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 .
Claim Objections
Claims 4-26 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, claims 4-26 have not been further treated on the merits.
Claim 3 is objected to because of the following informalities: Claim 3 recites that the nucleotide sequence that encodes the signal peptide comprises a nucleotide sequence of SEQ ID NO: 18 when DNA construct comprises a TIR of nucleotide sequence of SEQ ID NO: 20.
It appears that applicant inadvertently omitted the word “the” before “DNA construct). Appropriate correction is required.
Sequence Compliance
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 because there are sequences in Figure 2, for example, that do not contain a SEQ ID NO.
37 CFR 1.821 Nucleotide and/or amino acid sequence disclosures in patent applications.
(a) Nucleotide and/or amino acid sequences, as used in §§ 1.821 through 1.825, are interpreted to mean an unbranched sequence of 4 or more amino acids or an unbranched sequence of 10 or more nucleotides. Branched sequences are specifically excluded from this definition. Sequences with fewer than four specifically defined nucleotides or amino acids are specifically excluded from this section.
A complete response to this office action must correct the defects cited above regarding compliance with the sequence rules and a response to the action on the merits which follows.
The aforementioned instance of failure to comply is not intended as an exhaustive list of all such potential failures to comply in the instant application. Applicants are encouraged to thoroughly review the application to ensure that the entire application is in full compliance with all sequence rules. This requirement will not be held in abeyance.
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.
Claims 1-3 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.
Instant claim 1 recites “at least one of the nucleotide sequences of SEQ ID No 20 and 21, wherein a nucleotide sequence of SEQ ID NO 20 and 21 is a TIR sequence”.
It is unclear whether the nucleotide sequence of SEQ ID NO: 20 or 21 is a TIR sequence or if a fragment of SEQ ID NO: 20 or 21 is the TIR sequence given that the claim recites “a” nucleotide sequence of SEQ ID NO: 20 and 21 is a TIR sequence rather than “the” sequence of SEQ ID NO: 20 and 21 is a TIR sequence. The metes and bounds of the claim cannot be clearly ascertained.
Claim 1 also recites that “a” nucleotide sequence of SEQ ID NO: 20 and 21 comprises at least the first 9 nucleotides of the signal peptide encoding sequence. Again, it is unclear whether SEQ ID NOs: 20 and 21 comprise at least the first 9 nucleotides of the signal peptide encoding sequence, or whether a fragment of SEQ ID NOs: 20 and 21 comprise at least the first 9 nucleotides of the signal peptide encoding sequence (the claim recites “a” sequence of SEQ ID NO: 20 and 21 rather than “the” sequence).
It is also unclear whether SEQ ID NOs: 20 and 21 already comprise at least the first 9 nucleotides of the signal peptide encoding sequence or if the sequence is supposed to further comprise at least the first 9 nucleotides of the signal peptide encoding sequence.
Additionally, claim 3 recites that the nucleotide sequence that encodes the signal peptide comprises “a” nucleotide sequence of SEQ ID NO: 18 and therefore it is unclear whether the nucleotide sequence that encodes the signal peptide comprises a fragment of SEQ ID NO: 18 (a sequence of SEQ ID NO: 18) or if the nucleotide sequence that encodes the signal peptide comprises the sequence of SEQ ID NO: 18.
Additionally, claim 3 recites that the nucleotide sequence that encodes the signal peptide comprises “a” nucleotide sequence of SEQ ID NO: 18 “when” DNA construct comprises a TIR of nucleotide sequence of SEQ ID NO: 20.
The metes and bounds of the terminology “when” are not definite because the claim does not require a timeframe for this to occur. It appears that applicant intends for the claim to recite “The DNA construct of claim 1 or 2, wherein the DNA construct comprises the sequence of SEQ ID NO: 20 and wherein the nucleotide sequence that encodes the signal peptide comprises the nucleotide sequence of SEQ ID NO: 18”.
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 1-3 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.
Claim 1 recites “a sequence that encodes a signal peptide”, which is a genus of sequences that have not been adequately described in the specification. As the specification discloses that each time a different signal peptide is used, a different TIR is generated, the specification does not adequately describe the instantly recited genus of any sequence encoding any signal peptide, wherein any sequence of SEQ ID NO: 20 or 21 comprises at least the first 9 nucleotides of the signal peptide encoding sequence.
What does spec disclose?
The sequences encoding signal peptides that function within the instant construct as claimed of the instant specification are not representative of the entire claimed genus.
The specification discloses SEQ ID NO: 18 as the nucleotide sequence encoding the PelB signal peptide that functions in the instant construct, which is not representative of the entire claimed genus.
Signal peptides are not conserved in primary sequence and therefore there are many possible sequences that could function as signal peptides. The function depends on the downstream protein sequence, distance from the N-terminus, and translation kinetics, for example. The activity is specific to the native protein and the specific sequence of the signal peptide.
The instant claims encompass nucleotide sequences encoding structurally diverse signal-peptide amino acid sequences. Simple knowledge of the genetic code does not identify the boundaries of the claimed genus. The TIR sequence is inextricably linked to the polypeptide to be produced, although the instant claims do not recite the host strain, signal peptide sequence, or Certolizumab sequence that is necessary to function as claimed.
Claim 3 adequately defines the sequences but is conditional for “when” the construct comprises SEQ ID NO: 20.
The specification describes in Figure 9 a specific expression vector E111 that resulted in higher yields of Certolizumab when compared with E83, which is not representative of the entire claimed genus.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing.
For example, Freudl et al. (Microb Cell Fact (2018) 17:52, 1-10) teach: he secretion of biotechnologically or pharmaceutically relevant recombinant proteins into the culture supernatant of a bacterial expression host greatly facilitates their downstream processing and significantly reduces the production costs. The first step during the secretion of a desired target protein into the growth medium is its transport across the cytoplasmic membrane. In bacteria, two major export pathways, the general secretion or Sec pathway and the twin arginine translocation or Tat pathway, exist for the transport of proteins across the plasma membrane. The routing into one of these alternative protein export systems requires the fusion of a Sec- or Tat-specific signal peptide to the amino-terminal end of the desired target protein. Since signal peptides, besides being required for the targeting to and membrane translocation by the respective protein translocases, also have additional influences on the biosynthesis, the folding kinetics, and the stability of the respective target proteins, it is not possible so far to predict in advance which signal peptide will perform best in the context of a given target protein and a given bacterial expression host(abstract).
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of species for nucleotide sequences that encode signal peptides in combination with SEQ ID NO 20 or 21 in a DNA construct that expresses any recombinant protein as claimed. Thus, one skilled in the art would be led to conclude that Applicant was not in possession of the claimed invention at the time the application was filed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached M-F 8:00am-6:00pm.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636
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