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. Claims 1, 2, 7, 9, 11, 13, 16, 18, 21, 25, 28, 29, 33, 36, 41-43, 46, 48-51, 56, 57, 64, 65 and 69 are pending upon entry of amendment filed on 6/7/23.
Claims 1, 2, 7, 9, 11, 13, 16, 18, 21, 25, 28, 29, 33, 36, 41-43, 46, 48-51, 56, 57, 64, 65 and 69 are under consideration in the instant application.
3. Applicant’s IDS filed on 9/7/23 and 5/23/25 have been acknowledged. The non-English patent documents have been considered to the English abstracts. English translation is required if further consideration is required.
4. The oath filed on 6/7/23 has been acknowledged.
5. Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C.119(a)-(d).
6. Claim 69 is drawn to “use” of composition are subject to rejection under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e. results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ 678(Bd. App.1967) and Clinical Products, Ltd v Brenner, 255 F Supp.131, 149 USPQ 475 (D.D.C.1966).
7. 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.
8. Claims 21, 28, 29, 49, 65 and 69 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 pre-AIA the applicant regards as the invention.
The use of the term “optionally” in claims 29, 49 and 65, renders the claim indefinite because it is unclear whether the limitations following such terms or phrases are part of the claimed invention. See MPEP 2173.05 (h).
Further, in claims 21 and 28 uses “an amino acid sequence set forth in SEQ ID NO”. IN sequence analysis, use of “an amino acid sequence” reads on a fragment of the sequence while “the amino acid sequence” reads on an entire or full-length amino acid sequence. Appropriate correction is required.
Moreover, claim 69 recites improper Markush language. The phrase “is selected from the group consisting of A, B, C and D” is required. See MPEP 2173.05 (h).
9. 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 inventio
10. Claims 1, 2, 7, 9, 11, 13, 16, 18, 21, 25, 28, 29, 33, 36, 41-43, 46, 48-51, 56, 57, 64, 65 and 69 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a protein-drug conjugate set forth in SEQ ID NO: 59-71, 106-129, 148 or 149 and method of preparing or analyzing of protein-drug conjugate, does not reasonably provide enablement for more.
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/or use of the invention commensurate in scope with these claims.
The specification does not enable one of skill in the art to practice the invention as claimed without undue experimentation. 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 specification of the instant application does not describe how to make and use the protein-drug conjugate as in SEQ ID NO:59-71, 106-129, 148 or 149. Although instant application describes how to make and analyze PR00020, PR000184, PR000759, PR01046, PR004432, PR004433, PR002129, PR000453, PR006345 as in tables in p. 65-66, in lack of specific conjugate moiety, the specification does not provide sufficient guidance for any unspecified antigen binding fragments, linkers and the linkers comprise Cys1 and/or Cys2 as specified in claims, 1, 7 and 9 reciting linkers derived from antibody hinge regions.
Moreover, there is insufficient guidance in the specification as filed as to how the skilled artisan would use protein-drug conjugate in treatment or prevention of cancer. The examples of instant specification disclose coupling, reduction and analysis of but the specification fails to disclose any treatment regimen required by the claims 65 and 69.
Although examples 1-13 showed coupling and analysis of various hinge regions of protein-drug conjugates, the specification fails to disclose prevention, treatment of cancer using the protein-drug conjugates. Tumor antigens are recited in claim 19 but claims 65 or 69 that is being depended on claim 1 does not recite any structurally specified tumor antigens or the specification of the instant application fails to disclose any protein-drug conjugate used in cancer treatment and prevention. As seen in WO2017/201449, the PROTAC antibodies may associated with cytotoxic activities and prepare cysteine engineered antibody, no effective cancer treatment or regimen is suggested for the cancer recited in claim 65 and 69 (see entire document).
The specification fails to provide sufficient guidance to direct a person of skilled in the art to make and achieve the intended use of the claimed invention without undue experimentation. It is unpredictable to develop antibody formulation and one exemplary formulation disclosed in the example cannot be extrapolated to various formulations encompassed by the claimed invention.
To summarize, reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view or the quantity of experimentation necessary, the limited working example, the unpredictability of the art, the lack of sufficient guidance in the specification, and the breath of the claims, it would take undue trials and errors to practice the claimed invention.
