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 .
Election/Restrictions
Applicant’s election without traverse of claims 10-20 and 28-36 with species election of a heat shock protein in the reply filed on January 8, 2026 is acknowledged.
Status of Claims
Claims 1-46 are currently pending in the instant application. Claims 1-8, 21-26, and 37-46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Accordingly, claims 9-20 and 27-36 are under examination on the merits in the instant application.
Drawings
The drawings are objected to because Figure 4 contains sequence rule non-compliant subject matter. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. The objection to the drawings will not be held in abeyance.
Appropriate correction is required as instructed below.
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 amino acid sequences appearing in the drawings, see Figure 4, are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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.
Claim Rejections - 35 USC § 112
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 9 and 27 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 9 recites the limitation "the modification" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites the limitation "the modified cell line" in line 7. There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites “the target protein” in line 9. It is unclear whether “the target protein” is meant to refer to “a variant target protein” in line 4.
Claim 9 recites “(b) creating a cell-free antibody production system from the modified cell line”, wherein the subsequent steps (c), (d), and (e) also require use of the “cell-free antibody production system”. However, claim 9 is incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps pertain to how to create “a cell-free antibody production system” that is used in steps (c), (d), and (e), wherein the system is created “from the modified cell line”. That is, there is no step as to how “creating a cell-free antibody production system from the modified cell line” should be performed. As such, claimed steps (b), (c), (d), and (e) are incomplete, thereby rendering claim 9 and dependent claims thereof indefinite.
Claim 27 recites the limitation "the modification" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 27 recites the limitation "the modified mammalian cell line" in lines 7-8. There is insufficient antecedent basis for this limitation in the claim.
Claim 27 recites “the target protein” in line 10. It is unclear whether “the target protein” is meant to refer to “a variant target protein” in lines 4-5.
Claim 27 recites “(b) creating a cell-free antibody production system from the modified mammalian cell line”, wherein the subsequent steps (c), (d), and (e) also require use of the “cell-free antibody production system”. However, claim 27 is incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps pertain to how to create “a cell-free antibody production system” that is used in steps (c), (d), and (e), wherein the system is created “from the modified cell line”. That is, there is no step as to how “creating a cell-free antibody production system from the modified cell line” should be performed. As such, claimed steps (b), (c), (d), and (e) are incomplete, thereby rendering claim 27 and dependent claims thereof indefinite.
Claim Rejections - 35 USC § 112
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 9-20 and 27-36 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.
Regarding the claimed subject matter, the instant specification appears to at best describe an actual reduction to practice generating “R261Q single mutation cells and R261Q/H265Q double mutation cells”, which appear to be HEK293 cells expressing the aforementioned mutation(s) in GRP78, wherein the mutated HEK293 cells are transfected with the “fully human anti-GRP78 monoclonal antibodies (mAb) formatted as full-length IgG1 antibodies” identified as “B4” (comprising SEQ ID NOs:19-20) and “F6” (comprising SEQ ID NOs:23-24), wherein clonal cell populations that produce anti-GRP78 IgG antibodies binding to GRP78 expressed on the cell surface without binding to GRP78 expressed in the endoplasmic reticulum (ER) are selected for growing in suspension cultures. See paragraphs 0215 and 0217-0220. Hence, the antibody binding to applicant’s elected species, GRP78, is specific in not binding to the ER GRP78 while binding to the cell surface GRP78. The instant claims do not appear to reflect the disclosure of the specification. Most importantly, the specification does not disclose an actual production of “anti-GRP78 IgG antibodies” binding to only cell surface-expressed GRP78 using a cell-free system.
It is noted that the prior art submitted by applicant, see Sato et al. (US 2021/0054070 A1, applicant’s citation), does not teach making a cell-free (CF) system that produces an antibody, wherein the CF system is created “from” a modified cell line as required by the instant claims. Sato at best teaches producing a monoclonal antibody via a CF system comprising “an in vitro transcription and translation system” comprising using polynucleotides encoding a heavy chain and light chain of the monoclonal antibody, which has one or more amino acid substitutions relative to a parental antibody. See paragraphs 0006-0012, 0063-0064, 0125. In addition, Sato reports, “Unefficient assembly of the heavy and light chains of anti-CD47 antibody AB6.12 has been observed when co-expressed in the cell-free (CF) system” thus “heavy chain framework sequence” are modified “by engineering the 5 mutations and the 13 mutations on their HC sequences” for proper antibody production. See paragraphs 0227 and 0229. Hence, the actual production of a functional antibody comprising both the heavy chain and the light chain in a cell-free system was known to depend on variables/conditions that were deemed unpredictable.
