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 .
Response to Applicants Arguments/Amendments
Claim 30 has been canceled, therefore, the duplication of claims warning present in the former office action dated April 3, 2026 has been withdrawn. The former 112(b) rejection has also been removed since claim 31 has been canceled. The response to each set of arguments for each art rejection will be addressed directly below the appropriate art rejection. The examiner decided to make the Garver rejection a 103 rejection instead of a 102 rejection. Therefore, this action is a non-final.
Election/Restrictions
Newly submitted claims 32-34 are directed to inventions that are independent or distinct from the invention originally claimed for the following reasons: In the restriction dated January 1, 2026, methods for storage (Group IV), transportation (Group III), and fulfilling an order (Group V) were not elected by applicant. Applicant chose Group II (method of preparation) which is currently the elected set of claims. Newly elected claims 32-34 recite storage, transportation, and fulfillment methods. Since applicant has received an action on the merits for the originally presented invention (Group II), these inventions have been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 32-34 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claim Rejections - 35 USC § 102
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 12-14,24,26, and 35-37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chetverin (5,616,478)
Chetverin discloses a method of preparing a sample comprising extracellular RNA for storage, the method comprising the steps of: i) contacting the sample with a hydrogel-forming polymer; and ii) polymerizing the polymer to form a reversibly cross-linked RNA-containing hydrogel (Columns 7,9-10, Figure 2 and its brief description). The structure of Chetverin’s hydrogel would inherently allow for storage/transporting for at least 24 hours, storage/transporting at a temperature of 0 to 32°C, and storage/transporting for at least one mile as in instant Claims 12,35-37. Chetverin discloses mixing the extracellular RNA with an aqueous buffer prior to step (i) (Column 1, line 23-25 of Chetverin) as in instant Claim 13. Chetverin discloses sealing the RNA-containing hydrogel into a receptable for storage (Column 8, ln 35-50 of Chetverin) as in instant Claim 14. Chetverin discloses an aqueous buffer (Column 1, line 20-30) as in instant Claim 24. Chetverin discloses wherein the hydrogel comprises cross-linked calcium alginate (Column 9, last paragraph of Chetverin) as in instant Claims 26.
The references anticipates the claim limitations.
Response to Applicants Arguments
The examiner agrees with applicant that Example 1 does not teach the claimed invention of a hydrogel polymer that holds RNA in a manner that can be used for a storage capacity. The examiner will redact Example 1 as a teaching in the 102 rejection. However, the 102 rejection still stands because columns 9 and 10 still teach the claimed invention.
Applicants further argue 9 and 10 state, “these passages relate to nucleic acid/template broadly, not RNA. There is nothing in Chetverin that suggests the resulting sandwich medium is suitable for storage and/or transport of RNA. In fact, the purpose of the sandwich medium is to spatially confine amplification products and enable the detection of amplified nucleic acid colonies.”
Columns 9, line 20 to Column 10, line 42 describe how the nucleic acid can be encapsulated in a granule. This granule is subsequently coated with alginate that is then calcium crosslinked (Part (b) column 9 spanning column 10). Column 10, part b further details that the contents encapsulated within the alginate can be released by simply chelating calcium. The system envisioned in columns 9 and 10 encompasses both RNA and DNA (nucleic acid). The brief drawing descriptions further expressly state that Chetverin’s invention applies to RNA. Columns 9 and 10 of Chetverin are concerned with amplification and expression of nucleic acids. However, while these activities are occurring, the alginate outer shell material can still be considered appropriate for storage because it is holding/maintaining the nucleic acids. The claims do not add further structure and/or function to the hydrogel to distinguish it from the teachings of Chetverin.
Claim Rejections - 35 USC § 103
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 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.
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 12,21-22,26,30, and 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over Garver (US 6,916,490).
Garver discloses a method of preparing a sample comprising extracellular RNA for storage, the method comprising the step of: contacting the sample with a hydrogel-forming polymer; and polymerizing the polymer to form a reversibly cross-linked RNA containing hydrogel. The example with cross linking is for DNA; Garver teaches that RNA and DNA can be successfully placed in protective hydrogels. It would have been obvious to have placed RNA in a crosslinked hydrogel, allowing the RNA to be released at a specific target since DNA can be successfully released in that manner (Abstract; Column 2, ln 55-67;Column 3, ln 15-20; Column 7, ln 15-20; Column 8, ln 10-20 ;Column 14, ln 1-28; Column 21, ln 58-65 of Garver) The structure of Garver’s hydrogel would allow for storage transporting for at least 24 hours, storage/transporting for at least 24 hours, and or storage/transporting for at least one mile as in instant Claims 12,35-37. Garver discloses wherein the extracellular RNA is within a lipid capsule (Column 4, ln 2 of Garver) as in instant Claim 21. Garver discloses wherein the extracellular RNA is a viral vector or a viral particle (Column 15, ln 1-5; Column 19 of Garver) as in instant Claim 22. Garver discloses wherein the hydrogel comprises cross-linked calcium alginate (Column 14, ln 1-28; Claim 29, Clam 31 of Garver) as in instant Claim 26 and 30.
