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 .
Priority
The current application claims priority to U.S. provisional application no. 63/487408, filed on 28 February 2023. The effective filing date is 28 February 2023.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 25 November 2024 was considered by the examiner.
Status of Application, Amendments, and/or Claims
Claims 1-56 are the original claims. In the preliminary amendment of 05 June 2024, claims 19-22 and 37-47 were cancelled, claims 3-8, 11, 14-16, 23-29, and 31-36 were amended, and claims 48-56 were added. Claims 1-18, 23-36, and 48-56 are pending and the subject of this office action.
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.
Claims 1-4, 5-6, 7-13, 14, 15, 16-18, 24-25, 26-27, 28-30, 31, 32, 33, 34, 35, 36, 48-49, and 50-56 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO2022074628 A1 (herein Sidhu).
In regard to claims 1-3, Sidhu relates to synthetic multivalent binding molecules that bind to the spike protein of SARS-CoV-2 and compete with receptor binding to inhibit viral infection (Abstract). The molecules disclosed by are Sidhu are taught to “exploit the modular nature of antibodies and antibody-derived molecules to generate multivalent antibody formats with enhanced potency against the SARS-CoV-2 virus” ([0007]). The authors define "antibody" to include human antibodies, humanized antibodies, monoclonal antibodies, polyclonal antibodies, antibody binding fragments, single chain and other chimeric antibodies (Relevant to instant claim 14) ([0080]). The term “format”, as referenced above, is defined as referring to multivalent binding molecules, which may include neutralizing antibodies (Relevant to instant claim 15) ([0095]). SPIKE. The authors disclose multiple multivalent binding molecule formats that teach the limitations established in various claims of the current application, in which Fc domains are used as multimerization moieties (Figure 5). It is also taught that the Fc domain may be comprised of IgG domains, such as IgG1 or IgG subclasses (Relevant to instant claims 16-18) ([0080]).
Format 44 of Figure 5, shown below, teaches the limitations of instant claims 1 and 2 (4 anti-spike antigen binding domains operably linked by a Fc multimerization domains). Additionally, it teaches the limitations of instant claims 24 and 25, as the antigen binding domains are all Fabs.
PNG
media_image1.png
200
400
media_image1.png
Greyscale
This figure and the accompanying description are silent regarding the nature of the intermolecular disulfide bond (depicted as a grey sphere), which is shown to be in the linkage between CH1 and CH2 regions. Sequence 74 of the application (Page 182) provides an amino acid sequence embodying this format, as well as the nucleic acid encoding said amino acid sequence (Relevant to instant claim 31). The sequence comprising the Fc domains comprises an IgG1 hinge region, which links the CH1 region of an anti-spike Fab to the CH2 region of the Fc domain, as shown below.
DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASDLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGSYLFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFDLTGSYMHWVRQAPGKGLEWVAGISASGGATAYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSRSSSYSSSGWRYYSGAFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
VL-CL
Linker
VH-CH1
Hinge
Fc Domain
In regard to claim 4, format 41 of figure 5 discloses a multivalent anti-spike protein binding molecule, that teaches the limitations of instant claim 4, as shown below.
PNG
media_image2.png
200
400
media_image2.png
Greyscale
In regard to claims 5 and 6, Sidhu teaches an embodiment, in which the multivalent anti-spike protein binding molecule comprises two polypeptide monomers, each comprising an Fc region, that dimerizes via the intrinsic properties of the Fc region. It is also taught that the resulting dimer may be homodimeric or heterodimeric (via the knob-in-holes configuration) ([0018]).
In regard to claims 7-9, 11, and 12, Sidhu discloses a format (format 44 figure 5), that teaches the limitations of instant claim 3, discussed above. The amino acid sequence of an example embodiment of this format, sequence 74 (Page 182), is a monospecific multivalent anti-spike protein binding molecule, and by its nature satisfies the limitations, regarding antigen binding domain configuration, established in instant claims 7-9, 11, and 12.
In regard to claims 50-52, 54, and 55, Sidhu discloses a format (format 41 figure 5), that teaches the limitations of instant claim 4, discussed above. The amino acid sequence of an example embodiment of this format, sequence 68 (Page 170), is a monospecific multivalent anti-spike protein binding molecule, and by its nature satisfies the limitations, regarding antigen binding domain configuration, established in instant claims 50-52, 54, and 55.
In regard to claims 28-30, Sidhu teaches that the disclosed multivalent anti-spike protein binding molecule may be either monospecific or multispecific, wherein not all binding sites bind the same epitope ([0020]).
