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 .
DETAILED ACTIONPriority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1-16 have an effective filing date of 13 AUG 2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 1/22/2023, 3/27/2024, 8/13/2024, and 11/20/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restriction
In the response filed on 11/06/2025, Applicant elected without traverse:
Group I, claims 1-9, and 15-16
Species
Antibody or single-chain variable fragment thereof SEQ ID NO: 2
Cancer cell-penetrating peptide: SEQ ID NO: 89
Linker: GGGGS
Status of Claims
Claims 1-16 are currently pending and presented for examination on the merits.
Claims 5, 7, and 15 are amended.
Claims 8 and 10-14 are withdrawn by Examiner under 37 CFR 1.142(b) as being drawn to a non-elected invention.
Objection to the Claims
With respect to claim 6, this claim recites amino acid sequences that are at least four amino acids in length, and as such these sequences must be represented by a SEQ ID NO. For example, GGGGS could be represented as amino acids 118-122 of SEQ ID NO: 2.
With respect to claim 8, this claim recites amino acid sequences that are at least four amino acids in length, and as such these sequences must be represented by a SEQ ID NO. For example, CGGGGG could be represented as amino acids 231-236 of SEQ ID NO: 83.
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 1-7, 9, and 15-16 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.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “in which” in claim 1 is used by the claim to mean “comprising,” while the accepted meaning is “having.” The term is indefinite because the specification does not clearly redefine the term. Applicant is encouraged to use “comprising” or “consisting of” language instead of “in which.”
Transitional phrases such as "having" must be interpreted in light of the specification to determine whether open or closed claim language is intended. See, e.g., Lampi Corp. v. American Power Products Inc., 228 F.3d 1365, 1376, 56 USPQ2d 1445, 1453 (Fed. Cir. 2000) (interpreting the term "having" as open terminology, allowing the inclusion of other components in addition to those recited); Crystal Semiconductor Corp. v. TriTech Microelectronics Int’l Inc., 246 F.3d 1336, 1348, 57 USPQ2d 1953, 1959 (Fed. Cir. 2001) (term "having" in transitional phrase "does not create a presumption that the body of the claim is open"); Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1573, 43 USPQ2d 1398, 1410 (Fed. Cir. 1997) (in the context of a cDNA having a sequence coding for human PI, the term "having" still permitted inclusion of other moieties). The transitional phrase "composed of" has been interpreted in the same manner as either "consisting of" or "consisting essentially of," depending on the facts of the particular case. See AFG Industries, Inc. v. Cardinal IG Company, 239 F.3d 1239, 1245, 57 USPQ2d 1776, 1780-81 (Fed. Cir. 2001) (based on specification and other evidence, "composed of" interpreted in same manner as "consisting essentially of"); In re Bertsch, 132 F.2d 1014, 1019-20, 56 USPQ 379, 384 (CCPA 1942) ("Composed of" interpreted in same manner as "consisting of"; however, the court further remarked that "the words ‘composed of’ may under certain circumstances be given, in patent law, a broader meaning than ‘consisting of.’").
With respect to claim 9, the phrase “represented by” renders the claim indefinite, because one skilled in the art has no means of determining which amino acid sequences are “representative” of those recited in the claim. As such one skilled in the art would be unable to readily delineate the metes and bounds of the claim.
Claims 15 and 16 are rejected under 35 U.S.C. 112(b), because the claims are “use” claims. According to MPEP 2173.05(q), “[a]ttempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: ‘[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon’ was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986).” Claim 15 recites a pharmaceutical composition for use in tumor treatment; however the claim does not recite any active, positive steps defining how this use is actually practiced and is therefore rejected under 35 U.S.C. 112(b).
Claim Rejections - 35 U.S.C. 102(a)(1)
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.
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.
Claim(s) 1 and 2 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lim et al (A Cancer Specific Cell-Penetrating Peptide, BR2, for the Efficient Delivery of an scFv into Cancer Cells, PLoS ONE 8(6): e66084, 2013, IDS 1/22/2023).
In regards to claim 1, Lim et al teaches a cell-penetrating peptide (CPP) [Abstract]. Lim et al further teaches CPP as a cancer treatment [Abstract]. Lim et al further teaches the CPP has cancer cell specificity [Abstract]. Lim et al further teaches BR2 has cancer specificity, but is without toxicity to normal cells [Abstract]. Lim et al further teaches BR2 as a cancer-specific drug carrier was demonstrated by fusion of BR2 to a single-chain variable fragment (scFv) directed toward a mutated K-ras [Abstract]. Lim et al further teaches cell-penetrating peptide BR2 has great potential as a useful drug delivery carrier with cancer cell specificity [Abstract].
In regards to claim 2, Lim et al teaches a single-chain variable fragment (scFv) directed toward a mutated K-ras [Abstract].
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.
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.
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 nonobviousness.
Claims 1-2, 4-5, and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Lim et al (A Cancer Specific Cell-Penetrating Peptide, BR2, for the Efficient Delivery of an scFv into Cancer Cells, PLoS ONE 8(6): e66084, 2013, IDS 1/22/2023), and further in view of Park et al (US 9849190 B2).
