Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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.
DETAILED ACTION
Claim status
Claims 1-20 are pending
Claims 3-13 are withdrawn
Claims 1-2, 14-20 are under examination
Species Election
Applicant’s election of the following species in the reply filed on 5/21/2026 is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-2, and 14-20, drawn to a PLGA microsphere.
Claims 3-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic claim.
Priority
The instant application was 3/02/2023 and This application is a CON of 16/525,145 filed 07/29/2019, which is a CON of 15/621,693 filed 06/13/2017, which is a CON of 15/077,705 filed 03/22/2016, which is a DIV of 13/714,458 filed 12/14/2012, which claims priority to PRO 61/712,490 filed 10/11/2012, PRO 61/709,303 filed 10/03/2012, PRO 61/696,381 filed 09/04/2012, PRO 61/681,712 filed 08/10/2012, PRO 61/648,244 filed 05/17/2012, PRO 61/618,957 filed 04/02/2012, and PRO 61/576,705 filed 12/16/2011.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 61/648,244 filed 05/17/2012, PRO 61/618,957 filed 04/02/2012, and PRO 61/576,705 filed 12/16/2011, fail to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. Review of these applications did not reveal support for a method of comprising a PLGA microsphere with a diameter between 4-20 microns as per claim 16. Thus the instant claim 16 is being given the filing date of 8/10/2012.
Information Disclosure Statement
No information disclosure statement (IDS) has been submitted.
Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112(a)
NEW MATTER
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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.
Claims 17-19 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 new limitations of “modified mRNA release less than 50% of the modified mRNA in a 48 hour time-period” as per claim 17, the “modified mRNA is stable in serum” as per claim 18, and the “stability is determined relative to unformulated modified mRNA in 90% serum” as per claim 19 appear to represent new matter. MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112(a), pre-AIA first paragraph - written description requirement. In re Rasmussen , 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” Although the basis for this limitation was identified in Applicant’s remarks filed 10/16/2023 paper as not adding new matter, a review of the specification by the Examiner did NOT find any specific basis for the recited limitations directed to release rate nor serum stability. As noted by the MPEP, new matter includes not only the addition of wholly unsupported subject matter, but may also include the introduction of claim changes which involve narrowing the claims by introducing elements or limitations which are not supported by the as-filed disclosure is a violation of the written description requirement of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph. See, e.g., Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996). In Ex parte Ohshiro, 14 USPQ2d 1750 (Bd. Pat. App. & Inter. 1989), the Board affirmed the rejection under 35 U.S.C. 112, first paragraph, of claims to an internal combustion engine which recited "at least one of said piston and said cylinder (head) having a recessed channel." The Board held that the application which disclosed a cylinder head with a recessed channel and a piston without a recessed channel did not specifically disclose the "species" of a channeled piston (see MPEP 2163.05 (II) Narrowing or Subgeneric Claim).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived 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(a) 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 1-2, 15, and 18 are rejected under 35 U.S.C. 103(a) as being unpatentable over Hoerr et al. (US2008/0171711, filed 7/20/2005, published 7/17/2008), in view of Hoerr et al. (US2006/0188490, filed 1/30/2006, published 8/24/2006)
Hoerr (2008) teaches method of producing a polypeptide of interest (i.e., vaccine) in a mammalian cell or tissue by contact with a modified mRNA (Abstract, [0018-0019, 0078-0080,m 0135-0136].
Furthermore, although Hoerr (2008) teaches the modified mRNA is formulated with lactide-glycolide copolymer [0134], Hoerr (2008) is silent to formulating the mRNA into a PLGA microsphere.
Nevertheless, formulation of nucleic acids in PLGA microspheres was well known in the prior art, and in her prior patent application Hoerr (2006) explicitly teaches formulating the modified mRNA into a PLGA microparticle [0037].
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to practice a method of producing a polypeptide of interest by contacting the cell or tissue with a modified mRNA as taught by Hoerr (2008), and choose the formulation of the mRNA into a PLGA microparticle as taught by Hoerr (2006) with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Hoerr (2006) because PLGA microspheres allow for efficient transfer of the mRNA into cells [0037]. Furthermore, it would have been obvious to one of ordinary skill to have turned to related disclosures from the same inventor to seek out modification/improvements on a method.
In regard to claim 2, Hoerr (2008) teaches the mRNA comprises a purified in vitro translated transcript [0064, 0138-0142].
In regard to claim 15, as stated supra, Hoerr (2006) makes obvious a PLGA microsphere.