In regard to claim 27 and 28, format 21 of figure 5, shown below, teaches a multivalent anti-spike protein binding molecule comprising four scFvs, which teaches the limitations of claims 17 and 18.
PNG
media_image3.png
200
400
media_image3.png
Greyscale
In regard to claim 32, Sidhu teaches an embodiment including a recombinant cell producing a multivalent binding molecule, as described for 35 U.S.C. 102(a)(1) rejection of claim 1 ([0042]).
In regard to claim 33, Sidhu teaches a method for producing a multivalent binding molecule, as described for 35 U.S.C. 102(a)(1) rejection of claim 1 ([0045])
In regard to claim 34, Sidhu teaches a pharmaceutical composition, comprising a multivalent binding molecule, as described for 35 U.S.C. 102(a)(1) rejection of claim 1, as well as an acceptable carrier, diluent or excipient ([0169]).
In regard to claims 35 and 36, Sidhu teaches a method for inhibiting a coronavirus infection of a cell having a receptor for the coronovirus by contacting the cell with an effective amount of a multivalent binding molecule that targets the coronavirus ([0037]). It is also taught that the abovementioned receptor may be ACE2. It is additionally, taught that the method may be used for the treatment of a subject infected with a coronavirus ([0039]).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
Claims 10, 13, 53, and 56, are rejected under 35 U.S.C. 103 as being unpatentable over WO2022074628 A1 (herein Sidhu).
Sidhu teaches a multivalent anti-spike protein binding molecules that embody the limitations established in instant claims 3 and 4, see 35 U.S.C. 102(a)(1) rejections of claims 3 and 4. Additionally, Sidhu teaches that these molecules may be either monospecific or multispecific/bispecific ([0020]). The limitations established in claims 10, 13, 53, and 56 reference the configuration of the antigen binding domains in a bi-specific tetravalent anti-spike protein binding molecule (2 pairs of Fab moieties each targeting a different epitope). The differences in these configurations result in multivalent molecules with Fab arms that comprise either two identical Fab moieties or two distinct Fab moieties. Based on the examiner’s understanding of the results presented for examples 1-3 of the specification, it is not apparent that the applicant tested configurations, in which the Fab arms comprised mixed Fab moieties, and as such there is no evidence that such a configuration would possess different properties from a configuration, in which the Fab arms comprised identical Fab moieties. In this scenario, the selection of either configuration would have been a matter of design choice, as both configurations possess 2 pairs of Fab moieties each targeting a different epitope.
Double Patenting
The non-statutory 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 non-statutory 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 non-statutory 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 non-statutory 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, 14, 16, 23-25, 28-36 are provisionally rejected on the grounds of non-statutory double patenting as being unpatentable over claims 1-14, and 34-40 of co-pending Application No. 18/589364 (herein ‘364). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 of ‘364 references “a multivalent anti-spike protein binding molecule comprising at least 5 anti-spike protein antigen-binding domains (ABD) operably linked by one or more multimerization moieties”. Claim 1 of the current application, which states “a multivalent anti-spike protein binding molecule comprising at least 4 anti-spike protein antigen-binding domains (ABD) operably linked by one or more multimerization moieties”. These claims encompass overlapping molecules, as the upper limit of ABDs is undefined in both claims, as a result any multivalent molecule, as defined in both claims, which comprises 5 or more ABDs would be encompassed by both claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 23 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 12496470 (herein ‘470) in view of WO2022074628 A1 (herein Sidhu).
Claim 1 of ‘470 references an antibody or antigen binding fragment thereof that specifically binds to a CoV-S, wherein the antibody or antigen-binding fragment comprises various sets of heavy and light chain CDRs. One set, SEQ ID Nos: 552, 554, 556, 84, EVS, and 560, share 100% sequence identity with those established in instant claim 23. This claim, as well as the additionally cited dependent claims, encompass the multivalent anti-spike protein binding molecule, referenced in instant claims 23, as this molecule is comprised of the CDR claimed in claim 1 of ‘470. Furthermore, the use of this antigen binding fragment in a multivalent anti-spike protein binding molecule, as taught Sidhu, would have been obvious, as claim 2 ‘470 teaches that the claimed antibodies possess characteristics (high affinity toward CoV-S, in vivo efficacy), which align with the requirements established in claim 1 of Sidhu, regarding the nature of the antigen binding fragment (e.g. the binding fragment must bind a coronavirus peptide), within said multivalent anti-spike protein binding molecule.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATTHEW CURRAN METCALF whose telephone number is (571)272-5520. The examiner can normally be reached 7:30AM-5:00PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at (571)272-2911. 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.
/MATTHEW CURRAN METCALF/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
Prosecution Insights