11. Claims 1, 2, 7, 9, 11, 13, 16, 18, 21, 25, 28, 29, 33, 36, 41-43, 46, 48-51, 56, 57, 64, 65 and 69 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Specifically, there is insufficient written description to demonstrate that Applicant was in possession of the claimed genus of any protein-drug conjugates with unspecified antigen binding fragments, linkers and the linkers comprise Cys1 and/or Cys2 as specified in claims, 1, 7 and 9 reciting linkers derived from antibody hinge regions.
The guidelines of the Examination of Patent Applications Under the 35 U.S.C. 112, §1 “Written Description” Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicant was in possession of the genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001, see specially page 1106 column 3).
The guidelines of the Examination of Patent Applications Under the 35 U.S.C. 112, §1 “Written Description” Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicant was in possession of the genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001, see specially page 1106 column 3, MPEP2163).
In The Reagents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F.3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted: A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. See Fiers, 984F. 2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statue requires a description of an invention, not an indication of a result that might achieve if one made that invention. See In re Wilder 736 F.2d 1516,1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”). Accordingly, naming the type of material generally known to exist, in the absence of knowledge as to what that material consist of, is not a description of that material”.
The court has further stated that “Adequate written description requires a precise definition such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention”. Id. At 1566, 43 USPQ2d at 1404 (quoting at 1171, 25 USPQ2d at 1606). Also see (CAFC2002). Enzo-Biochem v. Gen-Probe Fiers, 984 F.2d 01-1230.
The instant claims are drawn to huge genus of any protein-drug conjugates with unspecified antigen binding fragments, linkers and the linkers comprise Cys1 and/or Cys2 as specified in claims, 1, 7 and 9 reciting linkers derived from antibody hinge. Although instant application describes how to make and analyze SEQ ID NO:59-71, 106-129, 148 or 149 as in PR00020, PR000184, PR000759, PR01046, PR004432, PR004433, PR002129, PR000453, PR006345 of tables in p. 65-66, no other conjugate is no described. This would encompass any structurally unrelated drug substance including small molecules, nucleic acids, antibodies, peptides, lipids and more. There is no art recognized correlation between structure and function of such classes of the molecules and modulators exhibiting the claimed specific functions. The instant specification does not disclose a correlation between structure of the drug substances and protein drug conjugates with unspecified antigen binding fragments, linkers and the linkers comprise Cys1 and/or Cys2 with the various functions claimed. Further, the disclosed species are not sufficiently representative of the huge genus encompassed by the present claims. Thus, one of skilled in the art would conclude that the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus of the claimed protein drug conjugates. See Eli Lilly, 119 F, 3d 1559, 43, USPQ2d, 1398.
12. 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 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.
13. 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.
14. Claim(s) 1, 2, 7, 9, 11, 13, 16, 18, 21, 25, 28, 29, 33, 36, 41-43, 46, 48-51, 56, 57, 64, 65 and 69 is/are rejected under 35 U.S.C. 102(a)(1)(2) as being anticipated by U.S. Pub. 2019/0175612.
The ‘612 publication teaches protein drug conjugates comprising PROTAC and the antibody includes EGFR and HERS (p.21-41, 43-62 table 4). The PROTAC conjugates include at least 2 linkers and covalently binds antibodies and drug (p.2) and the antibody includes VH, ScFv and VL (note p.3-5).
Claims 21 and 28 are included in this rejection as the claims recite “an amino acid of SEQ ID Nos” which read on a fragment. Applicant is advised to limit to the amino acid sequences comprising the SEQ ID Nos.
Further, as is evidenced by the claims 25, 29, 33 and 57, by having the PROTAC as protein-drug conjugate, the PROTAC would inherently include the hinges, linkers and antigen binding fragments as in claims 1, 2, 7, 9, 11, 16, 18 and 25 of the instant application.
In addition, the ‘612 publication teaches cysteine engineered antibody variants (p. 16) with corresponding EU sequences, linkers (p. 41-42, 64-66), synthesis and analysis of PROTAC (p. 43-35, 76-79) readable upon method of making protein-drug conjugates. Moreover, the ‘612 publication teaches use of CD-33 and HER2/MUC16 PROTAC in treatment of gastric cancer (p.81). Therefore, the reference teachings anticipate the claimed invention.
15. No claims are allowable.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to YUNSOO KIM whose telephone number is (571)272-3176. The examiner can normally be reached Mon-Fri 8:30-5.
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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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Yunsoo Kim
Patent Examiner
Technology Center 1600
December 23, 2025
/YUNSOO KIM/Primary Examiner, Art Unit 1641
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