Now, even if a cell-free system-based monoclonal antibody production method was deemed highly predictable as of the filing date sought in the instant case, the HEK293 cells comprising either R261Q mutation in GRP78 or R261Q and H265Q mutations in GRP78 transfected with two specific antibodies (“B4” and “F6”) comprising specific amino acid sequences are not a representative number of species within the claimed genus of “creating a cell-free antibody production system from the modified cell line”.
In view of the foregoing, if the claimed subject matter is interpreted in view of the aforementioned disclosure of the specification, it is concluded that the instant specification fails to adequately describe the entire genus in the manner to reasonably convey that the instant co-inventors had possession of the entire genus as of the filing date sought in the instant application, wherein it remains unknown whether the claimed method is meant to merely produce the prior art’s “B4” and “F6” antibodies in a cell-free system as it is unclear whether the “antibody to the target protein” is “B4” or “F6” is the limitation is ambiguously written as noted in the §112(b) rejection above.
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.
Claims 9-20 and 27-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-46 and 54-57 of copending Application No. 18/311,224.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the ‘224 claims drawn to a method that produces an anti-GPR78 antibody “in the culture supernatant” comprising using a “modified cell that is engineered to express a variant target protein that comprises a mutation of one or more amino acid residues of the target epitope”, wherein “the anti-GPR78 antibody is produced in the culture supernatant”, which is deemed cell-free. This rejection is established on the best possible interpretation of the instant claims, which are deemed indefinite for various reasons as set forth in the §112(b) rejection above.
Claims 9-20 and 27-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-17, and 19-47 of copending Application No. 18/311,235.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by and/or overlap in scope with the ‘235 claims drawn to a method that produces an antibody binding to a target protein including a heat shock protein comprising using a cell-free antibody production system. This rejection is established on the best possible interpretation of the instant claims, which are deemed indefinite for various reasons as set forth in the §112(b) rejection above.
Relevant Prior Art
The following prior art is considered pertinent to applicant's disclosure thus is made of record.
Note that the proper interpretation of the claimed subject matter is impossible as amply explained in the §112(b) rejection. In addition, applicant’s submission of two U.S. Patent application publications such as Sato et al. (US 2021/0054070 A1) and a foreign patent document in the IDS appears to be far from enlightening a person of ordinary skill in the art on the relevant prior art knowledge/techniques. The following prior art references appear to bear some relevance to the claimed subject matter.
1. Liu et al. (Clinical Cancer Research, 2013, 19:6802-6811) and Gill et al. (US 2018/0094054 A1) teach a monoclonal antibody (“Mab159”), which “specifically recognizes surface GRP78”. See page 6810 of Liu or paragraph 0151 of Gill. Hence, one of ordinary skill in the art could have synthesized a cell surface GRP78-binding monoclonal antibody in a cell-free system using a DNA encoding “Mab159” without the steps disclosed in the instant specification.
2. U.S. Patent Nos. 11,254,751 B2, 12,103,966 B2, 12,180,269 B2, and 12,577,301 B2 all disclose “Anti-GRP78 Monoclonal Antibodies” that “target an isogenic model of mammary cancer expressing cell surface GRP78”. See for instance column 18 of the ‘966 patent. In fact, all of the aforementioned patents appear to disclose “B4” and “F6” antibodies, which are disclosed in the instant specification for obtaining clonal modified cells. Hence, one of ordinary skill in the art could have synthesized a cell surface GRP78-binding monoclonal antibody in a cell-free system using a DNA encoding any one of the anti-GRP78 monoclonal antibodies (e.g., “B4” and “F6”) in the ‘751, ‘966, ‘269, and ‘301 patents without the steps disclosed in the instant specification.
3. Weidenbacher et al. (PNAS, 2019, 116:9947-9952) teach a cell-free “protect, modify, deprotect” (PMD) strategy for producing antibodies targeting a specific epitope, wherein the epitope of interest is protected with an mAb “to retain the epitope of interest”; the surface of the protein is modified; then the epitope is deprotected, wherein the PMD strategy “can selectively ablate binding of off-target Abs”. See pages 9948-9949.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
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