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
Election/Restrictions
Applicant's election without traverse of the species elections for claims 2, 3 and 10 in the reply filed on 11/05/2025 is acknowledged. After further consideration, the species election requirement is withdrawn and limitations in the claims will be examined.
Status of the Application
Claims 1-13, 15 and 23-27 are pending. Claims 1-13, 15, 23, 24, 26 and 27 are currently under examination. Claim 25 is withdrawn and being drawn to a non-elected species.
Information Disclosure Statement
The submission of the Information Disclosure Statement on 09/06/2022 is in compliance with 37 CFR 1.97. The information disclosure statement has been considered by the examiner and signed copies have been placed in the file.
Claim Objections
Claims 4 and 15 are objected to because of the following informalities: The claim recites the word “form” in the second sentence and should recite “from”. Appropriate correction is required.
Claim 15 recites “1and” which appears to be a typographical error and would need a space between the number and word. 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.
Claims 2, 3 and 12 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.
Claim 2 recites “forming the stem region of the adaptors of the clDNA” and lacks antecedent basis because claim 1 does not recite adapters. For examination purposes, the modified nucleotides can be in the stem region which is within the double stranded DNA as recited in claim 1.
Claim 3 recites “within the strand region defined by the nucleotides at positions 1 to 5 with respect the last nucleotide forming the loop” and “within the strand region defined by the nucleotides 1 to 10 with respect to the last nucleotide forming part of the DNA sequence of interest”. These limitations are indefinite because it is unclear which strand of the double stranded DNA sequence would represent positions 1 to 5 or 1 to 10. It is further unclear which end would be position 1, either the 5’ or the 3’ end of each strand. For examination purposes, the modified nucleotides can be in the stem region which is within the double stranded DNA as recited in claim 1.
Claims 2 and 3 recite the limitation “or, alternatively,” and is indefinite because the recitation of “or” already indicates the clDNA can comprise the last option listed for the modification and thus the term “alternatively” is redundant. Also the claim could be interpreted such as the clDNA has the first two options or “alternatively” just the last option. For examination, the claims are interpreted such that the clDNA can have any one of the modification options.
Claim 12 lacks antecedent basis because it recites “the sequence of interest” and depends from claim 1 which recites “the DNA sequence of interest”. For examination purposes, claim 12 is interpreted as “the DNA sequence of interest”.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 26 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 26 fails to further limit claim 25 from which it depends. Claim 25 is drawn to a viral vector and claim 26 is drawn to a non-viral vector which is not a type of viral vector and therefore broadens the scope instead of limiting the claim to a type of viral vector. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 –
(a)(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.
Claim(s) 1-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Metzker et al. (WO 2015/157747 of record cited on IDS filed 09/06/2022).
Metzker et al. teach a closed linear DNA molecule comprising hairpin loops at each end of a double stranded sequence (00012). Metzker et al. teach the double stranded sequence (stem region) can comprise one or more modified nucleotides such as LNA and phosphorothioate (00052). The limitation of claim 8 reciting thiophosphate is defined in the specification as a thiophosphate is known as phosphorothioate, so the limitation is taught by the prior art.
Thus Metzker et al. anticipates the instant claims.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Serantes et al. (US 2020/03262403) and Metzker et al. (WO 2015/157747 of record cited on IDS filed 09/06/2022).
Regarding claims 1 and 9-11, Serantes et al. teach double stranded DNA molecules with hairpin adapter sequences attached at the ends (0038). Serantes et al. teach the hairpin adapter sequences comprising a primase/polymerase recognition sequence (0055). Serantes et al. teach restriction sites on each side of the double stranded DNA for use in attaching the hairpin adapter sequences (0049 and 0085).
Serantes et al. do not teach the double stranded DNA stem region comprises modified nucleotides.
Regarding claim 1-8, Metzker et al. teach a closed linear DNA molecule comprising hairpin loops at each end of a double stranded sequence (00012) wherein the double stranded sequence can comprise one or more modified nucleotides such as LNA and phosphorothioate (00052). The limitation of claim 8 reciting thiophosphate is defined in the specification as the thiophosphate is also known as phosphorothioate, so the limitation is taught by the prior art.
It would have been obvious to modify the double stranded sequence of Serantes et al. using the known modified nucleotides taught by Metzker et al. to increase stability of the closed linear DNA.
Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed.
Claims 1-8, 12, 13, 15, 23, 24 and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Heinrich et al. ("Linear closed mini DNA generated by the prokaryotic cleaving-joining enzyme TelN is functional in mammalian cells." Journal of molecular medicine 80.10 (2002): 648-654 of record cited on IDS filed 09/09/2022) and Metzker et al. (WO 2015/157747 of record cited on IDS filed 09/06/2022).
Regarding claim 1, Heinrich et al. teach a linear closed DNA comprising hairpin loops and comprising a DNA sequence (Fig. 2B).
Regarding claims 13, 15, 23, 24 and 26, Heinrich et al. teach the DNA sequence comprised in a vector backbone for expression and was delivered to a cell using a lipofectamine (see page 651).
Regarding claims 12, Heinrich et al. teach the closed linear DNA comprises inverted terminal repeats at the ends of the DNA sequence (see Fig. 1 and page 650).
