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 Application/Amendment/Claims
Applicant's response filed 02/23/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 10/27/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
With entry of the amendment filed on 02/23/2026, claims 36, 51-56, 68 and 69 are pending.
Withdrawn Rejections
Claim Rejections - 35 USC § 103
The rejection of claims 36, 51-56, 68 and 69 under 35 U.S.C. 103 as being unpatentable over Adams et al. ("Glycogenosis type II: a juvenile‐specific mutation with an unusual splicing pattern and a shared mutation in African Americans." Human mutation 10.2 (1997): 128-134), Kroos et al. (Update of the Pompe Disease Mutation Database with 107 Sequence Variants and a Format for Severity Rating HUMAN MUTATION, Mutation in Brief #1006, 29:E13-E26, 2008), Wood et al. (US 20180334673) and Zhang et al. ((2005). Antisense Technology. In: Curiel, D.T., Douglas, J.T. (eds) Cancer Gene Therapy. Contemporary Cancer Research. Humana Press. Pg 35-49) is withdrawn in response to the Affidavit filed 02/23/2026.
Response to Declaration
The declaration filed on 02/23/2026 under 37 CFR 1.132 states that the claimed sequences having SEQ ID No. 1590-1594 do not bind to regions to exclude exon 6 as in the 103 rejection. The declaration states SEQ ID Nos. 1590-1591 target aberrant splice produces in GAA intron 15. SEQ ID No. 1592 target aberrant splice produces in GAA exon 8. SEQ ID No. 1593 target aberrant splice produces in GAA intron 10 and SEQ ID No. 1594 target aberrant splice produces in GAA intron 12. Because Applicant has declared that the sequences do not target aberrant splice sites in intron 6, the 103 rejection drawn to this intron is moot as it would not be obvious to target intron 6 using the claimed sequences.
New Claim Rejections
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 36, 51-56, 68 and 69 under 35 U.S.C. 103 are rejected as being unpatentable over Kroos et al. (Update of the Pompe Disease Mutation Database with 107 Sequence Variants and a Format for Severity Rating HUMAN MUTATION, Mutation in Brief #1006, 29:E13-E26, 2008 of record cited on 892 mailed 10/27/2025), Bergsma et al. ("Identification and Characterization of Aberrant GAA Pre‐m RNA Splicing in P ompe Disease Using a Generic Approach." Human Mutation 36.1 (2015): 57-68), Wood et al. (US 20180334673 of record cited on 892 mailed 10/27/2025) and Zhang et al. ((2005). Antisense Technology. In: Curiel, D.T., Douglas, J.T. (eds) Cancer Gene Therapy. Contemporary Cancer Research. Humana Press. Pg 35-49 of record cited on 892 mailed 10/27/2025).
The claims are drawn to antisense oligomeric compound having a length of maximally 30 nucleotides and comprising a sequence selected from the group consisting of SEQ ID NO: 1590- 1594 and sequences having at least 91% identity thereof, wherein at least one of the nucleotides is modified. The declaration states SEQ ID Nos. 1590-1591 target aberrant splice produces in GAA intron 15. SEQ ID No. 1592 target aberrant splice produces in GAA exon 8. SEQ ID No. 1593 target aberrant splice produces in GAA intron 10 and SEQ ID No. 1594 target aberrant splice produces in GAA intron 12.
Kroos et al. teach Pompe disease, also known as glycogen storage disease type II, acid a-glucosidase and acid maltase deficiency (MIM# 232300), is an autosomal recessive lysosomal storage disorder and provides a database of sequence variants of the acid α-glucosidase gene (GAA) which causes Pompe disease (see abstract). Kroos et al. describes the cDNA reference sequence NM_000152.3 and lists the precise position of each nucleotide change in variants of the GAA gene (Table 2). Kroos et al. has identified exons and introns associated with the disease such as exon 8 and introns 10, 12 and 15 (see Tables). This provides evidence that positions of variants in the GAA gene can be identified. Moreover, the complete coding sequences of GAA is known and available as GenBank M34424.1 (retrieved 10/23/2025 NCB1).
