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 .
Status of Claims
Claims 1-8 are currently pending and under examination on the merits in the instant application.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Specification
The abstract of the disclosure is objected to because the word “novel” is not descriptive of an invention. In addition, the first sentence of the abstract is grammatically incorrect. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because the Brief Description of the Drawings for FIG. 6C-6P fails to describe what each of the numbers (e.g., “2’” in FIG. 6F and “7” in FIG. 6L and 6M) means. Appropriate correction is required.
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 1-8 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.
For examination purpose, the phrase “sequence represented by” recited in multiple claims in the instant application will be interpreted as “the” amino acid or nucleic acid “sequence of” the recited SEQ ID NO. For instance, “encoding an amino acid sequence represented by SEQ ID NO:3” in claim 1 will be interpreted as “encoding the amino acid sequence of SEQ ID NO:3.”
It is noted that the instant specification is completely silent regarding the actual “polynucleotide” sequence that encodes the 242 amino acid residues of SEQ ID NO:3 claimed in the instant case. That is, the specification does not disclose a single coding nucleotide sequence “for cancer treatment” that in fact encodes the art-unrecognized, previously unknown amino acid sequence of SEQ ID NO:3. The specification’s disclosure of the non-coding sequence elements such as the 5’ UTR (e.g., SEQ ID NO:19), 3’ UTR (e.g., SEQ ID NO:20), NLS (e.g., SEQ ID NO:23), and MLS (e.g., SEQ ID NO:24) is not an adequate written description of the required “novel polynucleotide”, which is a coding sequence that is claimed to encode the purportedly a “novel” protein sequence of SEQ ID NO:3. See page 2 of the specification. As such, the instant specification fails to describe the allegedly inventive, “novel” polynucleotide sequence claimed in the instant case while disclosing non-coding nucleotide sequences such as the 5’ UTR, 3’ UTR, NLS, and MLS as explained above. In other words, the instant specification is completely devoid of a written description of the claimed subject matter: the polynucleotide (e.g., mRNA) sequence encoding SEQ ID NO:3, wherein the polynucleotide is “for cancer treatment”. Since the claimed polynucleotide encoding SEQ ID NO:3 is expressly described as “a novel polynucleotide” that is new and unknown in the prior art, the instant specification must disclose the newly discovered “novel polynucleotide” sequence claimed in the instant case in order to comply with the written description requirement since the specificity of the disclosure inversely correlates with the prior art knowledge. See MPEP §2163. Hence, the instant specification’s complete lack of an actual polynucleotide sequence having the intended use “for cancer treatment” is insufficient to adequately describe which nucleotide sequence encoding SEQ ID NO:3 has the claimed intended function.
It is noted that the specification merely mentions that the instant co-inventors “named ‘T001’ (SEQ ID NO: 3)” and also merely discloses the name “T001 mRNA” as having an anti-cancer effect in cancer cell lines. See pages 15 and 31-33. However, the specification does not disclose the nucleotide sequence of “T001 mRNA”. The instant specification further discloses that the anti-cancer effects observed in cancer cell lines in vitro by “T001 mRNA” are achieved by a “sequence optimization process of T001”, wherein “natural codons were replaced”. See pages 15-16. That is, if “T001 mRNA” indeed corresponds to a polynucleotide encoding SEQ ID NO:3, the “novel”, codon-optimized nucleotide sequence encoding an anti-cancer drug that is “named ‘T001’ (SEQ ID NO: 3)” is concealed from the public as the specification is completely silent regarding the actual nucleotide sequence of “T001 mRNA” in spite of the fact that the instant co-inventors presumably knew and had possession of the exact nucleotide sequence of “T001 mRNA” encoding SEQ ID NO:3 in order to make and use “T001 mRNA” for performing in vitro transfection of the “T001 mRNA”. Note that “applicant must not conceal from the public the best way of practicing the invention that was known to the patentee at the time of filing the patent application. Failure to fully comply with the disclosure requirements could result in the denial of a patent, or in a holding of invalidity of an issued patent.” See MPEP §2162.
Now, as noted above, the instant specification at best describes an undisclosed codon-optimized nucleotide sequence encoding SEQ ID NO:3 may be used “for cancer treatment”. The very fact that the single polynucleotide shown to have the potential intended use claimed in the instant case is codon-optimized implies that the claimed polynucleotide encompasses a myriad of modified, codon-optimized nucleotide sequence species encoding a potential anti-cancer drug that is “named ‘T001’ (SEQ ID NO: 3)”. Note that because of the degeneracy of the genetic code, there are a vast number of nucleotide sequences that might code for a specific protein, wherein the process of codon-optimization would further increase the number of nucleotide sequences that might code for the claimed amino acid sequence of SEQ ID NO:3, wherein the specific codon-optimized sequence of “T001 mRNA” shown to provide apoptosis in cancer cell lines is not disclosed in the specification. Since the instant specification provide no information/disclosure pertaining to the specific codon-optimized nucleotide sequence of “T001 mRNA”, a person of ordinary skill in the art would not know which specific nucleotide sequence qualifies as “T001 mRNA” for providing the apoptosis of colon cancer cell line (HCT-116) and triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468). Moreover, claims 1-3 and 5-8 recite that the claimed mRNA “inhibits nucleic acid metabolism.” The instant specification at best speculates that the undisclosed mRNA sequence is “predicted” to contribute to “selective deficiency of specific nucleic acids and dTTP in the substrate”, thereby causing cell cycle arrest and “will eventually induce apoptosis”. See page 30. Hence, the genus of “nucleic acid metabolism” inhibition is not described by the mere name “T001 mRNA”; rather, such function is merely speculated only for inhibiting dTTP metabolism.
