DETAILED ACTION
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 .
Application Status
This action is written in response to applicant’s correspondence received on 6/20/2024. Claims 1-11, 21, 23, 25-26, 29-30, 70, 85, and 87 are pending. Claims 3-11, 21, 23, 25-26, 29-30, and 85 have been amended. Claims 12-20, 22, 24, 27-28, 31-69, 71-84, 86, and 88-131 have been previously cancelled. All pending claims are currently under examination.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
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 25-26, 29-30, 85, and 87 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.
Regarding claim 25, claim 25 depends from claims 23, 21, 6, and ultimately claim 1. Claim 1 is drawn to “RNA” as the pharmaceutical composition. Claim 25 recites “free RNA.” The specification defines “free RNA” as “non-complexed” or “non-formulated” or “non-encapsulated” RNA, for instance unencapsulated with regard to a lipid nanoparticle (page 20, 6th paragraph). Seeing as claim 1 is drawn simply to RNA, and not lipid-encapsulated RNA or “formulated” RNA, it is unclear how the term “free RNA” is meant to limit the claim, as claim 1, and by dependency claim 25, is not drawn to lipid-encapsulated RNA, but instead broadly drawn to “free RNA.” The exact structure/composition being recited in claim 25 is therefore generally unclear.
Claims 26 and 29-30 depend from claim 25 and do not resolve this 112(b) issue and are therefore also rejected.
Regarding claim 26, claim 26 recites “the RNA of the pharmaceutical composition of component B.” Claim 26 depends from claim 25, which recites “the pharmaceutical composition of component B comprises less than 20% free RNA.” Thus, two “RNAs” are recited in claim 25 to be comprised in component B: the “free RNA” and the “RNA” in the composition of component B recited in claim 1. Recitation of “the RNA” in claim 26 is therefore unclear because it lacks proper antecedent basis. It is unclear to which RNA is meant to be about 1000 nucleotides in length (i.e., the “free RNA” or the pharmaceutical composition of claim 1’s RNA). Claims 29-30 depend from claim 26 and do not resolve this 112(b) issue and are therefore also rejected. Furthermore, recitation of “the RNA” in claims 29-30 lack proper antecedent basis for the same reasons given above and are therefore rejected further.
Regarding claim 85, claim 85 recites “a subject” and “the subject in need thereof.” It is unclear if these two phrases refer to the same subject as “the subject in need thereof” as a phrase lacks proper antecedent basis. Furthermore, claim 85 recites “obtained in A) or B1” however, there is no “B1” presently recited in the claim. Thus, recitation of “B1” is unclear in step B and lacks proper antecedent basis.
Regarding claim 87, claim 87 recites obtaining a liquid composition (A) and transferring the liquid to a syringe (B). Claim 87 then recites “obtaining a syringe containing a liquid composition.” It is unclear if two separate syringes are being recited with two separate liquid compositions, or if step C is meant to be the syringe obtained by the product of steps A and B. Furthermore, step D recites “freeze the obtained syringe,” where “the obtained syringe” lacks proper antecedent basis because two separate syringes are recited (steps A and C); it is therefore unclear to which obtained syringe is being referred in step D. Similarly recitation of “the composition contained in the obtained syringe” in step D and “stably storing the obtained syringe” lack proper antecedent basis, as is it unclear to which syringe is being referred (i.e., the syringe in step A or steps C or D).
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.
Claims 6-11, 21, 23, 25-26, 29-30 are 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.
Regarding claim 6, claim 6 depends from claim 1. Claim 1 recites that the inner surface of the syringe barrel and/or syringe plunger stopper is essentially free of silicone oil. However, claim 6 recites that further elements are also silicone free (e.g., the needle adaptor). Thus, claim 6 fails to limit the limitations of claim 1, as claim 6 in fact expands and adds new limitations to the claim regarding different parts of the syringe (e.g., the needle adaptor).
Furthermore, claims 7-11, 21, 23, 25-26, and 29-30 ultimately depend from claim 6 and therefore recite the same limitation-expanding language as that of claim 6 and are therefore also rejected.
