb comprising CDR1-3 of SEQ ID NO: 139, 8, and 9 respectively. SEQ ID NO: 70 reads on the elected CDRs.
Claim 33 has been amended and no longer recites the invention of Group I.
Additionally, claims 34, 39, and 40 have been amended an no longer recites a method of treatment comprising administration of the sdAb of Group I. Claims 34, 39, and 40 now only recite a method of treatment comprising administration of a pharmaceutical composition comprising an engineered immune cell comprising an anti-CD22 CAR (i.e., the invention of Group VI).
As stated in the Restriction Requirement mailed on 10/01/2025, the inventions of Groups I and V have Unity of Invention. The instant claims no longer recite the invention of Group V.
Claims 10, 26-31, 33-36, 39, and 40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions.
Claims 1-9 are under examination as reading on anti-CD22 sdAb comprising CDR1-3 of SEQ ID NO: 139, 8, and 9 respectively, and a VHH of SEQ ID NO: 70.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 7/08/2025, 8/29/2024, 5/29/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner in their entireties.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Specifically, the instant specification discloses multiple amino acid sequences without the corresponding sequence identifiers in ¶[00320], [00331],
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The use of the terms:
Lenti-X™ (¶[00466]);
Attune™ NXT (¶[00467]);
Dynabeads™ (¶[00473]);
MACSibead™ (¶[00392], [00481]);
ONE-Glo™ (¶[00486], [00506]); and
MabSelect SuRe™ (¶[00497])
which are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 6-9 are objected to because each of the claims recite “…wherein anti-CD22 sdAb…” and should most likely recite “wherein the anti-CD22 sdAb” to correct minor typographical errors.
Claim Rejections - 35 USC § 112
Claims 1-9 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush groupings of claims 1 and 2 are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The Markush groupings of claims 1 and 2 contain structurally different single domain antibody clones. For example, the elected VHH species of SEQ ID NO: 70 (claim 2(ii)) only shares approximately 30% sequence identity with SEQ ID NO: 69 (claim 2(i)):
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Additionally, Applicant is advised that the Office limits up to 25 ABSS query sequences search per application, the instant application comprises unreasonable number of sequences to be searched. Each single domain antibody comprises 3 CDR sequences and a VHH. The instant application is claiming at least 95 amino acid sequences. The Office limits the search up to 25 SEQ ID Nos per request.
Dependent claims 3-9 do not resolve this issue and are also rejected on the basis of an improper Markush grouping.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use, and limit the claims to up to 25 SEQ ID NOs to be searched.
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.
Claim 3 is 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 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 inventors, at the time the application was filed, had possession of the claimed invention.
Claim 3 is dependent on claim two. Claim 2 recites (regarding the elected species of sdAb only): “(ii) a CDR1, a CDR2, and a CDR3 having the amino acid sequences of the CDR1, CDR2, and CDR3, respectively, as set forth in SEQ ID NO: 70;”
Claim 3 recites “wherein the CDR1, CDR2, or CDR3 are determined according to the Kabat numbering scheme, the IMGT numbering scheme, the AbM numbering scheme, the Chothia numbering scheme, the Contact numbering scheme, or a combination thereof.”
Thus, claim 3 encompasses a genus of anti-CD22 sdAbs that comprise the CDR1-3 of the VHH sequences recited in claim 2, wherein the CDRs can be from any of the recited numbering schemes, including a mix of two or even three CDRs from different numbering schemes.
However, the specification fails to provide adequate written description support for a such genus of single domain antibodies encompassing combinations of CDRs from any of the recited numbering schemes.
The claims are not supported by a description that satisfies 35 U.S.C. § 112(a) or 35 U.S.C. § 112, first paragraph. "[T]he test for sufficiency [of the written description] is whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad Phanns., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en bane).
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." Id. at 1350. "[A]n adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials." Id.
"[F]unctional claim language can meet the written description requirement when the art has established a correlation between structure and function." Id. "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 that one has invented a genus and not just a species." Id.
"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" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
The specification discloses identification of anti-CD22 VHH clones from camels immunized with CD22, followed by screening for sdAb clones that specifically bind (Example 1). Table 2 discloses specific anti-CD22 VHH antibody clone structures identified from the screen (Table 2). The specification further discloses ([00476]): “[t]he CDR (e.g., as defined by Kabat or IMGT numbering scheme) and VHH sequences are summarized in Table 2 and the Sequence Listing provided herein.” The specification does not disclose mixing and matching CDRs from different numbering schemes to generate functional anti-CD22 sdAbs.
