CTNF 18/245,819 CTNF 78522 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Applicant’s election and amendment filed February 6, 2026 is acknowledged. Group I, Claims 1-9, 11, 13-24, 26 and 28-31 and species election A, Structure I is acknowledged. Claims 10 and 25 are withdrawn. Claims 12 and 27 have been canceled. Claims 1-9, 11, 13-24, 26 and 28-31 are under examination. Specification The use of the term for example, Alexa Fluor® (page 51) (which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Please, review the specification for other trademarks and make the appropriate corrections. The specification is objected to disclosing text that appear to resemble claim language. See pages 102-211. Correction is required. Claim Rejections - 35 USC § 112 07-30-01 AIA 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. 07-31-01 Claims 1-9, 11, 13-24, 26 and 28-31 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. The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical 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 Applicants were in possession of the claimed genus. The claims are drawn to a molecule comprising (i) a targeting moiety (ii) at least one payload wherein said payload is a therapeutic agent or a detectable label,(iii) a linker covalently linking said payload and said targeting moiety, and(iv) at least one solubility tag, wherein said solubility tag comprises a chito-oligosaccharide of at least 3 and up to 12 monosaccharide units. The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.” The instant specification teaches that in the context of the invention, claims encompass a genus of conjugates comprising any targeting moiety, any payload, and at least one solubility tag that is a chito-monosaccharide of at least 3-12 monosaccharide units. However, the specification only discloses conjugates comprising specific payloads and CO-V (a specific oligosaccharide; tag see paragraph 0546). (See table 2). The encompassed molecules have no correlation between their structure and function. Therefore, the specification provides insufficient written description to support the genus encompassed by the claim. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.) The skilled artisan cannot envision the detailed chemical structure of the encompassed polypeptides, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence. University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that: ...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2datl966. The state of the art regarding antibody drug conjugates (ADCs), therapeutic modality is highly unpredictable. Zhou et al (ScienceDirect, Volume 6, Issue 10, 10 October 2025) teach that antibody-drug conjugates (ADCs) have advanced cancer therapy by combining antibody specificity with cytotoxic potency. However, clinical experience has revealed challenges limiting their efficacy and safety and emerging payload strategies like immune-stimulating ADCs (ISACs) and degrader-antibody conjugates (DACs) expand therapeutic possibilities but introduce new safety challenges. Ultimately, merely increasing ADC structural complexity is insufficient. (see the Abstract). Zhou et al teach while ADCs initially appeared as a rising star in oncology, their extensive clinical evaluation also revealed significant challenges. A long-standing debate centers on their therapeutic window. Theoretically, ADCs should expand this window by combining antibody-mediated targeting with cytotoxic payloads: the antibody’s specificity reduces off-target payload exposure, while concentrated tumor delivery enhances efficacy, aligning with Paul Ehrlich’s magic bullet concept of targeted, healthy-tissue-sparing therapy. Yet, clinical evidence contradicts this. Meta-analyses show that ADCs rarely achieve a higher maximum tolerated dose (MTD) in humans than conventional chemotherapies, despite preclinical safety signals. Off-target toxicities persist: unstable linkers cause premature payload release in circulation, while overly stable ones trigger on-target, off-tumor toxicity in normal tissues with target antigen expression. Compounding this, only 0.1%–2% of administered ADCs reach the tumor, prompting questions about whether their clinical benefits stem from true targeting or prolonged drug exposure due to the antibody’s half-life (see the Introduction). Wang et al (Acta Pharmaceutica Sinica B 2023;13(1):4025-4059) teach due to clinical limitations of traditional ADC payloads, such as inadequate efficacy and the development of acquired drug resistance, novel highly efficient payloads with diverse targets and reduced side effects are being developed (see the Abstract). Wang et al teach although ADCs have gone through three generations, current payloads still have clinical limitations such as severe side effects and the development of drug resistance. There is still a strong unmet medical need to develop more potent ADC payloads, ideally with better therapeutic indexes (page 4026). Wang et al teach payloads are an important part of the ADC design. The activity and physicochemical properties of the payload have a direct impact on the antitumor efficacy of ADC drugs. The mechanism of action of the payload is an important factor determining the performance of the ADC (e.g., adverse reactions). Besides, certain other characteristics of ADC payloads, such as cytotoxicity, immunogenicity, stability of storage during preparation and circulation, water solubility, and modifiability are also important (see page 4026-4027). Wang et al also discloses that there are various target payloads (pages 4030-4054). Wang et al conclude although the specificity and cytotoxicity of the new generation ADC payloads have shown significantly improved characteristics than those in the early stages, the current payloads still have some limitations. First, they generally have limited solid tumor permeability and toxicity, which limits their applications to solid tumors. Second, some tumors are insensitive to current ADC drugs. Third, the complexity of payload pharmacokinetics, tumor targeting, and insufficient release can all affect the efficacy of ADC drugs. Fourth, like other antitumor drugs, ADC drugs can also develop resistance. Finally, earlier payload selection tends to be toxic but effective drugs, but their higher toxicity limits the systematic application of the payload. Although the antibody-drug conjugates show effectiveness in treatment, the combination with highly toxic payloads is not necessarily excellent. Applicant is reminded that generally, in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus (Enzo Biochem, Inc. v. Gen- Probe Inc., 323 F.3d 956 (Fed. Cir. 2002); Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004); Regents of the University of California v. Eli Lilly Co., 119 F.3d 1559 (Fed. Cir. 1997)). A patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017) at page 1358). An adequate written description must contain enough information about the actual makeup of the claimed products — “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361). MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the "written description" requirement is broader than to merely explain how to "make and use"; the Applicant must convey with reasonable clarity to those skilled in the art, that as of the filing date sought, he or she was in possession of the invention. The invention is for purposes of the “written description” inquiry, whatever is now claimed. See Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed. Therefore for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed. 07-30-02 AIA 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 7 and 22 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. Claims 7 and 22 recite “capable of”. The targeting moiety should bind to the tumor antigen which more than merely being “capable of” performing the function. Clarification/correction is required. Claim 18, 19, 28 and 31 recite “chemically modified forms of said aldoses or ketoses” and “chemically modified forms of tetroses, pentoses, hexoses” is not defined and it is unclear what is encompassed by the term. Clarification/correction is required. 12-151 AIA 26-51 12-51 Status of Claims No claims allowed. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to Vanessa L Ford whose telephone number is (571) 272-0857. The examiner can normally be reached Monday to Friday 9:00 -5:30 EST. 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, Yvonne Eyler can be reached at 571.272.1200. 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. /VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674 Application/Control Number: 18/245,819 Page 2 Art Unit: 1674 Application/Control Number: 18/245,819 Page 3 Art Unit: 1674
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