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 ACTION
Status of Application, Amendments, and/or Claims
The Information Disclosure Statement (IDS) filed 6 June 2024 has been entered. Applicant’s amendment of the claims filed 2 December 2025 has been entered.
Election/Restriction
Applicant’s election, without traverse, of Group II, claims 10-12, in the reply received on 2 December 2025 is acknowledged. In the response, Applicant further elected the species of: A) wherein the VH domain specific for CD99 having the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs: 1, 5 and 8, respectively, and the VL domain specific for CD99 having the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs: 12, 16 and 19, respectively; and G) wherein the fusion polypeptide comprising the formula of VLI - VHI - VLT - VHT.
Claims 1-9 and 12 are cancelled. Claims 10, 11 and 13 are pending. Claim 13 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 10 and 11 are under examination to the extent they read on the elected species.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because of the following informalities:
Paragraph [0001] of the specification has a typographical error, U.S. Provisional Application Serial No: 62/641,779 should be 62/614,779.
U.S. Patent Application No. 16/960,656 is now patented. The first paragraph of the specification should be updated accordingly.
Appropriate correction is required.
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.
Claim 10 is 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.
Claim 10 recite “the amino acid sequence SEQ ID NO:16”. However, in the sequence listing, there is no sequence for SEQ ID NO: 16.
Claim Rejections - 35 USC § 112
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.
Claims 10 and 11 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 claims contain 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.
Independent claim 10 is directed to a fusion polypeptide comprising a formula: VLI - VHI - VLT - VHT, wherein VHT and VLT correspond to a heavy chain variable domain and a light chain variable domain specific for CD99, and VHI and VLI correspond to a heavy chain variable domain and a light chain variable domain specific for an immune cell antigen. Claim 10 further defines the amino acid sequences of the three CDRs of the VHT and VLT, and depending claim 11 limits “wherein the immune cell antigen is CD3”.
The claims are broad and encompass a genus of fusion polypeptides, however, the specification fails to provide adequate written description and evidence of possession of the genus of molecules. The specification describes that “The immune cell antigen can be a cell surface molecule that is expressed on human NK cells, T cells, monocytes, macrophages or granulocytes.” The specification, however, does not adequately describe the structural characteristics (e.g., the sequences of VH and VL, or the CDRs comprised therein) of the antigen-binding domains specific for the cell surface molecules expressed on human NK cells, T cells, monocytes, macrophages or granulocytes, nor for the antigen-binding domains specific for CD3, which are encompassed by the instant claims. Merely providing the antigen alone is not sufficient for adequate written description of the antibody itself. In Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), the Federal Circuit explained that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself (emphasis added), and that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010). Adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional. Id. It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy chain and light chain variable regions of a given antibody, each of which includes three CDRs or hypervariable regions which provide the majority of the contact residues for the binding of the antibody to its target epitope (see Knappik et al., J. Mol. Biol., 2000, Vol. 296(1):57-86). Even for a single epitope, there could be numerous antibodies that have distinct antigen-binding domains. For example, Nair et al. (2002, J. Immunol., Vol. 168(5):2371-2382) teaches that monoclonal antibodies that bind to the same epitope have dissimilar binding site structures (see Abstract). The prior art does not teach how to predict the structures of the antibodies that bind to a disclosed epitope, let alone a full-length protein. A skilled artisan cannot envision the detailed structures of the encompassed genus of antigen-binding domains specific for a cell surface molecule, including CD3, expressed on human NK cells, T cells, monocytes, macrophages or granulocytes. Based on the lack of knowledge and predictability in the art, those of ordinary skill in the art would not conclude that the Applicant was in possession of the claimed genus of fusion polypeptides.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making of the claimed product, or any combination thereof. In this case, there is no sufficient teaching regarding the correlation of structure and function, nor identification of any particular structure that must be conserved. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states 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). As discussed above, the skilled artisan cannot envision the detailed structures of the encompassed genus of molecules, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that is part of the invention and reference to a method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Therefore, the disclosure does not meet the requirement of adequate written description for the claimed fusion polypeptides as claimed.
Claims 10 and 11 are further 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 claims contain 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.
As discussed above, the claims encompass a genus of fusion polypeptides, however, the specification fails to teach sufficient structural characteristics of these molecules, and there is no sufficient teaching regarding the correlation of structure to function. In the absence of the guidance from the specification, a skilled artisan cannot envision the detailed structures of these fusion polypeptides, therefore, would not know how to make these molecules.
Further, the specification is not enabled for using the genus of molecules. The claims do not specify what function/activity these molecules have. While the specification discloses that blocking CD99 may provide targeted treatment of CD99-expressing cancers, the specification, however, fails to teach what immune cell antigen can be combined or co-targeted with an anti-CD99 moiety in a fusion polypeptide. Zhou et al. (Mol. Cancer, 2023, Vol. 22:34) teaches that various cell surface proteins on NK cells can be either involved in enhancement or inhibition of NK cells (see Fig. 3). A skilled artisan would not be able to predict the activities, nor readily know how to use the fusion polypeptides, e.g., a fusion polypeptide that simultaneously blocks CD99 and inhibits NK cell activities. Further, Lu et al. (J. Immunol., 2004, Vol. 173(6):3972-3978) teaches that a monoclonal antibody (e.g., directed against the integrin subunit) can exhibit an antagonistic or agonistic activity. In the absence of guidance from the specification, one skilled in the art would perform undue experimentation to determine what functions/activities these molecules have and how to use them, which does not satisfy the enablement requirement under 35 U.S.C. 112(a).
Clearly, the instant specification does not enable one of skill in the art to make and use the broad genus of fusion polypeptides. See In re Wands', 858 F.2d at 737, 8 USPQ2d at 1404. The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue. The factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue" include, but are not limited to: (1) the breadth of the claims; (2) the nature of the invention; (3) the state of the prior art; (4) the level of one of ordinary skill; (5) the level of predictability in the art; (6) the amount of direction provided by the inventor; (7) the existence of working examples; and (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Given the breadth of the claims, in light of the predictability of the art as determined by the number of working examples, the level of skill of the artisan, and the guidance provided in the instant specification and the prior art of record, it would require undue experimentation for one of ordinary skill in the art to make and use the claimed invention.
Conclusion
NO CLAIM IS ALLOWED.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Xiaozhen Xie, whose telephone number is 571-272-5569. The examiner can normally be reached on M-F, 8:30-5.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa L. Ford, can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/XIAOZHEN XIE/Primary Examiner, Art Unit 1674