In regards to claim 1, Lim et al teaches a cell-penetrating peptide (CPP) [Abstract]. Lim et al further teaches CPP as a cancer treatment [Abstract]. Lim et al further teaches the CPP has cancer cell specificity [Abstract]. Lim et al further teaches BR2 has cancer specificity, but is without toxicity to normal cells [Abstract]. Lim et al further teaches BR2 as a cancer-specific drug carrier was demonstrated by fusion of BR2 to a single-chain variable fragment (scFv) directed toward a mutated K-ras [Abstract]. Lim et al further teaches cell-penetrating peptide BR2 has great potential as a useful drug delivery carrier with cancer cell specificity [Abstract].
In regards to claim 2, Lim et al teaches a single-chain variable fragment (scFv) directed toward a mutated K-ras [Abstract].
Lim et al does not specifically teach cancer cell-penetrating peptide consisting of SEQ ID NO: 89. However, this deficiency is made up in the teachings of Park et al.
In regards to claim 4, Park et al teaches a cell-penetrating peptide comprising SEQ ID NO: 6. Park et al further teaches the peptide can selectively penetrate tumor cells [0002]. A comparison of instant SEQ ID NO: 89 and SEQ ID NO: 6 of Park et al is shown below.
Instant SEQ ID NO: 89 and SEQ ID NO: 6 of Park et al.
Matches 15; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GKCSTRGRKCCRRKK 15
|||||||||||||||
Db 1 GKCSTRGRKCCRRKK 15
One of ordinary skill, before the effective filing date, would have been motivated to combine Lim’s method of use a single chain variable fragment (scFv) to target a cancer cell and further penetrate the cancer cell with the scFv, with Park’s method of using cell-penetrating peptide comprising SEQ ID NO: 89 to penetrate the cell. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Lim and Park’s methods for a scFv that targets a cancer cell by the oncogenic mutant protein, penetrates the cancer cell, and enters, because Lim teaches a peptide that targets a tumor cell’s surface antigen and penetrates the cell, and Park teaches penetrating cells using SEQ ID NO: 6.
In regards to claim 5, Park et al teaches the cell-penetrating peptide is attached by S-S bond at the N-terminus to other proteins, see claim 1.
In regards to claims 15-16, Lim et al teaches using cell-penetrating peptides for cancer treatment [Abstract]. Lim et al further teaches treating colon carcinoma tumor cells [Left column, 3rd Paragraph, pg. 10].
Claims 1-2, 4-6, and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Lim et al (A Cancer Specific Cell-Penetrating Peptide, BR2, for the Efficient Delivery of an scFv into Cancer Cells, PLoS ONE 8(6): e66084, 2013, IDS 1/22/2023), Park et al (US 9849190 B2) as applied to claims 1-2, 4-5, and 15-16 above, and further in view of Kim et al (US 20190144566 A1).
The teachings of Lim et al and Park et al are discussed above.
Lim et al does not specifically teach using the linker GGGGS. However, this deficiency is made up in the teachings of Kim et al.
In regards to claim 6. Kim et al teaches the use of a cytosol penetrating antibody [Abstract]. Kim et al further teaches numerous cell-penetrating antibodies using linkers comprising GGGGS [0333, 0426, & 0468]. Kim et al further teaches targeting KRAS mutations [0183].
One of ordinary skill, before the effective filing date, would have been motivated to combine Lim’s method of use a single chain variable fragment (scFv) to target a cancer cell and further penetrate the cancer cell with the scFv, with Park’s method of using cell-penetrating peptide comprising SEQ ID NO: 89 to penetrate the cell, with Kim’s method of using a linker on antibodies comprising GGGGS. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Lim and Park’s methods for a scFv that targets a cancer cell by the oncogenic mutant protein, penetrates the cancer cell, and enters, because Kim teaches the linker peptide may mediate the fusion with the bioactive molecules at various locations of an antibody.
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 1, 5, and 15-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 9849190 ('190). Although the claims at issue are not identical, they are not patentably distinct from each other because:
With respect to claim 1, is not patentably distinct from claim 1 of ‘190. Specifically, a peptide having cancer selective translocation function, binds specifically to vascular endothelial growth factor (VEGF) in tumor cells, and is linked to peptide having the translocation function. Furthermore, ‘190 Figure 1A and 1B teach the tumor cell-penetrating abilities of a VEGF-binding protein transduction domain (VPTD) peptide [Figures 1A and 1B].
With respect to claim 5, is not patentably distinct from claim 1 of ‘190. Specifically, the peptide having translocation function linked to N-terminus or C-terminus of oncogenic protein VEGF.
With respect to claims 15-16, is not patentably distinct from claim 1 of ‘190. Specifically, a protein for treating breast cancer.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS JOHN SULLIVAN whose telephone number is (571)272-0509. The examiner can normally be reached Mon - Fri: 7:30AM - 4:30PM.
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, Samira Jean-Louis can be reached at (571) 270-3503. 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.
/DENNIS J SULLIVAN/Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642