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 with traverse of Group I, claim 1 and 3-34 in the reply filed on 04/24/2025 is acknowledged. Applicant traversal is on the grounds that there is not serious search burden between Groups I and II. After further consideration Groups I and II will be examined together.
Group III was not traversed and thus the Requirement for Restriction for Group III is made FINAL.
Status of the Application
Claims 1-39 are pending and are currently under examination.
Claims 1-34 are examined and claims 35-39 are withdrawn as being drawn to a non-elected group.
Specification
The disclosure is objected to because Tables 1-13 are in small font and therefore some of the nucleotides and annotations are unclear and cannot be read correctly. Appropriate correction is necessary.
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 5 and 6 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 5 and 6 recite "wherein each linking group that contains a non-nucleotide structure independently represents a group represented by the following formula…". This limitation is unclear because the claims list what appears to be alternatives along with the formula such that the linking group can be the recited formula, a group selected from XIII1 to XIII11, a ribonucleoside group, a deoxyribonucleoside group, or a C2-50 alkylene group which is unsubstituted or substituted. The claims are interpreted for examination purposes as one of these alternatives.
The claims also recite “each group that contains a non-nucleotide structure independently represents a group represented by the following formula..”. It is unclear if that means each linking group L, Lz and Ly can contain any one of the alternatives listed or each of the linking groups are the same and represented as claimed. The claims are interpreted ad each linking group can be different.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3, 4, 9-12, 14, 15 and 28-34 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by McSwiggen et al. (US Application No. 20070032441).
The claims are drawn to a single-stranded oligonucleotide represented by the following formula (I): [Xz-L x]m-X-L-Y-[Ly-Yz]n, wherein X is represented by Xb-Xa, 4-40 or 1-40 nucleotides respectively, wherein Xb bonds to Xa at the 5’end and Y bonds to Xa on the 3’ side, the sequence X contains an antisense sequence capable of hybridizing with a target RNA, wherein at least four contiguous nucleotides are recognized by RNase H, wherein Xb and Y hybridize. A further limitation of the claim recites the alternative “m represents 0 or 1” and when m represents 0, n represents 0 or 1.
The claims are interpreted at a minimum as a single stranded oligonucleotide represented by:
X – L - Y,
[Xz-Lx]m and [Ly-Yz]n are not part of the structure since m can be 0 and n can be 0
X and Y hybridize (which is interpreted as hybridize to each other)
L is a linker and it is either a non-nucleotide structure or a group represented by the formula in Claims 1 and 2.
The limitations above describes the structure as capable of forming a double stranded molecule wherein X contains nucleotides complementary to nucleic acid sequences of Y, thus forming a double stranded oligonucleotide connected by a linker.
Thus for prior art purposes, the claimed oligonucleotide forms a double stranded structure as described above and any prior art with the same structure of X – L – Y wherein L can be a non-nucleotide linker would anticipate the instant claims.
Regarding claims 1, 3, 4, 7, 15, McSwiggen et al. teach a single stranded molecule wherein one strand is an antisense strand and the other is a sense strand that are connected to a linker molecule that can be a polynucleotide linker (0032) wherein the single stranded nucleotide can be used in methods for modulating gene expression (0002). McSwiggen et al. teach each strand can be from 19-29 nucleotides in length (0043-0044). McSwiggen et al. further describes the structure as a linear hairpin molecule wherein loop is 3 to 10 nucleotides in length (0143) wherein the linker binds bonds to X on the 5’ side (Fig. 62). McSwiggen et al. teach the loop can be a non-nucleotide linker (0112).
Regarding claims 9-12, 14, 33, McSwiggen et al. teach each strand of the molecule can be modified extensively to enhance stability by modification with nuclease resistant groups, for example sugar modifications, 2'-amino, 2'-C-allyl, 2'-fluoro, 2'-O-methyl, 2'-H, deoxyribonucleotides and chemical modifications of oligonucleotide internucleotide linkages with phosphorothioate, phosphorothioate, and/or 5'-methylphosphonate linkages improves stability (see 0019-0020, 0139-0141).
Regarding claims 28-32 and 34, McSwiggen et al. teach the oligonucleotide can be in pharmaceutical compositions and teach conjugates and/or complexes that can be used “to facilitate delivery of siNA molecules into a biological system, such as a cell. The conjugates and complexes provided by the instant invention can impart therapeutic activity by transferring therapeutic compounds across cellular membranes, altering the pharmacokinetics, and/or modulating the localization of nucleic acid molecules of the invention. The present invention encompasses the design and synthesis of novel conjugates and complexes for the delivery of molecules, including, but not limited to, small molecules, lipids, cholesterol, phospholipids, nucleosides, nucleotides, nucleic acids, antibodies, toxins, negatively charged polymers and other polymers, for example, proteins, peptides, hormones, carbohydrates, polyethylene glycols, or polyamines, across cellular membranes. In general, the transporters described are designed to be used either individually or as part of a multi-component system, with or without degradable linkers. McSwiggen et al. teach using the siRNA to target specific cell types such as targeting the asialoglycoprotein receptor (see 0770) and teach a sugar conjugate N-acetyl-galactosamine (0552). McSwiggen et al. teach methods of design and synthesis of said molecules (see 0808-0813).