With respect to representative number of species, see AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014). Also, see MPEP 2163 Il(A)(3)(a))(ii):
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. 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. See Abb Vie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.").
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
While the instant specification discloses single domain antibody structures that bind to CD22 that all have CDRs from the same numbering scheme (for example, all from Kabat), no representative species of sdAbs were given that mixed and matched CDRs from different numbering systems.
Moreover, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed antigen binding constructs to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). The Court reiterated that adequate written description must “contain enough information about the actual makeup of the claimed products . . . .” The Court simultaneously suggested that the “newly characterized antigen” test “flouts” section 112 because it “allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen.” The Court concluded that for written description of an antibody to be adequate when presented with “functional” terminology, there must be an established correlation in the art between structure and function.
Given the broadly claimed class of sdAbs, and in the absence of sufficient disclosure of relevant identifying characteristics for the broadly claimed class of antigen binding molecules that bind to a ligand, the patentee must establish “a reasonable structure-function correlation” either within the specification or by reference to the knowledge of one skilled in the art with functional claims. AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014), MPEP 2163.
Neither the instant specification nor the prior art support mixing and matching CDRs from different numbering schemes to generate functional anti-CD22 sdAb structures. Both the specification and the prior art support having all three CDRs from an sdAb clone from the same numbering system to generate functional anti-CD22 sdAb structures.
For example, Dondelinger et al. (Front Immunol. 2018 Oct 16;9:2278. doi: 10.3389/fimmu.2018.02278) teaches advantages and disadvantages of the different antibody numbering schemes, including Kabat (pg. 3), Chothia (pg. 3-4), Martin (pg. 4-5), Gelfand (pg. 5), IMGT (pg. 5-6), and Honneger’s (pg. 6-7). However, Dondelinger et al. does not teach mixing and matching CDRs from these different numbering scheme to generate a function antibody.
Possession is not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Sufficient description to show possession of such a genus may be achieved by means of a recitation of a representative number of sdAbs or binding fragments thereof falling within the scope of the genus or of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. See Eli Lilly, 119F.3d at 1568, 43 USPQ2d at 1406.
Claim 3 does not meet the requirements of 35 U.S.C. 112(a) for written description.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the written description inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed.
To overcome this rejection, it is recommended to amend claim 3 to remove the phrase “or a combination thereof”.
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.
Claim 6 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 6 is indefinite because 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 6 recites the broad sequence identity “at least 75%”, followed by the narrower ranges “at least 80%”, “at least 85%”, “at least 90%”,“at least 95%”, “at least 96%”, “at least 97%”, “at least 98%”, and “at least 99%”. It is recommended to amend the claim to one sequence identity value to overcome this rejection.
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.
Claim 1-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 12-17, 21, 29, 33-39, 40, 44, and 49 of copending Application No. 18/015,505 (App ‘505), as evidenced by Wilken et al. (Int Rev Immunol. 2018 Jan 2;37(1):69-76. doi: 10.1080/08830185.2017.1397657. Epub 2017 Nov 28). Although the claims at issue are not identical, they are not patentably distinct from each other.
App ‘505 claims compositions comprising single-domain antibodies comprising the VHH sequence of SEQ ID NO: 130 (claims 1 and 21), which is 100% identical to instant SEQ ID NO: 70 (i.e., the limitations of instant claims 1-6):
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It would have been obvious to one with ordinary skill in the art to have modified the invention claimed by App ‘505 to make anti-CD22 single-domain antibodies comprising the VHH sequence of instant SEQ ID NO: 70, as this single domain antibody is claimed by App ‘505. One would have been motivated to make this change to generate anti-CD22 single domain antibodies which could be used as a therapeutic or CD22 expression diagnostic.
Regarding claim 7, Wilken et al. is provided as an evidentiary reference to demonstrate that single-domain antibody VHH fragments are camelid antibodies (Abstract): “[c]amelid heavy-chain variable domains (VHHs) are the smallest, intact, antigen binding units to occur in nature”, meeting the claim limitations.
Therefore, the invention encompassed by the instant application is a prima facie obvious variant of the invention claimed by App ‘505, as evidenced by Wilken et al. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 8 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 12-17, 21, 29, 33-39, 40, 44, and 49 of copending Application No. 18/015,505 (App ‘505, supra), as evidenced by Wilken et al. (supra), as applied to claims 1-7 above, and further in view of Vincke et al. (J Biol Chem. 2009 Jan 30;284(5):3273-3284. doi: 10.1074/jbc.M806889200. Epub 2008 Nov 14).