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 (i.e., changing from AIA to pre-AIA ) 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.
Claims 1, 3, 5-11, 23, 25, 70, 85, and 87 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ashmead (US 2017/0173267 A1, published 6/22/2017). The rejection of claim 3 is further evidenced by Bajan (Bajan S et al. Cells. 2020 Jan 7;9(1):137).
Regarding claim 1, Ashmead teaches a syringe silicone-free syringe barrel comprising at least one therapeutic (throughout, for instance see claim 1 of Ashmead). The combination of syringe and therapeutic can reasonably be interpreted to be a “kit,” as such a term broadly encompasses the presence of items together. Furthermore, Ashmead teaches that the therapeutic can be RNA interference (i.e., RNA, throughout, see claim 3 of Ashmead).
Regarding claim 3, Ashmead teaches that the therapeutic can be “antisense,” (e.g., see claim 3 of Ashmead). As evidenced by Bajan, “antisense” nucleic acids are single-stranded RNA (or DNA) (page 4, final paragraph). Thus, by teaching “antisense,” Ashmead inherently teaches single-stranded RNA. Furthermore, given that Ashmead teaches “antisense” as a therapeutic, the practitioner could at once envision single-stranded RNA, as antisense inherently means either single-stranded RNA or DNA (Bajan, page 4, final paragraph).
Regarding claim 5, claim 5 merely recites an inherent property of the syringe of claim 1. As such, given that Ashmead teaches the recited syringe to be used with an RNA product, step (iii) of claim 5 is an inherent property of the syringe taught by Ashmead absent evidence to the contrary. Given that the structure of the syringe of Ashmead is identical to that presently recited, it is assumed that the recited characteristics are inherently present in the syringe of Ashmead with regards to step iii (see MPEP 2112, section III, for a discussion on inherent characteristics of identical products).
Regarding claim 6, Ashmead teaches that the inner surface of the syringe barrel is silicon-free (see claim 1 of Ashmead).
Regarding claim 7, Ashmead teaches that the syringe barrel can comprise cyclic olefin copolymer (COP, e.g., paragraph 65).
Regarding claim 8, Ashmead teaches that the syringe barrel can comprise glass (paragraph 65).
Regarding claim 9, Ashmead teaches that such silicon-free syringes can comprise syringe barrels made of glass, which reasonably includes a glass inner surface (i.e., “coating” or top layer, see for instance paragraph 112).
Regarding claim 10, Ashmead teaches that the syringe plunger stopper comprises a thermoplastic elastomer (paragraph 55) or rubber (paragraph 100).
Regarding claim 11, Ashmead teaches that the stopper can comprise a fluoropolymer barrier (paragraph 33). Per the present specification, a fluoropolymer is an example of a compound which reduces gliding force needed for an injection (e.g., page 14, paragraph 7 of present specification). Thus, Ashmead teaches that the stopper comprises a coating/barrier comprising a coating to reduce gliding force by teaching a stopper with fluoropolymer barrier (paragraph 33).
Regarding claim 23, the specification states that “RNA integrity” describes a complete RNA sequence with correct length present in the pharmaceutical. Thus, “RNA integrity” is simply describing an inherent property of the RNA molecule present in, for instance, the syringe. Given that Ashmead teaches the same structure/product of syringe and RNA, absent any evidence to the contrary, it is proper to assume that claim 23 is drawn to inherent characteristics of the syringe/RNA combination already taught by Ashmead (e.g., claims 1 and 3, see MPEP 2112, section III).
Regarding claim 25, as discussed above, claim 25 appears to suffer 112(b) issues, as the term “free RNA” appears to relate to encapsulated or formulated RNA, however, claim 25 depends from claim 1 which does not recite encapsulated or formulated RNA but only “RNA.” For the purposes of this rejection of claim 25, the term “free RNA” in reference to “RNA” is interpreted to mean simply additional RNA molecules other than those in the syringe. In this regard, Ashmead teaches embodiments of the syringe with RNA, where no additional “free RNA” is taught (see claims 1 and 3 of Ashmead). Thus, claims 1 and 3 of the embodiments of Ashmead read on presently recited claim 25.
