DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment filed on May 8, 2023 is acknowledged.
Claim 13 has been canceled.
Claims 1-12 are pending and currently under consideration.
3. 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.
4. 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.
5. Claims 1-12 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed.Cir.1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of the skilled in the art to practice the claimed invention.
The scope of the claims is drawn to a method for treatment of cancer in an individual in need thereof comprising administering a therapeutically effective amount of a conjugate comprising an antibody, a linker linked to the antibody via a covalent bond and a block copolymer which are linked to the linker via a covalent bond.
The specification discloses that the linker refers to a material that links an antibody for targeting cancer to a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymer, and exemplary linkers can be maleimide, succinic anhydrade and N-hydroxysuccinimide ester (e.g. see lines 5-10 in page 7). The specification further discloses working example of maleimide-pluronic F68/F127 conjugate and succinyl-PF68/PF127 conjugate (e.g. see Examples 1 and 2 in pages 16-20 of the instant specification as-filed)
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The claimed “linker” encompasses any linker without structure. The specification does not provide sufficient guidance and direction to enable for the all linkers encompassed by the claimed antibody conjugate.
It is known that linker plays a pivotal role in determining plasma stability and efficient payload release at the tumor site. For example, Lei et al. (ChemMedChem 2025, 20, e202500262 pages 1-22) teach that antibody-drug conjugate (ADC) comprises three core components: a monoclonal antibody specifically targeting tumor-associated antigens, a cytotoxic payload, and a chemical linker connecting them. (e.g. see right col. in page 2).
Lei et al. further teach some of the most frequent used conjugation such as common bioconjugation method with cysteine suffers instability causing the loss of the linker-payload from antibody (e.g. see left col. in page 11).
The instant claims are not limited to the linker with any specific structure but rather encompass any linker. There is insufficient objective evidence that the specific linkers disclosed in the specification, e.g. maleimide-pluronic F68/F127 conjugate and succinyl-PF68/PF127 conjugate, can be extrapolated to enable any or all linkers for the recited antibody conjugate to be administered for treatment of cancer.
In view of the lack of predictability of the art to which the invention pertains, method for treatment of cancer in an individual in need of by administering the recited antibody conjugate as well as the pharmaceutical composition comprising the antibody conjugate for the use in treating cancer would be unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue.
6. 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.
7. Claims 1-3, 6, 11, and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Song et al. (Biomaterials 2009, 1-11, reference on IDS) as evidenced by Shi (Molecular Imaging 2021, Article ID 3748315, pages 1-11).
Independent claim 1 is drawn to a method for treatment of cancer in an individual in need thereof comprising administering a therapeutically effective amount of a conjugate comprising an antibody, a linker linked to the antibody via a covalent bond and a block copolymer which are linked to the linker via a covalent bond.
Song et al. teach an anti-human hypoxia-inducible factor 1 alpha (HIF-1α) antibody conjugated pluronic triblock copolymers encapsulated with paclitaxel for cancer targeting therapy clinically (e.g. see Title and left col. in page 11).
Song et al. teach that the pluronic triblock copolymers are poly(ethylene glycol)-block-poly(propylene glycol)-block poly(ethylene glycol), PEO-block-PPO-block-PEO P123 (e.g. see abstract). Song et al. teach that the pluronic P123 is carboxyl-terminated and a carboxyl-terminated P123 is known to link to anti-HIF-1α antibody covalently by amide bond (e.g. see 2.2.3 in right col. in page 2 and 2.2.5 in the left col in page 3). Song et al. teach that the pluronic P123 was incubated with N-hydroxysuccinimide followed by covalently linked to human anti-HIF-1α antibody indicating succinate bridge which is a linker. Song et al. teach the antibody conjugate in 5% glucose solution or 0.9% NaCl and thus read on a pharmaceutical composition. Song et al. teach that the antibody conjugate encapsulated with paclitaxel can target specifically the human stomach cancer cells MGC803 and subsequently are internalized into cytoplasma via receptor-mediated endocytosis (e.g. see right col. in page 9).
As evidenced by Shi et al, human stomach cancer cell line MGC803 express EGFR (e.g. see 3.1 on the right col. in page 4). Further, Shi et al. teach EGFR is widely expressed in nearly every cancer type (e.g. see Discussion in page 6).