The invention encompassed by App ‘505, as evidenced by Wilken et al., has been discussed supra. App ‘505 as evidenced by Wilken et al. does not teach humanized sdAbs (i.e., the limitations of instant claim 8).
Vincke et al., in the same field of endeavor, teaches a general method of humanization of camelid VHH sdAbs (Fig. 7):
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Vincke et al. teaches methods of such as humanization technique (“Experimental Procedures”), and demonstrated the technique could be used to humanize two different sdAbs, NbHuL6 and NbBcII10 (pg. 3277-3299). Vincke et al. further teaches that humanization is typically required before an antibody can be accepted as a human therapeutic (Introduction). Additionally, Vincke et al. teaches (Introduction): “…a general strategy is proposed to generate a humanized version of any Nanobody with maximal retention of stability and antigen-binding characteristics. Finally, a universal humanized Nanobody scaffold was identified that accommodates antigen-binding loops from Nanobodies, even those from other subfamilies or species.”
It would have been obvious to one with ordinary skill in the art to have modified the invention claimed by App ‘505, as evidenced by Wilken et al., in view of Vincke et al. to humanize the anti-CD22 sdAb claimed by App ‘505 with a reasonable expectation of success, as Vincke et al. teaches a universal humanization method that can be applied to any sdAb. One would have been motivated to make this change to humanize the camelid antibody claimed by App ‘505 to reduce its immunogenicity in humans and make the sdAb a more acceptable therapeutic to be used in humans.
Therefore, the invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘505 as evidenced by Wilken et al., in view of Vincke et al. This is a provisional nonstatutory double patenting rejection.
Claim 9 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 12-17, 21, 29, 33-39, 40, 44, and 49 of copending Application No. 18/015,505 (App ‘505, supra), as evidenced by Wilken et al. (supra), as applied to claims 1-7 above, and further in view of Oliveira et al. (J Control Release. 2013 Dec 28;172(3):607-17. doi: 10.1016/j.jconrel.2013.08.298).
The invention encompassed by App ‘505, as evidenced by Wilken et al., has been discussed supra. App ‘505 further claims methods of treatment comprising administration of compositions comprising the sdAb (claim 39), including CD22 associated disorders (claim 40), and cancer (claim 41).
App ‘505 as evidenced by Wilken et al. does not teach conjugates comprising the sdAb chemically fused or genetically conjugated to an agent (i.e., the limitations of instant claim 9).
Oliveira et al., in the same field of endeavor, teaches advantages to sdAbs (pg. 609): “…nanobodies could refold and bind to their targets even after a long incubation period at 80-92 °C… molecular manipulations for generating multivalent or multispecific single-chain antibodies are relatively easy… nanobodies are very promising building blocks to function as novel antibody molecules for a wide variety of applications.” Oliveira et al. further teaches (Section 3.2): “[a]nother possibility to further increase the therapeutic efficacy of nanobodies would be to use nanobodies as a mean to specifically deliver a certain effector domain (e.g. enzyme or toxin) to or into the target cell… site-directed conjugation to a C-terminal cysteine would control where the effector domain binds to the nanobody, minimizing the chances of interfering with nanobodies' binding properties… the nanobody should assure specific targeting, accumulation, and retention of the conjugate at the tumor (possibly through internalization of
the conjugates). Ideally, the effector domain would be very potent, leading to cell death and complete tumor regression, rather than only inhibiting tumor cell proliferation. Also, at the same time, the conjugates would be safe to normal tissues and only be toxic at the targeted regions (i.e. cancer cells).”
It would have been obvious to one with ordinary skill in the art to have modified the invention claimed by App ‘505, as evidenced by Wilken et al., in view of Oliveira et al. to use the sdAb claimed by App ‘505 as a conjugate with a toxin, as Oliveira et al. teaches methods of making sdAb conjugates comprising the nanobody with a toxin site-directed to conjugate to the C-terminal cysteine. One would have been motivated to make this change to use the sdAb claimed by App ‘505 as a therapeutic conjugate to treat CD22 associated diseases such as cancer.
Therefore, the invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘505 as evidenced by Wilken et al., in view of Oliveira et al. This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEC JON PETERS whose telephone number is (703)756-5794. The examiner can normally be reached Monday-Friday 8:30am - 6:00pm EST.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALEC JON PETERS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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