In regard to claim 18, Hoerr (2008) teaches the modified mRNA is more resistant to degradation by RNAases [0005, 0009, 0068, 0124], and therefore would have been stable in serum. Furthermore, the functional language of “serum stable” does not change the structure of the modified mRNA nor does it make a manipulated difference in the taught method.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 14 is rejected under 35 U.S.C. 103(a) as being unpatentable over Hoer et al. (US2008/0171711), in view of Hoerr et al. (US2006/0188490, filed 1/30/2006, published 8/24/2006), as applied to claim 1, in further view of Yurek et al. (Mol Imag, 2011, 10(5):327-339).
As stated above, Hoerr (2008) in view of Hoerr (2006) suggest a method of producing a polypeptide of interest in a mammalian cell or tissue comprising administering a composition comprising a modified mRNA formulated with PLGA microspheres.
In regard to claim 14, although Hoerr (2008) teaches the method is to treat brain tumors such as glioma [0072, 0146-147], and the contacting step for the modified mRNA is by injection into the tumor tissue [0019-0020], they are silent with respect to using a syringe pump.
In regard to claim 14, Yurek teaches method of producing a polypeptide of interest in a mammalian tissue comprising administering a composition comprising a nucleic acid particle to brain tissue comprising a pump-driven Hamilton microsyringe (p. 3, Materials and Methods, 4th para.).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to practice a method of producing a polypeptide of interest in the brain tumor tissue as suggested by Hoerr et al., and choose a pump-driven syringe as taught by Yurek with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Yurek because this means of delivery allows small volumes to be precisely delivered to tissue (p. 3, 4th para., p. 7, last para.).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 16-17 and 19-20 are rejected under 35 U.S.C. 103(a) as being unpatentable over Hoerr et al. (US2008/0171711, filed 7/20/2005, published 7/17/2008), in view of Hoerr et al. (US2006/0188490, filed 1/30/2006, published 8/24/2006), as applied to claims 1, 15 and 18, in further view of Hedley et al., (WO1998/31398, filed 1/22/1998, published 7/23/1998).
As stated above, Hoerr (2008) in view of Hoerr (2006) suggest a method of producing a polypeptide of interest in a mammalian cell or tissue comprising contacting a composition comprising a modified mRNA formulated with PLGA microspheres.
However, Hoerr et al. do not describe the properties of an mRNA formulated with a PLGA microsphere with respect to diameter, release kinetics, measured stability, or % weight loading.
Nevertheless, Hedley teaches nucleic acids formulated with PLGA microspheres, and specifically teaches PLGA is an effective copolymer for introducing nucleic acids into host cells, as it is a biodegradable copolymer known to be cleared from host cells by normal metabolic pathways (p. 3, 2nd para., p. 15, 3rd para.). Furthermore, Hedley teaches methods for formulating a nucleic acid with PLGA by double-emulsion techniques (p. 6, last para. to p. 12, p. 21, last para. to p. 22).
In regard to claim 16, Hedley teaches the PLGA microspheres are less than about 20 microns in diameter, more preferably less than about 11 microns in diameter, and provides a preferred embodiment where the peak diameter of microspheres is about 6 microns (p. 2, 2nd & last para., p. 4, 2nd para., p. 6, 2nd para., p. 15, 3rd para., p. 31, 3rd para., see Fig. 2).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to practice a method of comprising a modified mRNA formulated in PLGA microsphere as suggested by Hoerr et al., and choose a formulation with microspheres of about 6 microns in diameter as taught by Hedley with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Hedley because PLGA microparticles in this size range (i.e., under 11 microns) are an effective means for introducing nucleic acids into macrophages, dendritic cells, and other APCs (P. 15, 3rd para.), which would have been ideal for the mRNA based vaccination methods of Hoerr (2008). Furthermore, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. See M.P.E.P. §2144.05.
In regard to claim 17, Hedley teaches that PLGA allows controlled release of the encapsulated nucleic acids as the polymer biodegrades (p. 3, 2nd para., p. 21, last two para.). In regard to the rate of release, Hedley teaches the polylactic acid component takes a year to degrade in vivo, thus it would have been expected that less than 50% of the nucleic acid would be released in the serum in vivo. Furthermore, the functional language directed to release rate does not change the structure of the modified mRNA nor does it make a manipulated difference in the taught method.
In regard to claim 19, Hoerr (2008) teaches the modified RNA is administered to the blood stream of the mammal, and the unmodified mRNA has a short half-life in the bloodstream [0005, 0009, 0068]. In regard to testing the PLGA formulation’s stability against RNAases in the bloodstream, although Hedley teaches testing for degradation by HPLC or gel electrophoresis (p. 26, 1st para.), the use of serum would have been obvious to more accurately reflect conditions in vivo. As far as the percent of serum used, it has been discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233.