Heinrich et al. do not teach the DNA sequence is modified.
Regarding claim 1-8, Metzker et al. teach a closed linear DNA molecule comprising hairpin loops at each end of a double stranded sequence (00012) wherein the double stranded sequence can comprise one or more modified nucleotides such as LNA and phosphorothioate (00052). The limitation of claim 8 reciting thiophosphate is defined in the specification as the thiophosphate is also known as phosphorothioate, so the limitation is taught by the prior art.
It would have been obvious to modify the double stranded sequence of Heinrich et al. using the known modified nucleotides taught by Metzker et al. to increase stability of the DNA.
Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed.
Claims 1-8, 13, 15, 23, 24, 26 and 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Walters et al. ("Comparative analysis of enzymatically produced novel linear DNA constructs with plasmids for use as DNA vaccines." Gene therapy 21.7 (2014): 645-652) and Metzker et al. (WO 2015/157747 of record cited on IDS filed 09/06/2022).
Regarding claim 1, Walters et al. teach a linear closed DNA comprising hairpin loops and comprising a DNA sequence (Fig. 1B).
Regarding claims 13, 15, 24 and 26-27, Walters et al. teach the DNA sequence comprised in a vector backbone for expression and a polycationic complex (PEI) carrier (see page 647).
Walters et al. do not teach the DNA sequence is modified.
Regarding claim 1-8, Metzker et al. teach a closed linear DNA molecule comprising hairpin loops at each end of a double stranded sequence (00012) wherein the double stranded sequence can comprise one or more modified nucleotides such as LNA and phosphorothioate (00052). The limitation of claim 8 reciting thiophosphate is defined in the specification as the thiophosphate is also known as phosphorothioate, so the limitation is taught by the prior art.
It would have been obvious to modify the double stranded sequence of Heinrich et al. using the known modified nucleotides taught by Metzker et al. to increase stability of the DNA.
Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Written Description
Claims 1-13, 15, 23, 24, 26 and 27 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious" and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966; Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial Structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and v. Correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art.
Moreover, the written description requirement for a genus may be satisfied through sufficient description of a representative number of species by “…disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between functional and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.” Thus when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The claims are drawn to a genus of closed linear DNA (clDNA) comprising any sized double stranded DNA sequence and hairpin loop sequences and further comprises any nucleotide modification in any loop or DNA sequence, any sized inverted terminal repeat (ITR), any location of the restriction sites and primase sites in the sequences wherein the clDNA is capable of in vivo expression of any gene of interest.
The specification describes several clDNA with specific loop sequences (Table 3) and containing two modified nucleotides that were capable of showing increased luciferase activity when transfected tin HaCat cells in vitro (Example 2).
When determining whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. The specification describes several clDNA with specific loop sequences (Table 3) and containing two modified nucleotides that were capable of showing increased luciferase activity when transfected into HaCat cells in vitro (Example 2). The genus comprises a vast number of different lengths and modified nucleotide configurations. The specification does not describe the lengths of the clDNA, the type and positions of the modified nucleotides and further the specification and claims do not indicate what distinguishing characteristics are concisely shared by the members of the broad genus of clDNA that would convey to one of skill in the art that these dsRNA represent the entire genus. A review of the specification shows that it provides no description or guidance that would allow one of skill to distinguish the functional species of the recited structural genus from the non-functional members without empirical determination.
Then it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e. other than nucleotide sequence), specific features and functional attributes that would distinguish different members of the claimed genera. In the instant case, the only other identifying characteristics is the ability of a several clDNA, having two modified nucleotides, to increase a luciferase gene expression in cells in vitro. Such functional limitation cannot be the identifying characteristics that represents the claimed diverse genus of molecules given each clDNA would have a different function, depending on the length and nucleotide sequence, for expression of a gene in vivo.
Since the disclosure and the prior art fail to describe the common attributes and characteristics concisely identifying members of the proposed genus, and because the claimed genus is highly variant comprising a vast number of lengths and modified clDNA sequences, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus claimed.
"A sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
Further, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” Ex parte Kubin, 83 USPQ2d 1410, 1417 (Bd. Pat. App. & Int. 2007) citing University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. 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).
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. 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, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618.
Thus the specification and claims lack written description because it is clear that Applicant did not have possession of every type of clDNA with the function of in vivo expression of any gene of interest.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521,222 USPQ 369,372-372 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the entire scope of the claimed invention.
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. See 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);and, 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/forms/. The 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-13, 15, 23, 24, 26 and 27 are provisionally rejected under the judicially created doctrine of double patenting over claims 19 and 25 of co-pending Application No. 17,796,596 (App596). This is a provisional double patenting rejection since the conflicting claims have not yet been patented. Although the conflicting claims are not identical, they are not patentably distinct from each other because the instant claims and the claims of the patent are drawn to patently indistinguishable subject matter. Claims 19 and 25 of App 596 are drawn to a closed linear DNA and is not patentably distinct from the instantly claimed closed linear DNA.
This is a provisional obviousness-type double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly Chong at (571)272-3111. The examiner can normally be reached Monday thru Friday between M-F 8:00am-4:30pm.
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636