Thus McSwiggen 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 2, 8 and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over McSwiggen et al. (US Application No. 20070032441) and ) and Yakota et al. (US 20140302603).
McSwiggen et al. is relied upon as above. McSwiggen et al. do not specifically teach “wherein at least one antisense sequence contains at least four contiguous nucleotides recognized by RNase H”.
Regarding claims 2, 8 and 13 having the limitation of “contains at least four contiguous nucleotides recognized by RNase H”, the specification describes RNase H can recognize a double strand in which at least one of the base moiety, phosphodiester bond moiety or sugar moiety of at least one of DNA and RNA has been modified [0025]. McSwiggen et al. teach base, sugar or phosphodiester modification can be from 5-100% of each strand and thus it would encompass having at least four contiguous nucleotides recognized by RNase H.
Yakota et al. teach a nucleotide strand having at least four or more contiguous nucleotide recognized by RNase H is advantageous to promote cleavage (0129). Thus it would have been obvious to one of ordinary skill in the art to incorporate at least 4 contiguous nucleotides into the strands taught by McSwiggen et al. that are recognized by RNase H to promote cleavage.
Therefore it would have been obvious to use the oligonucleotide structure of McSwiggen et al. and incorporate four contiguous nucleotides recognized by RNase H, wherein the nucleotides are not all deoxyribonucleotides, comprises modified nucleotides and can be a multimeric composition as taught above to target the same or different genes for inhibition of gene expression.
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 1-34 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 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 claims are drawn to a genus of a single-stranded oligonucleotides represented by the following formula (I): [Xz-L x]m-X-L-Y-[Ly-Yz]n, wherein X is represented by X, Xz, Yand Yz are 7-100 nucleotides, wherein L is a linker represented by a non-nucleotide or any group as in claims 1, 2, 5 and 6.
The specification describes single stranded oligonucleotides 13-44 in length in Tables 1-13 with denotations for X, L and Y and describes these oligonucleotides can hybridize to several target RNAs, such as PTEN and ApoB, and inhibition of gene expression in HuH-7 cells in vitro (Example 3).The specification only appears to represent the structure X-L-Y and not the claimed structure of [Xz-L x]m-X-L-Y-[Ly-Yz]n wherein m and n can be 1.
The specification and claims do not indicate any distinguishing characteristics of these oligonucleotide in the specification that is concisely shared by the members of the broad genus of oligonucleotides claimed that would convey to one of skill in the art that this oligonucleotide represents the entire genus. The genus is broad comprising multiple sizes of antisense and sense strands of 7-100 nucleotides represented by X, Xz, Y and Yz and a broad genus of linkers represented by L and Lx and Ly.
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, particularly having the claimed structure of [Xz-L x]m-X-L-Y-[Ly-Yz]n wherein m and n can be 0 or 1.
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 specification does not describe a representative number of species of the genus oligonucleotides as claimed with the functional characteristics of inhibiting expression of any coronavirus genome.
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 sizes of each individual group within the single stranded oligonucleotide, 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.
“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).
"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).
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 one of skill at the time of the invention could not have concluded that Applicant was in possession of the genus of the single-stranded oligonucleotide as claimed.
Double Patenting-Statutory
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claim 1-34 is/are rejected under 35 U.S.C. 101 as claiming the same invention as that of claim 1-34 of prior U.S. Patent No. 11,572,558. This is a statutory double patenting rejection.
The instant claims and Patent 11,571,558 are drawn to a single-stranded oligonucleotide represented by the formula [Xz-L x]m-X-L-Y-[Ly-Yz]n.
Claims Free of the Prior Art
Claims 16-27 are not anticipated or made obvious by the prior art. The closest prior art is Hamasaki et al. (of record IDS 02/01/2023) who teach dumbbell RNA sequences comprising two complementary sequences attached via a linker but do not teach the single-stranded oligonucleotide having three linkers attaching two sets of complementary antisense and sense regions wherein the strands are 7-100 and 4-100 nucleotides in length or structures wherein m is 0 and n is 1 or wherein m is 1 and n is O, leaving overhang regions (see instant drawings Figs. 1-6). The prior art does not teach it would have been obvious to make the claimed structures.
Conclusion
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.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636
Prosecution Insights