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 March 31, 2026 is acknowledged.
Claims 4-6 and 13 have been canceled.
Claims 1-3 and 7-12 are pending and currently under consideration.
3. In view of applicant’s amendment, following rejections are set forth.
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 1-3 and 7-12 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 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.
This is a Written Description, New Matter rejection.
The newly added limitations “a linker linked to the antibody via -S- bond or an amide bond and “wherein the block copolymer is covalently linked to the linker, and PPO has a repeating unit number of 20 to 80” are not supported by the original disclosure or claim as filed.
Applicant’s amendment, filed on March 31, 2026, directs to support to “throughout the specification”.
However, the specification as filed does not provide sufficient written description of the above-mentioned “limitations”. The specification does not provide sufficient support for PPO having a repeating unit number of 20 to 80 and linked to the antibody via -S- bond or an amide bond.
The specification only discloses a conjugate including an antibody, a linker, and a block copolymer including PEO and PPO (e.g. see lines 4-8 in page 11 of the specification as-filed); the instant claims now recite the block copolymer comprising PEO and PPO, wherein the PPO has a repeating unit number of 20 to 80, which were not clearly disclosed in the specification. Therefore, the claims represent a departure from the specification and claims originally filed.
Applicant’s reliance on generic disclosure (a conjugate including an antibody, a linker, and a block copolymer including PEO and PPO) and species of specific antibody conjugates without setting forth the number of repeats for PPO do not provide sufficient direction and guidance to the features currently claimed (antibody conjugate comprising a linker and a block copolymer comprising PEO and PPO, wherein the block copolymer is covalently linked to the linker, and PPO has a repeating unit number of 20 to 80). It is noted that a generic or a sub-generic disclosure cannot support a species unless the species is specifically described. It cannot be said that a subgenus is necessarily described by a genus encompassing it and a species upon which it reads. See In re Smith 173 USPQ 679 683 (CCPA 1972) and MPEP 2163.05.
Such limitations recited in the present claims, which did not appear in the specification, as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C. 112.
Applicant is required to cancel the new matter in the response to this Office Action.
Alternatively, applicant is invited to provide sufficient written support for the “limitations” indicated above. See MPEP 714.02, 2163.05-06 and 2173.05 (i).
6. 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.
7. 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.
8. Claims 1-3, 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) for the reasons of record.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant argues that the amended claims now recite an antibody, a linker linked to the antibody via an –S- bond or an amide bond and a block copolymer comprising PEO and PPO, wherein the block copolymer is covalently linked to the linker and the PPO has a repeating unit number of 20 to 80 which is not disclosed in Song et al. Applicant asserts that Song et al. teach nano-micelle (anti-HIF-1α nano-micelle PTX) formed by the self-assembly of terminal carboxyl-functionalized Pluronic P123 and paclitaxel with the antibody conjugated to its surface. Thus, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
Contrary to applicant’s assertion relying upon the self-assembly of nano-micelle in Song et al., note that the instant claims are drawn to the method of using a conjugate comprising an antibody, a linker -S- bond or amide bond, and a block copolymer comprising PEO and PPO, and the PPO has a repeat unit number of 20 to 80.
The transitional phrase “comprising” is open-ended and does not exclude additional, unrecited elements. See MPEP 2111.03.
Here, while copolymers PEO and PPO are self-assembled with paclitaxel in Song et al,. the C-terminals of the PEO (COOH) is conjugated to the N-terminal of the ant-HIF-1α antibody (NH2) via carbodiimide coupling chemistry which will form an amide bond, e.g. see Scheme 1 in page 3 or copy below:
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Therefore, Song et al. teaches a conjugate comprising an antibody linked to the block copolymer comprising PEO and PPO via an amide bond. Given that the instant claims recites “comprising” with respect to the conjugate, the named elements including antibody and copolymer linked via amide bond are essential but other elements (e.g. paclitaxel encapsulated with P123) can be added and still form a construct within the scope of the claims.
Further, Song et al. teaches that the copolymer Pluronic P123 consists of PEO35-PPO39-PEO35 (e.g. see 2.2.1. Preparation of nitrile-functionalized pluronic P123 copolymer in right col. in page 2). Therefore, the teachings of Song et al. also meet the newly added limitation of PPO having a repeat unit number of 20-80.
As such, the teachings of Song et al. anticipate the instant invention.
