DETAILED ACTION
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 .
Claims 1-6 and 9-11 are pending and under consideration.
Information Disclosure Statement
The Information Disclosure Statement filed on 8/3/2023 has been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see pg. 4, line 21, pg. 9, last line). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Brief Description of the figures
The disclosure is objected to because of the following informalities: The Brief description is inconsistent with Figure 1. The brief description describes it as Figure 1, whereas the Drawing is labeled as FIG. 1A and FIG. 1B. Similarly, the Brief description describes Figure 2, but the Drawing is labeled as FIG.2A and FIG.2B. Applicants are suggested to either amend the brief description of the drawing or in alternate replace the drawings.
Claim Objections
Claim 1 is objected to because of the following informalities: claim 1 is objected for the use of an abbreviated phrase (PD-1), which should be described for the first time followed by an abbreviated form placed in a bracket.
. 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 2 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.
Regarding claim 2, the phrase "an amino terminal segment to increase its expression in bacteria" renders the claim indefinite because it is unclear how many amino acids of the antigen of SEQ ID NO: 1 comprises N-terminal segment that is responsible for increased expression in bacteria. The specification does not disclose a segment that is responsible for structure and function relationship. Therefore, metes and bounds of the claim cannot be determined.
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 1-6 and 9-11 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 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 in this case only sets forth a chimeric antigen having amino acid sequence of SEQ ID NO: 1 comprising an extracellular domain of the human programmed death ligand 1 (PD-L1) with reduced binding capacity of the programmed cell death protein 1 (PD-1) and CD80 receptors as compared to the native forms of PD-L1, and therefore the written description is not commensurate in scope with “a chimeric antigen comprising the extracellular domain of human PD-L1 which forms multimeric aggregates with reduced binding capacity to the PD-1 and CD80 receptors as compared to the native PD-L1 or up to 5% variant thereof ”.
The claims broadly encompass a chimeric antigen comprising the extracellular domain that forms multimeric aggregates with reduced binding to the PD-1 and CD80 receptors as compared to the native form of PD-L1. The claims do not require that a comprises N-terminal of 47 amino acid from LpdA protein from Neisseria meningitidis or any other peptide or structure required for multimeric aggregation.
The specification on pg.4, discloses that the amino acid sequence of SEQ ID NO: 1 comprises N-terminal 47 amino acid from Neisseria meningitidis and a linker of 13 amino acids that separates both peptides (N-terminal 47 amino acids with PD-L1). To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. Some of the factual considerations that are weighed when determining a written description include the level of skill and knowledge in the art, the disclosure of complete or partial structures, the disclosure of physical and or chemical properties, adequate disclosure of the functional characteristics, the correlation between structure and function, and disclosure of methods of making.
In the instant case, the specification at pg. 4 only adequately discloses that the amin acid sequence of SEQ ID NO: 1 comprises N-terminal 47 amino acid from Neisseria meningitidis which is separated from PD-L1 by a linker of 13 amino acids. The specification does not describe any other peptide or mutants at the N-terminus of the claimed antigen which includes up to 5% (up to 14 amino acids) variants of 290 amino acid long chimeric antigen that contributes to the feature of the multimeric aggregation of the chimeric antigen responsible for reduced binding with PD-1 and CD80. The specification does not describe the term “the extracellular domain of PD-L1” and what would be the variant amino acid positions in relation to amino acid sequence of SEQ ID NO: 1 that can still achieve the result of multimeric aggregation for reduced binding with PD-1 and CD80 receptors. The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed.
WO 2018/167290 (presented in the IDS) teaches that the human PD-L1 comprises the extracellular domain from amino acid 19 to 238 (pg.4, [0016]). WO 2017/201131 (Presented in the IDS) teaches variants of PD-L1 as immune modulating polypeptide (abstract). The problem of predicting protein structural determinations from an amino acid sequence to ascertain functional aspects of the protein is extremely complex. While it is known that many amino acid substitutions are generally possible in any given protein the positions within the protein's sequence where such amino acid substitutions can be made with a reasonable expectation of success are limited. Certain positions in the sequence are critical to the protein's structure/function relationship, e.g. such as various sites or regions directly involved in binding, activity and in providing the correct three-dimensional spatial orientation of binding and active sites. These regions can tolerate only relatively conservative substitutions or no substitutions ( Wells, 1990, Biochemistry 29:8509-8517).
Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, 1 "Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.
Vas-Cath Inc. V. Mahurka, 19 USPQ2d 1111, 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, for purposes of the written description inquiry, is 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).
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B (1), the court states an adequate written description of a DNA ... 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.
As discussed above, the skilled artisan cannot envision the detailed genus of “any chimeric antigen that comprises the extracellular domain of human PD-L1 which forms multimer aggregation with reduced binding to the PD-1 and CD80 receptors as compared to the native form of PD-L1” and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of making a mutation. The compound itself is required. See Fiers v.Revel, 25USPQ2d 1601 at 1606 (CAFC 1993) and Amgen v.Baird, 30 Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 148 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.
Therefore, only a chimeric antigen having amino acid sequence of SEQ ID NO:1 that forms multimeric aggregates with a reduced activity to the PD-1 and CD80 receptors as compared to the native form of PD-L1, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112, first paragraph.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision (see page 1115).
Conclusion
No claim is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674