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 .
DETAILED ACTION
Status of the Application
Claims 16 and 27-45 are pending. Claims 16 and 27-33 are currently under examination. Claims 51-54 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
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 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.
Claim(s) 1, 2, 8, 9-13, 19-23 and 26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rauch et al. (US 2019/0125857).
Regarding Claim 1, Rauch et al. discloses a composition for inducing an immune response against Norovirus (NoV) in a subject (Para. [0017]). The antigen or immunogen stimulates the body's adaptive immune system to provide an adaptive immune response (Para. [0076]), the composition comprising at least one
mRNA molecule encoding at least one NoV VP2 antigen (Para. [0017]); the artificial nucleic acid molecule according to the invention comprises at least one coding region encoding the Norovirus capsid protein VP2, Para. [0131]).
Regarding Claim 2, Rauch et al. discloses the composition of claim 1, wherein the NoV antigen is selected to be VP2 ([0017]); the artificial nucleic acid molecule according to the invention comprises at least one coding region encoding the Norovirus capsid protein VP2 (Para. [0131]).
Regarding claims 8 and 19, Rauch et al. teach VPI Norvirus having SEQ ID No. 166 identical to instant SEQ ID No. 1 (see alignment below).
Regarding Claim 9, Rauch et al. discloses the composition of claim 1, wherein the composition further comprises an adjuvant (Para. [0053]).
Regarding Claim 10, Rauch et al. discloses the composition of claim 1, wherein the mRNA molecule is encapsulated within a lipid nanoparticle (LNP) (the at least one mRNA of the inventive composition may be complexed with lipids to form one or more. lipid nanoparticles (Para. [0017]); RNA is encapsulated in lipid nanoparticle (LNP) using established protocols known in the art, Para. [0952]).
Regarding Claim 11, Rauch et al. discloses the composition of claim 1, wherein the mRNA molecule is a nucleoside modified mRNA molecule comprising at least one modified nucleoside selected from the group consisting of pseudouridine, 1-methyl pseudouridine, and 5-methyl-uridine (Para. [0293]).
Regarding Claims 12-13, Rauch et al. discloses a method of inducing an immune response against at least one strain of Norovirus (NoV) in a infection with Norovirus, wherein the method comprises administering to a subject in need thereof the artificial nucleic acid according, the inventive composition comprising at least one artificial nucleic acid according to the invention (Para. [0702]) comprising administering to the subject an effective amount of a composition comprising a mRNA molecule encoding at least one VP2 NoV antigen herein (Para. [0647]).
Regarding Claim 20, Rauch et al. discloses the method of claim 12, wherein the composition further comprises an adjuvant (the immunostimulatory composition may comprise an adjuvant, Para. [0053]).
Regarding Claim 21, Rauch et al. discloses the method of claim 12, wherein the mRNA molecule is encapsulated within a lipid nanoparticle (LNP) (the at least one mRNA of the inventive composition may be complexed with lipids to form one or more. lipid nanoparticles (Para. [0017]; RNA is encapsulated in lipid nanoparticle (LNP) using established protocols known in the art, Para. [0952]).
Regarding Claim 22, Rauch et al. discloses the method of claim 22, wherein the mRNA molecule is a nucleoside modified mRNA molecule comprising at least one modified nucleoside selected from the group consisting of pseudouridine, 1-methyl pseudouridine, and 5 -methyl-uridine (Para. [0293]).
Regarding Claim 23, Rauch et al. discloses the method of claim 12, wherein the composition is administered by a delivery route selected from
the group consisting of intradermal, subcutaneous, inhalation, intranasal, and intramuscular (Preferably, jet injection is used for
intradermal, subcutaneous or intramuscular injection of the mRNA sequence according to the invention, Para. [0058]).
Regarding Claim 26, Rauch et al. discloses the method of claim 12, wherein the composition treats or prevents a disease or disorder associated with NoV infection (a method of treating or preventing a disorder, wherein the disorder is preferably an infection with Norovirus or a disorder related to an infection with Norovirus (0702).
Thus the claims are anticipated.