9. Claims 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) for the reasons of record.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant argues that Ding et al. do not teach the amended claims. Further, applicant asserts that Ding et al teach functional Pluronic F127 nano-micelle conjugated with anti-mesothelin antibody and quantum dots encapsulated within carboxylated F127 polymer micelles (F127COOH) ant the antibody is conjugated to the surface through an EDC activation reaction. Applicant asserts that Ding et al. teach the use of the conjugate in diagnosis of pancreatic cancer but do not teach the use of the conjugate. As such, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
Contrary to applicant’s arguments, note that the instant claims are drawn to the method of using a conjugate comprising an antibody, a linker -S- bond or amide bond, and a block copolymer comprising PEO and PPO, and the PPO has a repeat unit number of 20 to 80.
The transitional phrase “comprising” is open-ended and does not exclude additional, unrecited elements. See MPEP 2111.03.
Here, while Ding et al. teach carboxyl groups were introduced on the PEO terminal of F127 for the purpose of bioconjugation (e.g. see last paragraph in left col. in page 1814) which will form amide bond with the antibody in the presence of EDC (e.g. see conjugation of anti-mesothelin antibody on the surface of F127COOH-QD micelles in the left col. in page 1815). Further, Ding et al. teach that F127 consists of PEO98PPO67PEO98 (e.g. see Fig. 1 in page 1814).
Ding et al. teach that the anti-mesothein antibody conjugated carboxylated F127 nanomicelles can serve targeted drug delivery (e.g. see Abstract). Therefore, the teachings of Ding et al. anticipate the instant invention. Applicant’s arguments have not been found persuasive.
10. 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.
11. Claims 1-3 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), as evidenced by Khaliq et al. (Pharmaceutics 2023, 15;2102:1-25) and Faller et al. (Biologics: Targets & Therapy, 2009, 3:419-428), and in view of Park et al. (Biomaterials 2013, 1-9, reference on IDS).
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).
The teachings of Ding et al. 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 and a method for treatment of cancer in an individual by administering 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.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant’s arguments and the instant invention is drawn to a method by which an antibody-based target anticancer agent with strong antigen-antibody binding for an extended period. Applicant asserts that the instant invention provides an antibody based conjugate for cancer treatment with improved in vivo half life and therapeutic efficacy.
Applicant asserts that Ding et al. do not teach or suggest the use of the individual material constituting the nano-micelles. Applicant argues that Park teaches a complex of chlorine6 and Pluronic but asserts that there is no motivation in Ding to use the individual components constituting the nano-micelles. Applicant asserts that the present invention exhibits superior anticancer effect compared to the antibody alone and cannot be readily derived from the prior art cited here. Applicant asserts that Ding et al. teach anti-HIF-1α antibody for targeting cancer cells but does not teach whether the antibody has anticancer effect.
In response to applicant's argument that the references fail to show certain features of the invention such as strong antigen-antibody binding for extended period or improved half-life and therapeutic efficacy, it is noted that these features upon which applicant relies are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Further, in contrast to applicant’s assertion relying upon superior anticancer effect of the conjugate compared to antibody alone, note that the working examples in the instant specification disclosing specific known anti-cancer antibodies such as cetuximab, trastuzumab, or avelumab antibody conjugates are not commensurate in scope with the instant method claims 1-3 and 7-10 that drawn to a method for treatment of unspecified cancer by administering a conjugate comprising any antibody a linker an -S- bond, or an amide bond, and a block copolymer comprising PEO and PPO with a repeating unit number of 20 to 80.
Furthermore, in response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Ding et al. teach mesothelin is overexpressed in pancreatic adenocarcinoma and anti-mesothelin antibody conjugated with carboxyl group of F127COOH would specifically target pancreatic cancer; the resulting anti-mesothelin antibody-F127 conjugate have good chemical and colloid stability, good solubility in aqueous buffer, enhanced tumor targeting efficient and low toxicity and can serve as diagnostic platform and subsequence therapy of pancreatic cancer and other cancer (e.g. paragraph spanning left and right cols. in page 1814). Park et al. teach that PF127 when conjugated with photosensitizer Ce6 shows enhanced cytotoxicity against mouse xenograft with colon cancer cells.
As such, combining anti-mesothelin 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 pancreatic cancer treatment.
As such, applicant’s arguments have not been found persuasive.
12. No claim is allowed.
13. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
14. 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.
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/CHUN W DAHLE/Primary Examiner, Art Unit 1641
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