Bergsma et al. describes identification and characterization of aberrant GAA splicing in Pompe Disease and identified several exons and intron such as exon 8 and intron 10 (see Table 1 and Table 2). Bergsma et al. concludes that splicing is a promiscuous process in which noisy splicing and leaky wild-type splicing are often present. The implication is that splicing should be amenable to modulation. For example, small molecules targeting splicing factors may present a worthwhile therapeutic strategy to treat genetic diseases caused by splicing variants (see page 67 last para.).
Wood et al. is a patent application that discloses using antisense oligonucleotides for targeting sequences in pre-mRNA and teach sequences may alternatively include those which comprise a mutation in an intron of a human gene that disrupts correct splicing of the pre-mRNA transcribed from the gene. Such mutations may result in a protein with an internal deletion (lacking an exon), which may be non-functional. Oligonucleotides which specifically hybridise to target sequences which comprise a mutation in an intron preferably suppress the exclusion of a subsequent exon during pre-mRNA splicing, resulting in a functional protein which includes the exon. Such oligonucleotides are preferred for inclusion in a molecule of the invention. (0106). Wood et al. teach any therapy that can improve the level of exons that are included is likely to be highly beneficial (0107). Wood et al. teach antisense oligonucleotides can be modified with 2’-O-methyl or comprise a modified base or backbone and teach pharmaceutical compositions comprising said antisense oligonucleotide (0079-0091 and 0112). This meets the limitations of claims 51-56, 68 and 69.
Zhang et al. teach there are well known reliable approaches to select an optimal antisense sequence such as sequence-walking which has yielded good results or computer aided target selection which allows antisense to be designed to target regions of mRNA predicted to be free from intramolecular base pairing (see page 40).
There is a need to solve the problem of the aberrant splicing involved in Pompe disease and given GAA variants in exon 8 and introns 10, 12 and 15 are known in the prior art, there is a finite number of antisense oligonucleotides that can be designed to target this region. Because Bergsma et al. teach the implication is that splicing should be amenable to modulation and suggests small molecules targeting splicing factors may present a worthwhile therapeutic strategy to treat genetic diseases caused by splicing variants, it would have been obvious to try making an antisense oligomer comprising any of SEQ ID Nos. 1590-1594 or sequences having at least 91% identity thereof using known coding sequences of GAA given the methods as taught by Zhang, with a reasonable expectation of success. Wood et al. provides further motivation to target an intron to improve the levels of exons that may be affected by the variant intron.
In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that "obvious to try" was a valid rationale for an obviousness finding, for example, when there is a "design need" or "market demand" and there are a "finite number" of solutions. 550 U.S. at 421 ("The same constricted analysis led the Court of Appeals to conclude, in error, that a patent claim cannot be proved obvious merely by showing that the combination of elements was ‘[o]bvious to try.’ ... When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under §103."). Thus, after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.
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 36, 51-56, 687 and 69 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 antisense oligonucleotides having a length of 30 nucleotides max comprising SEQ ID Nos. 1590-1594 and oligonucleotides having at least 91% identity to said sequences with the function of targeting exons and introns in the GAA gene.
The specification describes oligonucleotides having SEQ ID Nos. 1590-1594. The specification does not describe sequences having at least 91% identity to SEQ ID Nos. 1590-1594 or sequences having a length of 30 nucleotides max comprising SEQ ID Nos. 1590-1594 with the function of targeting exons and introns in the GAA gene.
The specification and claims do not indicate what distinguishing characteristics of the sequences described in the specification that are concisely shared by the members of the broad genus of antisense oligonucleotides. 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.
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 differently sized antisense oligonucleotide 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 antisense oligonucleotide having a length of 30 nucleotides max comprising SEQ ID Nos. 1590-1594 and oligonucleotides having at least 91% identity to said sequences with the function of targeting exons and introns in the GAA gene.
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.
Conclusion
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636