Garver teaches a hydrogel containing RNA; Garver further teaches that cross linked alginate can be used to target deliver nucleic acid. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicants’ invention, it must be considered absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combinations would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, and engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have practical knowledge in nucleic acid delivery systems. Therefore, the level of ordinary skill in the art is high.
Claims 12-14, 24,26-27 and 30-31, 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over Chetverin (5,616,478) in view of C.l Bucke “Cell Immobilization in Calcium Alginate” Methods in Enzymology, Volume 135, 1987, Pages 175-189.
Chetverin applies as above to teach claims 12-14, 24,26, 30, 35-37. Chetverin does not specifically teach the amount of calcium-alginate. However, the Chetverin reference does refer to the reference, Bucke “Cell Immobilization in Calcium Alginate” Methods, Enzymol. 135, 175-189 when discussing calcium-alginate. Bucke teaches that the amount of calcium alginate in such a composition can be about 2.4% (Page 188, 4th paragraph). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have used the amount of calcium-alginate taught by Bucke. An artisan would have been motivated to have used Bucke’s amount of calcium alginate since it allows for the successful encapsulation of a biological specimen and preserves the activity of that biological specimen (Page 188, 4th paragraph of Bucke). Because that concentration of calcium alginate allows for the successful encapsulation of a biological specimen, there would have been a high expectation for success (Page 188, 4th paragraph of Bucke) as in instant Claims and 27 and 31.
Chetverin teaches a hydrogel that comprises a cross-linked calcium alginate but does not teach the precise amount of calcium alginate. An artisan would have been motivated to have used the amount of calcium alginate taught by Bucke (2.4%) since it successfully preserves the activity of the encapsulated biological specimen. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicants’ invention, it must be considered absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combinations would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007)). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, and engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have practical knowledge in nucleic acid delivery systems. Therefore, the level of ordinary skill in the art is high.
Response to Applicants Arguments
Applicants argue that Bucke fails to cure the deficiencies of Chetverin. Because Chetverin is not deficient as argued above, Bucke is not defective. Applicants further argue that, one would not have applied the Bucke reference since it does not directly deal with stabilizing and preserving extracellular RNA for long term storage and transport. Bucke is not relied upon for a method of preparing a structure that can be used for storage; Chetverin is relied upon for this specific teaching. Bucke teaches that encapsulating a biological specimen with an amount of calcium alginate of 2.4% allows for successfully encapsulation of a biological specimen while preserving the activity of a biological specimen. It would have been obvious to have used this precise amount in Chetverin since it does not impair biological specimens.
Claims 12,21-22,26-27, and 30-31,35-37 are rejected under 35 U.S.C. 103 as being unpatentable over Garver (US 6,916,490) in view of C.l Bucke “Cell Immobilization in Calcium Alginate” Methods in Enzymology, Volume 135, 1987, Pages 175-189.
Garver applies as above to teach claims 12,21-22, 26, 30, 35-37 . Garver does not teach the amount of calcium-alginate. Bucke teaches that the amount of calcium alginate in such a composition can be about 2.4% (Page 188, 4th paragraph of Bucke). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have used the amount of calcium-alginate taught by Bucke. An artisan would have been motivated to have used Bucke’s amount of calcium alginate solution since it allows for the successful encapsulation of a biological specimen and preserves the activity of the biological specimen (Page 188, 4th paragraph of Bucke). Because that concentration of calcium alginate allows for the encapsulation of a biological specimen and preserves its activity, there would have been a high expectation for success (Page 188, 4th paragraph of Bucke) as in instant Claims and 27 and 31.
Garver teaches a hydrogel containing RNA; Garver further teaches that cross linked alginate can be used to target deliver nucleic acid. Garver does not teach the precise amount of calcium alginate. An artisan would have been motivated to have used the amount of calcium alginate taught by Bucke (2.4%) since it successfully preserves the activity of the encapsulated biological specimen. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicants’ invention, it must be considered absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combinations would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, and engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have practical knowledge in nucleic acid delivery systems. Therefore, the level of ordinary skill in the art is high.
Response to Applicants Arguments
Garver is now a 103 rejection instead of a 102 rejection. Applicants further argue that, one would not have applied the Bucke reference since it does not directly deal with stabilizing and preserving extracellular RNA for long term storage and transport. Bucke is not relied upon for teaching a method of preparing a hydrogel that is capable of being used for storage; Garver is relied upon for this specific teaching. Bucke teaches that encapsulating a biological specimen with an amount of calcium alginate of 2.4% allows for successfully encapsulation of a biological specimen while preserving the activity of a biological specimen. It would have been obvious to have used this precise amount in Garver since it does not impair biological specimens.
Unexpected results argument
Applicants further argue the following:
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The instant claims recite a method of preparing an RNA encapsulated in a hydrogel and do not provide additional features/structure/function that distinguish the hydrogel from the hydrogels present in the primary prior art references. The claims do not address how well the RNA/RNA virus is preserved. If there are improvements based on specific hydrogel structures, then those structures need to be introduced into the instant claims.
Conclusion
All claims stand rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