Regarding claim 70, Ashmead teaches a pre-filled syringe for injection containing a pharmaceutical composition comprising RNA, where the inner surface of the syringe barrel is free of silicon oil (claims 1 and 3 of Ashmead, and throughout).
Regarding claim 85, Ashmead teaches the use of their syringe for the treatment of ocular disease (e.g., claim 22). A practitioner can therefore immediately envision such a method as injecting a subject with a syringe filled with a pharmaceutical composition of Ashmead, as Ashmead teaches that the syringes can be used for treating diseases (e.g., claim 22).
Regarding claim 87, claim 87 can most broadly be interpreted to simply obtaining a filled syringe such as that recited in claim 1 and storing the syringe for a point in time. Ashmead teaches obtaining pre-filled silicon-free syringes with pharmaceuticals such as RNA (claims 1 and 3). Ashmead therefore anticipates the method of claim 87, as a practitioner can immediately envision filling a syringe to obtain a pre-filled syringe and then keeping the syringe.
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 (i.e., changing from AIA to pre-AIA ) 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 2, 4, 21, 26, and 29-30 are rejected under 35 U.S.C. 103 as being unpatentable over Ashmead (US 2017/0173267 A1, published 6/22/2017) as applied to claims 1, 5-11, 23, 25, 70, 85, and 87 in the 102 rejection, above, in view of Horhota (WO 2020/061457 A1, published 3/26/2020).
The discussion of the teachings of Ashmead with regards to the 102 above are incorporated herein.
Regarding claim 2, Ashmead teaches the syringe of claim 1 (claim 1 of Ashmead). Furthermore, Ashmead teaches that formulations such as RNA can be present in the syringe (e.g., claim 3 of Ashmead).
Ashmead does not specifically teach that the RNA is formulated in a lipid carrier.
Horhota is a patent document which teaches methods of effective administration and preparation of lipid nanoparticles (Title, Abstract, and throughout). Horhota teaches that lipid-based carriers are known to be “effective as transport vehicles into cells and/or intracellular compartments for biologically active substances such as small molecule drugs, proteins, and nucleic acids,” (paragraph 4). Thus, Horhota teaches a motivational to incorporate the use of lipid nanoparticles when delivering a nucleic acid such as RNA, as such carriers are known to improve efficacy of delivering RNA (Background, paragraphs 3-4). Furthermore, Horhota also teaches that such formulations that they teach can be administered using a syringe (e.g., paragraph 186).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the RNA-filled syringes taught by Ashmead to include lipid carriers as taught by Horhota because Horhota teaches that the use of such lipid carriers is known to be beneficial when delivering RNA (above). Furthermore, Horhota teaches that such lipid carriers can be delivered using syringes; thus the combination is not only motivated by the beneficial teachings taught by Horhota but are also predictable because Ashmead also teaches RNA-filled syringes.
Regarding claim 4, per the specification, “long chain” RNA is at least 100 nucleotides in length (e.g., specification at page 12, third paragraph). Horhota teaches that the RNA can be at least 100 nucleotides (e.g., claim 90 of Horhota)
Regarding claim 21, Horhota teaches that doses of RNA can be between 25-100 micrograms, and thus reasonably teaches doses within the recited range in claim 21 (paragraph 606).
Regarding claim 26, Horhota teaches that the nucleic acid can be 1,000 nucleotides in length (paragraph 390).
Regarding claim 29, Horhota teaches that the RNA can comprise pseudouridine (paragraph 402).
Regarding claim 30, Horhota teaches that the RNA can be mRNA (e.g., paragraph 433 and throughout).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DOUGLAS CHARLES RYAN whose telephone number is (571)272-8406. The examiner can normally be reached M-F 8AM - 5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram Shukla can be reached at (571)-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D.C.R./Examiner, Art Unit 1635
/KIMBERLY CHONG/Primary Examiner, Art Unit 1636