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 the Claims
Claims 1, 3-18, 21, 27, 30-31 and 35-39 are pending. Claims 1, 4-10, 14-18, 21, 27, 30-31 and 35-39 are the subject of this FINAL Office Action. Claims 3 and 11-13 are withdrawn.
Election/Restrictions
Applicant’s election without traverse of the species of (1) sequencing synthesis, (2) solution-phase reaction, (3) Duplase polymerase and (4) template of claim 10 in the reply filed on 02/25/2025 is acknowledged. The elections of (1) and (3) are withdrawn.
Claims 3 and 11-13 are withdrawn.
Claim Interpretations - Maintained
Applicants provide the following examples of “polymerase that requires no more than 7 base pairings to extend said single-stranded primer”:
In some cases, modified 9°N™ DNA polymerases, which are capable of extending a single-stranded primer on a solid surface using a reversible terminator as the source of new base, are used. In some cases, the oligo serves as both the primer and the template. In some cases, such a modified 9°NTM DNA polymerase can be referred to as a Duplase (available at Centrillion Technologies, Palo Alto, CA). Duplases may only require hybridization of two bases for extension (FIG. 3). For example, Duplase-1 (also referred to as CENTI, see US20160355541) can efficiently incorporate reversible terminators along a double-stranded DNA substrate in reaction times as short as one minute when nucleotide concentrations are as low as 2 μMin solution. Longer extension times and higher nucleotide concentrations may be required for extensions of single-stranded oligos
(Spec., para. 0065). Although this is not an explicit definition, yet the Examiner uses these few disclosed species to fill in the meaning of the functional language. In other words, “polymerase that requires no more than 7 base pairings to extend said single-stranded primer” means any modified 9°N™ DNA polymerases.
The specification and claim 21 seem to indicate that modified MMLV reverse transcriptases, such as Superscript IV (Thermo Fisher) and SMARTScribe (Clontech) may also be considered “polymerase [that] requires no more than 7 base pairings to extend said single-stranded primer.” However, this reads on random hexamer/primer RT (see e.g. US 5935818 (“. . . RNA was reverse-transcribed into cDNA using random hexamer primers (Gibco-BRL) and Superscript II reverse transcriptase . . . “)).
Response to Arguments
The interpretations above are maintained. Curiously, Applicants argue that a skilled artisan would have recognized that the claim language of “polymerase [that] requires no more than 7 base pairings to extend said single-stranded primer” encompasses a “vast majority” of modified polymerases that will not perform this claimed function. Specifically,
a person of skill in the art would appreciate that there are countless methods of modifying a polymerase enzyme, the vast majority of which would not result in a "polymerase that requires no more than 7 base pairings to extend said single-stranded primer." For example, a POSA would consider that a polymerase enzyme can be modified using any types of modifications known in the art (e.g., insertions, deletions, and/or mutations at one or more residues) in order to achieve a desired protein engineering result (e.g., to induce a point mutation, domain swapping, or to generate polymerases with any altered activity or desired functionality)
(Reply, pg. 8). In other words, Applicants seem to admit their claimed “polymerase [that] requires no more than 7 base pairings to extend said single-stranded primer” is not enabled for its full scope.
Beyond this seeming admission as to enablement, Applicants still cannot provide a core polymerase structure that meets their functional language. In light of this failure, and the disclosure of a couple examples, the Examiner finds that the claim interpretation is warranted. It is Applicants’ duty to clarify the claims, especially here with Applicants’ choice of functional language. See In re Am. Acad. of Sci. Tech Ctr, 367 F.3d at 1364 (“Our mandate is to give claims their broadest reasonable interpretation.”); In re Zletz, 893 F.2d 319, 322 (Fed. Cir. 1989) (“An essential purpose of patent examination is to fashion claims that are precise, clear, correct, and unambiguous. Only in this way can uncertainties of claim scope be removed, as much as possible, during the administrative process.”).
Claim Rejections - 35 USC § 112- Indefiniteness- Maintained
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.
Claims 14 and 16 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 pre-AIA the applicant regards as the invention.
Claims 14 and 16 make no sense because a primer cannot be any less than 4 bases. See e.g. Baran et al, Studies on the minimal lengths required for DNA primers to be extended by the Tetrahymena telomerase: implications for primer positioning by the enzyme, Nucleic Acids Res. 2002 Dec 15;30(24):5570–5578. doi: 10.1093/nar/gkf676. For example, a one-base primer is no such thing; it is a base. There has never been a one-base primer.
Response to Arguments
The rejection above is maintained. Applicants argue that “none of claims 14 and 16, nor any claim upon which they depend, recites a primer of fewer than 4 bases” (Reply, pg. 9). Applicants have missed the forest for the trees. Claim 1 recites “providing a single-stranded primer comprising a free 3' end . . . extending said single-stranded primer . . . by [a] . . . polymerase [that] requires no more than 7 base pairings to extend.” This encompasses a primer with no more than 7 base pairings with a target. Claims 8, 14 and 16 make this point even more explicit: “hybridizing a hybridization site on said single-stranded primer with a template, wherein said hybridization site is at said 3' end and comprises no more than 7 bases” (claim 8) and “comprises 1, 2, 3, 4, 5, 6 or 7 bases” (claims 14 and 16). Applicants claim language clearly encompasses a primer that only hybridizes at “1, 2, 3, 4, 5, 6 or 7 bases.” Thus, Applicants’ arguments fall flat.
