DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse of the species “-(CH2-CH2)n where n=1-5” for spacer R3 and the species “solid substrate” for R5 in the reply filed on 7/21/2026 is acknowledged. However, upon further consideration, the species election requirement has been withdrawn.
3. Claims 1-5 are currently pending and under examination.
Claim Rejections - 35 USC § 112
4. 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.
5. Claims 1-5 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.
(1). Claim 1 recites “wherein R1 is -((CH2-CH2-)n)-R5 where n is 1-5, -((CH2-)n)-R5 where n is 1-10, a phosphoramidite, or a combination thereof”. There are multiple issues with this wherein clause. First, when R1 is a “phosphoramidite”, it is not clear whether the phosphorous atom that is necessarily comprised in said “phosphoramidite” refers to the phosphorous atom currently connected to R1 or a separate phosphorous atom. If it refers to a separate phosphorous atom comprised in said “phosphoramidite”, then how is this separate phosphorous atom connected with the phosphorous atom that is currently connected to R1? If the phosphorous atom that is necessarily comprised in said “phosphoramidite” refers to the phosphorous atom currently connected to R1, then applicant should correct the structure in claim 1 to have the phosphorous atom within said “phosphoramidite” (i.e., R1 would be N,N-diisopropylamino (instead of “a phosphoramidite”) if the branching phosphoramidite monomer as shown in Figure 8 (see “Compound 6”) is used to construct the comb-like branching molecule of claim 1).
Second, when R1 is “-((CH2-CH2-)n)-R5 where n is 1-5” or “-((CH2-)n)-R5 where n is 1-10”, a carbon atom from the R1 group is directly connected to a phosphorous atom. However, when a branching phosphoramidite monomer like the one as shown in Figure 8 (see “Compound 6”) is used to construct the comb-like branching molecule of claim 1, a hydroxyl group would usually react with the phosphoramidite to result in a structure having an oxygen atom connected to the phosphorous atom from the phosphoramidite (see page 8, line 24 – page 9, line 8 of the amended specification filed on 1/22/2025 or paragraph [0035] of the published application (US 2023/0295717 A1)).
Third, regarding the recitation “a combination thereof”, it is unclear how could R1 be a combination of “a phosphoramidite” and “-((CH2-CH2-)n)-R5 where n is 1-5”, or a combination of “a phosphoramidite” and “-((CH2-)n)-R5 where n is 1-10”. In addition, when R1 is a combination of “-((CH2-CH2-)n)-R5 where n is 1-5” and “-((CH2-)n)-R5 where n is 1-10”, how these two groups are connected to the phosphorous atom in the structure shown in claim 1? Are there two “R5” (i.e., one R5 from “-((CH2-CH2-)n)-R5 where n is 1-5” and another R5 from “-((CH2-)n)-R5 where n is 1-10”) within the R1 group? If so, it is unclear how it would be possible to have two solid substrates within a single molecule when R5 is a solid substrate.
Claims 2-5, each of which depends from claim 1, are also rejected for the same reasons as discussed above.
(2). Claim 2 recites “wherein the spacer (R3) is -(CH2-CH2)n where n is 1-5, -(CH2-)n where n is 1-10, a phosphoramidite, an oligonucleotide, or a combination thereof”. There are multiple issues with this wherein clause. First, when R3 is a “phosphoramidite”, it is not clear whether the phosphorous atom that is necessarily comprised in said “phosphoramidite” refers to the phosphorous atom currently connected to R3 or a separate phosphorous atom. If it refers to a separate phosphorous atom comprised in said “phosphoramidite”, then how is this separate phosphorous atom connected with the phosphorous atom that is currently connected to R3? If the phosphorous atom that is necessarily comprised in said “phosphoramidite” refers to the phosphorous atom currently connected to R3, then applicant should correct the structure in claim 1 to have the phosphorous atom within said “phosphoramidite”.
Second, when R3 is “-(CH2-CH2)n where n is 1-5” or “-(CH2-)n where n is 1-10”, a carbon atom from the R3 group is directly connected to a phosphorous atom. However, when a branching phosphoramidite monomer like the one as shown in Figure 8 (see “Compound 6”) is used to construct the comb-like branching molecule of claim 1, a hydroxyl group would usually react with the phosphoramidite to result in a structure having an oxygen atom connected to the phosphorous atom from the phosphoramidite (see page 8, line 24 – page 9, line 8 of the amended specification filed on 1/22/2025 or paragraph [0035] of the published application (US 2023/0295717 A1)).
Third, regarding the recitation “a combination thereof”, it is unclear how could R3 be a combination of “a phosphoramidite” and “-(CH2-CH2)n where n is 1-5”, or a combination of “a phosphoramidite” and “-(CH2-)n where n is 1-10”.
Conclusion
6. No claim is currently allowed. However, once the 112 issues (as discussed above) are resolved, claims 1-5 will be allowable. The prior art does not teach or reasonably suggest the comb-like branching molecule of instant claim 1. Specifically, Iyer et al. (US 5,916,750), regarded as the closest prior art, disclose a comb-like branching molecule (see Figure 1B) constructed by using the asymmetric amidite “structure II” (see column 10, lines 7-34). However, the comb-like branching molecule disclosed by Iyer et al. is structurally different from the comb-like branching molecule of instant claim 1.
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/KAIJIANG ZHANG/Primary Examiner, Art Unit 1684
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