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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 3, 4, 6, 14, 15 and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rauch et al. (US 2019/0125857) and Tan, Ming. ("Norovirus vaccines: current clinical development and challenges." Pathogens 10.12 (2021)) and
Rauch et al. is relied upon as above but does not teach the NOV antigen is one or more of Gi, GII, GIV, GVIII and GIX.
Tan et al. teach Noroviruses are the major viral pathogens causing epidemic and endemic acute gastroenteritis with significant morbidity and mortality and Noroviruses are the major viral pathogens causing epidemic and endemic acute gastroenteritis with significant morbidity and mortality (abstract). Tan et al. teach vaccine candidates in Table 1 and the inclusion of both GI and GII norovirus antigens intends to broaden its potential protective immunity (see page 2.1). Thus it would have been obvious to use mRNA encoding GI alone or in combination for a vaccine in methods to induce an immune response.
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 1, 9-12, 20-23 and 26 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 Norovirus (NoV) antigens, combinations and fragments thereof with the function of inducing any immune response against Norovirus.
When determining whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant case, the specification describes a mRNA encoding GI and GII that induced a strong TH1 response. This example does not encompass the vast number of different NoV antigens such as in claim 2.
It is then determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e. other than nucleotide sequence), specific features and functional attributes that would distinguish different members of the claimed genera. In the instant case, the only other identifying characteristics are the specification describes a mRNA encoding GI and GII that induced a strong TH1 response. 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 a vast number of sequences of promoters and functional fragments of a Connexin 26 protein with the function of expression in any type of inner ear support cell, 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 mRNA expressing any NoV antigen capable of induced any type of immune response. 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.
Enablement
Claims 12-15, 17, 19-23 and 26 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claims 12-15, 17, 19-23 and 26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods of induced a Th1 response using a mRNA encoding GI and GII, does not reasonably provide enablement for using any NoV antigen or fragment thereof to induce any immune response. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The following factors have been considered in the analysis of enablement: (1) the breadth of the claims, (2) the nature of the invention, (3) the state of the prior art, (4) the level of one of ordinary skill, (5) the level of predictability in the art, (6) the amount of direction provided by the inventor, (7) the existence of working examples, (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims the nature of the invention:
The broadest reasonable interpretation is using a mRNA encoding any NoV antigen or fragment thereof or combination of the claimed antigens to induce any immune response in a subject.
Whether the specification would have been enabling as of the filing date involves consideration of the nature of the invention, the state of the prior art, and the level of skill in the art. The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed. See MPEP § 2164.05(b). The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification.
The state of the prior art:
The prior art teach the human noroviruses are genetically and antigenically diverse, consisting of five genogroups (GI, GII, GIV, GVIII, and GIX) which comprise 35 genotypes. Multiple variants of various genotypes are often detected simultaneously (see page 1-2 Tan et al cited above). Tan et al. teach there are four norovirus vaccine under clinical evaluations comprising GI and GII variants (Table 1). The prior art does not describe using the vast number of antigens and fragments thereof.
The level of one of ordinary skill:
While the level of one of ordinary skill practicing said invention would be high, the level of predictability is considered variable as evident in the prior art discussed above and is not considered to provide sufficient enablement to practice the claimed invention.
Because the state of the prior art does not provide evidence of the degree of predictability that methods for inducing any immune response can occur using a mRNA encoded by any NoV antigen, combinations or fragments thereof, one of ordinary skill in the art would look for guidance or direction in the instant specification.
The level of predictability in the art:
“The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability.” (MPEP 2164.03).
The amount of direction provided by the inventor:
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. >See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004).
The existence of working examples:
The working embodiment in the instant application describes inducing a Th1 immune response using mRNA encoded with NoV antigens GI and GII. The working embodiments do not describe using any mRNA encoding any NoV antigen, combinations and fragments thereof to induce any immune response.
The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004).
While the MPEP 2164.02 states the specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970), the lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
Without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention.
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Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly Chong at (571)272-3111. The examiner can normally be reached Monday thru Friday between M-F 8:00am-4:30pm.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636
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