The functionality/activity of a codon-optimized nucleic acid has long been known to significantly differ from an unmodified, wild-type, native nucleic acid. See for instance Urbatsch (US 2013/0011909 A1) demonstrating the drastically different in vivo biological activity in relative growth of S. cerevisiae with a statistical significance between the wild-type P-glycoprotein sequence (“WT-Pgp”) and the codon-optimized sequence (“Opti-Pgp”) in the presence of FK506 as shown in Figure 4C reproduced below.
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See also Chou et al. (US 2016/0376608 A1) demonstrating the in vivo hepatic activity of the codon-optimized G6Pase (“GPE-co-G6Pase”) is different with a statistical significance compared to that of the unmodified G6Pase (“GPE-G6Pase”) as shown in Figure 11. Similarly, Lin et al. (Vaccine, 2016, 34:134-141) demonstrate that tumor volume reduction provided by the codon-optimized GM-CSF sequence (“TC-1/cGM”) significantly differs from that provided by an unmodified wild-type GM-CSF sequence (“TC-1/wtGM”) as shown in Figure 3B reproduced below.
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In view of the relevant prior art knowledge that the actual biological activity of a polynucleotide encoding a protein significantly differs depending on the actual polynucleotide sequence encoding the protein as evidenced by the teachings of Urbatsch, Chou, and Lin, one of ordinary skill in the art would reasonably conclude that the instant specification’s complete absence of an actual polynucleotide sequence encoding SEQ ID NO:3 is insufficient to describe the actual species “T001 mRNA” having the function of treating cancer, let alone countless nucleotide sequence variants within the instantly claimed genus. Again, the instant specification merely discloses a single, codon-optimized polynucleotide species by a name that is called “T001 mRNA” without the actual disclosure of the codon-optimized nucleotide sequence included therein (thus equivalent to disclosing no nucleotide sequence species), wherein the mere name “T001 mRNA” is far from representing the substantial variation of the nucleotide sequence species variety encompassed by the claimed genus of polynucleotides encoding SEQ ID NO:3, wherein the polynucleotides have the intended function “for cancer treatment”. The mere name “T001 mRNA” that is arbitrarily assigned in the instant application cannot describe an actual codon-optimized sequence providing the recited functions in the instant claims thus the instantly claimed polynucleotide is not adequately described in “full, clear, concise, and exact terms” as required by 35 U.S.C. 112(a). Furthermore, even if the instant specification were to expressly disclose the single species of the codon-optimized “T001 mRNA” encoding SEQ ID NO:3, the single mRNA sequence is not a representative number of species within the claimed genus in view of the art-recognized unpredictability in biological activity/function that is highly dependent on the actual nucleotide sequence as evidenced by the teachings of Urbatsch, Chou, and Lin. That is, the single mRNA sequence, if indeed disclosed in the instant specification, is not representative of a myriad of other nucleotide sequence variants encoding SEQ ID NO:3 as one of ordinary skill in the art would reasonably expect a high level of nucleotide sequence-dependent unpredictability pertaining to the “cancer treatment” function or inhibiting nucleic acid metabolism.
Note that “when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)(“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”).” See MPEP §2163.
In view of the foregoing, it is concluded that the specification fails to provide an adequate written description “in such full, clear, concise, and exact terms” of the purportedly codon-optimized polynucleotide “T001 mRNA” encoding a protein that is “named ‘T001’ (SEQ ID NO: 3)”, much less the instantly claimed “polynucleotide” genus without any specific SEQ ID NO thus encompassing a substantial variation of nucleotide sequences encoding SEQ ID NO:3. Therefore, the instant specification fails to put the public in possession of the claimed “polynucleotide for cancer treatment” as of the filing date sought in the instant application.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of copending Application No. 18/021,097 (now allowed).
Note that this rejection will change to a non-provisional rejection once an issue fee is paid in the ‘097 application.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instantly claimed polynucleotide is anticipated by the ‘097 claims that require and recite the same polynucleotide claimed in the instant case, namely, a polynucleotide (mRNA) encoding SEQ ID NO:3, which is 100% identical to SEQ ID NO:3 claimed in the instant case.
Relevant Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. McCandliss et al. (US 5,213,972 A) disclose a nucleotide sequence in FIG. 7b encoding thymidylate phosphohydrolase comprising amino acids 1-242 of SEQ ID NO:3 of the instant application with 5 mismatched amino acid residues 1 (Met), 2 (Val), 14 (Asp), 133 (Glu), and 200 (Thr) relative to SEQ ID NO:3 of the instant application.
Conclusion
No claim is allowed.
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/DANA H SHIN/Primary Examiner, Art Unit 1635