Claim Rejections - 35 USC § 102- Maintained
The following is a quotation of the appropriate paragraphs of 35 U.S.C. § 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 4-10, 14-18, 21, 27, 30-31 and 35-39 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by JU (US20150080232).
As to claims 1, 4, 21 and 30, JU teaches a method of synthesizing nucleic acids using a primer (Figs. 1, 4, 23), dNTPs and a polymerase that requires no more than 7 base pairings to extend said single-stranded primer (9° N polymerase or a variant thereof; paras. 0107, 0232 and claim 29).
As to claims 1 and 5-7 and 31, JU teaches reversible ddNTP terminator, removing 3’ terminator, cleaving and repeating (Fig. 1).
As to claims 8-10, 14 and 16, Figure one shows a 4-base primer on a template, and can be a hairpin (Fig. 4).
As to claim 15, this merely recites a result achieved by using the claimed invention; thus, same steps, same results.
As to claims 17-18, extension occurs at 50-75C (para. 0218, for example).
Response to Arguments
The rejection above is maintained. Applicants argue that JU’s 9° N polymerase or a variant thereof is never disclosed as that requiring no more than 7 base pairings to extend said single-stranded primer. However, “[w]here, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product.” In re Best, 562 F.2d 1252, 1255 (CCPA 1977). In fact,
[I]t is elementary that the mere recitation of a newly discovered function or property, inherently possessed by things in the prior art, does not cause a claim drawn to those things to distinguish over the prior art. Additionally, where the Patent Office has reason to believe that a functional limitation asserted to be critical for establishing novelty in the claimed subject matter may, in fact, be an inherent characteristic of the prior art, it possesses the authority to require the applicant to prove that the subject matter shown to be in the prior art does not possess the characteristic relied on. [In re Swinehart, 439 F.2d 210, 58 CCPA 1027, 169 USPQ 226 (1971)].
[ . . . ]
Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. See In re Ludtke, supra. Whether the rejection is based on ‘inherency’ under 35 U.S.C. § 102, on ‘prima facie obviousness' under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. See In re Brown, 459 F.2d 531, 59 CCPA 1036, 173 USPQ 685 (1972).
In re Best, 562 F.2d 1252, 1254–55 (CCPA 1977) (footnote omitted).
Duplase may be an example, but an example does not define a functional limitation. The Federal Circuit has repeatedly reminded stakeholders that it “is improper to ‘confin[e] the claims to th[e] embodiments’ found in the specification.” In re Trans Texas Holdings Corp., 498 F.3d 1290, 1299 (Fed. Cir. 2007); see also Teleflex, Inc. v. Ficosa N. Am. Corp., 299 F.3d 1313, 1327–28 (Fed. Cir. 2002) (The CAFC has repeatedly “‘cautioned against limiting the claimed invention to preferred embodiments or specific examples in the specification.’”) (quoting Comark Communications, Inc. v. Harris Corp., 156 F.3d 1182, 1186 (Fed.Cir.1998) (quoting Texas Instruments, Inc. v. United States Int'l Trade Comm'n, 805 F.2d 1558, 1563 (Fed.Cir.1986))). The “PTO applies to verbiage of the proposed claims the broadest reasonable meaning of the words in their ordinary usage as they would be understood by one of ordinary skill in the art, taking into account whatever enlightenment by way of definitions or otherwise that may be afforded by the written description contained in applicant’s specification.” In re Morris, 127 F.3d 1048, 1054 (Fed. Cir. 1997). “Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read
into a claim when the claim language is broader than the embodiment.” Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875 (Fed. Cir. 2004). Here, there is no suggestion in the intrinsic record to limit the very broad functional language to any specific examples in the specification. See In re Morris, 127 F.3d 1048, 1054-56 (Fed. Cir. 1997) (“Absent an express definition in their specification, the fact that appellants can point to definitions or usages that conform to their interpretation does not make the PTO’s definition unreasonable when the PTO can point to other sources that support its interpretation.”); see also In re Self, 671 F.2d 1344, 1348 (CCPA 1982) (limitations not appearing in the claims cannot be relied upon for patentability).
The rejections are maintained.
As to claims 37-39, cleavage occurs after ddNTP incorporation (Fig. 1).
As to claims 27 and 35-36, the incorporated base can be uracil (e.g. para. 0006).
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Aaron Priest whose telephone number is (571)270-1095. The examiner can normally be reached 8am-6pm.
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, Gary Benzion can be reached at (571) 272-0782. 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.
/AARON A PRIEST/ Primary Examiner, Art Unit 1681
Prosecution Insights