In regard to claim 20, Hedley teaches that nucleic acids can be encapsulated with percentages of incorporation ranging from 11% to 82% depending on the conditions (pgs. 35-41, see Tables). Again, it would have been obvious to optimize the percent incorporation of the mRNA into the PLGA microspheres because discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-2, 15, 17-20 are rejected on the grounds of nonstatutory double patenting over claims 1-9 of U.S. Patent No. 9,295,689 (de Fougerolles et al., Patented 3/29/2016).
The subject matter claimed in the instant application is fully disclosed in the referenced patent as follows: the method for producing a protein a protein of interest in a cell comprising contacting the cells with a modified mRNA formulated in a PLGA microsphere of cited patent anticipates the method of instant application. It is clear that all the elements of the cited patent claims are to be found in instant claims. The difference between the cited patent claims and the instant claims lies in the fact that the cited patent claims are much more specific with respect to the modifications, % wt, and size. Note that in vitro translation is an implicit limitation of this type of modified mRNA. Thus the invention of said claims of the cited patent are in effect “species” of the “generic” invention of the instant claim. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Since the instant application claims are anticipated by and/or obvious over cited patent claims, said claims are not patentably distinct.
Claim 14 is rejected on the grounds of nonstatutory double patenting over claims 1-9 of U.S. Patent No. 9,295,689 (de Fougerolles et al., Patented 3/29/2016), in view of Yurek et al. (Mol Imag, 2011, 10(5):327-339).
The subject matter claimed in the instant application is fully disclosed in the referenced patent as follows: the method for producing a protein a protein of interest in a cell comprising contacting the cells with a modified mRNA formulated in a PLGA microsphere of cited patent by intrathecal makes obvious the method of instant application. It is clear that all the elements of the cited patent claims are to be found in instant claims. The difference between the cited patent claims and the instant claims lies in the fact that the instant claim uses a syringe pump.
In regard to claim 14, Yurek teaches method of producing a polypeptide of interest in a mammalian tissue comprising administering a composition comprising a nucleic acid particle to the brain comprising a pump-driven Hamilton microsyringe (p. 3, Materials and Methods, 4th para.).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to practice a method of producing a polypeptide of interest by intrathecal delivery as claimed by cited patent, and choose a pump-driven syringe as taught by Yurek with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Yurek because this means of delivery allows small volumes to be precisely delivered to the brain (p. 3, 4th para., p. 7, last para.).
Since the instant application claims are obvious over cited patent claims in view of Yurek, said claims are not patentably distinct.
Claims 1-2, 15, 17-20 are rejected on the grounds of nonstatutory double patenting over claims 1-9 of U.S. Patent No. 9,271,996 (de Fougerolles et al., Patented 3/01/2016).
The subject matter claimed in the instant application is fully disclosed in the referenced patent as follows: the method for producing a protein a protein of interest in a cell comprising contacting the cells with a modified mRNA formulated in a PLGA microsphere of cited patent anticipates the method of instant application. It is clear that all the elements of the cited patent claims are to be found in instant claims. The difference between the cited patent claims and the instant claims lies in the fact that the cited patent claims are much more specific with respect to the modifications, % wt, and size. Note that in vitro translation is an implicit limitation of this type of modified mRNA. Thus the invention of said claims of the cited patent are in effect “species” of the “generic” invention of the instant claim. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Since the instant application claims are anticipated by and/or obvious over cited patent claims, said claims are not patentably distinct.
Claim 14 is rejected on the grounds of nonstatutory double patenting over claims 1-9 of U.S. Patent No. 9,271,996 (de Fougerolles et al., Patented 3/01/2016), in view of Yurek et al. (Mol Imag, 2011, 10(5):327-339).
The subject matter claimed in the instant application is fully disclosed in the referenced patent as follows: the method for producing a protein a protein of interest in a cell comprising contacting the cells with a modified mRNA formulated in a PLGA microsphere of cited patent by intrathecal makes obvious the method of instant application. It is clear that all the elements of the cited patent claims are to be found in instant claims. The difference between the cited patent claims and the instant claims lies in the fact that the instant claim uses a syringe pump.
In regard to claim 14, Yurek teaches method of producing a polypeptide of interest in a mammalian tissue comprising administering a composition comprising a nucleic acid particle to the brain comprising a pump-driven Hamilton microsyringe (p. 3, Materials and Methods, 4th para.).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to practice a method of producing a polypeptide of interest by intrathecal delivery as claimed by cited patant, and choose a pump-driven syringe as taught by Yurek with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Yurek because this means of delivery allows small volumes to be precisely delivered to the brain (p. 3, 4th para., p. 7, last para.).
Since the instant application claims are obvious over cited patent claims in view of Yurek, said claims are not patentably distinct.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
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