Therefore, the reference teachings anticipate the instant invention.
8. Claims 1-6, 11, and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ding et al. (Nanoscale 2011, 3:1813-1822, reference on IDS) as evidenced by Khaliq et al. (Pharmaceutics 2023, 15;2102:1-25) and Faller et al. (Biologics: Targets & Therapy, 2009, 3:419-428).
Ding et al. teach functional pluronic nanomicelles conjugated with anti-mesothelin antibody (e.g. see Title). Specifically, Ding et al. teach triblock polymer of F127COOH containing hydrophilic carboxylated poly(ethylene oxide) (PEO) and hydrophobic poly(propylene oxide)(PPO) unit generated by esterification with maleic anhydride (forming ester bond) and the new carboxylic acid groups act as the linker sites for covalently attaching anti-mesothelin antibody (e.g. see Fig. 1 and last paragraph in the left col. in page 1814). Ding et al. teach a pharmaceutical composition comprising the antibody conjugate in HPLC water (e.g. see 2n full paragraph in left col. in page 1815).
As evidenced by Khaliq et al., F-127 is poloxamer 407 (e.g. see first line of the last paragraph in page 3).
Ding et al. further teach in vivo tumor targeting by administering the anti-mesothelin antibody conjugate to treat mouse tumor model with pancreatic cancer cells (e.g. see 1st paragraph in left col. in page 1816).
As further evidenced by Faller et al., EGFR is commonly expressed in pancreatic cancer cells (e.g. see Abstract).
Therefore, the reference teachings anticipate the instant invention.
9. 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
10. Claims 1 and 7-10 are rejected under 35 U.S.C. 103 as being unpatentable over Ding et al. (Nanoscale 2011, 3:1813-1822, reference on IDS) in view of Park et al. (Biomaterials 2013, 1-9, reference on IDS).
The teachings of Ding et al. have been discussed above.
The reference teachings differ from the instant invention by not teaching a low molecular weight compound such as a chlorin photosensitizer chlorin e6.further binds to one end of the conjugate.
Park et al. teach conjugation of the photosensitizer chlorin e6 to pluronic F127 for enhanced cellular internalization of photodynamic therapy (e.g. see Title). Park et al. teach chlorin e6 (Ce6) is an effective photosensitizer given its several advantages for clinical use such as activation by near infrared wavelengths, relatively deep penetration through layers of tissues and potency against a broad spectrum of cancers (e.g. see right col. in page 1). Park et al. further teach pluronic F127 (PF127) was FDA approved copolymer that has been widely used as a pharmaceutical adjuvant. Park et al. teach that PF127 was employed to make a water soluble polymeric photosensitizer with enhanced cellular internalization and tumor-targeting efficacy via conjugation of Ce6. (e.g. see right col. in page 1). Park et al. teach FP127-Ce6 conjugate demonstrate enhanced cytotoxicity against mouse colon tumor CT-26 cells in vitro compared to free Ce6 (e.g. see Fig. 2b) and strongly suppressed CT-26 xenograft tumor growth after i.v. injection (e.g. see Fig. 5). Park et al. conclude that the PF127 Ce6 conjugate overcomes many of the problems associated with photosensitizers such as poor solubility, cellular internalization and tumor targeting efficiency.
It would thus be obvious to one of ordinary skill in the art at the time the instant invention was filed to combine the teachings of Ding et al. and Park et al. to produce an antibody conjugated to PF127-Ce6 to administered to treat cancer. An ordinary skill in the art would have been motivated to do so, and have a reasonable expectation of success, because Ding et al. teach anti-mesothelin antibody conjugated to PF127 via covalent ester bond and shows that the antibody conjugate is effective in reduce tumor sizes when administered to mouse model xenografted with human pancreatic cancer cells, and Park et al. teach that PF127 when conjugated with photosensitizer Ce6 shows enhanced cytotoxicity against mouse xenograft with colon cancer cells. As such, combining antibody-PF127 conjugate disclosed in Ding et al. with PF127-Ce6 conjugate would be expected to enhance cellular internalization and tumor targeting efficiency for the method for cancer treatment.
11. No claim is allowed.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
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, 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.
/CHUN W DAHLE/Primary Examiner, Art Unit 1641