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 Application/Amendment/Claims
Applicant's response filed 05/26/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 01/27/2026 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
With entry of the amendment filed on 05/26/2026, claims 48-50 and 53-71 are pending in the application.
SEQ ID Nos. 92-94, 15-17 and 217-221 have been rejoined and examined.
Claims 48-50, 53, 70 and 71 are free of the prior art and allowable.
Claims 54-69, previously withdrawn a being drawn to a non-elected invention are rejoined and examined.
New Claim Rejections necessitated by claim amendments
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 60-64 and 66 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 pre-AIA the applicant regards as the invention.
Claim 60 recites “c) introducing into the cell a heterologous polynucleotide encoding the secreted protein, wherein the secreted protein is not naturally produced by the cell”. This claim depends from claim 54 which recites “the mammalian cell produces a secreted protein” and it is unclear how the secreted protein can be produced by the cell and also introduced into the cell by a heterologous polynucleotide. Claims 61-64 are rejected as they depend from claim 60 and have the same indefiniteness.
Claim 66 recites “identifying the cell with the polynucleotide integrated into the genome” and is indefinite because if the polynucleotide of claim 49 is introduced into the mammalian cell, wouldn’t the cell type be known? It is unclear how the cell is identified when this method can be performed in vitro with a known cell line and also performed in vivo.
Claim Rejections - 35 USC § 112
Enablement
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.
Claims 54-69 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 generating an inhibitory polynucleotide comprising or encoding multi-amiRNA hairpins with guides complementary to each of Neu2 and Neu3 mRNAs comprising (i) a first guide strand sequence comprising a contiguous 19 or 20 or 21 or 22 nucleotide sequence that is perfectly complementary to a natural mammalian cellular mRNA encoding a Neu2 sialidase and (ii) a first passenger strand sequence comprising a contiguous 19 or 20 or 21 or 22 nucleotide sequence that is at least 78% complementary to the first guide strand sequence, wherein the first guide strand and first passenger strand sequence are separated by between 5 and 35 nucleotides and (iii) a second guide strand sequence comprising a contiguous 19 or 20 or 21 or 22 nucleotide sequence that is perfectly complementary to the same natural mammalian cellular mRNA encoding a Neu2 sialidase as the first guide strand sequence,
does not reasonably provide enablement for increasing the sialic acid content of proteins produced by any cell type using a polynucleotide that comprises or encodes the claimed multi-hairpin amiRNA sequences flanked by any transposon ends and a corresponding transposase whereby the cell produces any secreted protein with an increase level of sialylation compared to a control.
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 and the nature of the invention:
The broadest reasonable interpretation of the claims is a method of increasing sialylation in a mammalian cell by introducing a polynucleotide comprising a multi-amiRNA flanked by any transposon ends and a corresponding transposase whereby the cell produces a secreted protein with an increase level of sialylation compared to a control.
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:
Ngantung et. al. (2006. Biotechnol. Bioeng. 95, 106-119. “RNA interference of sialidase improves glycoprotein sialic acid content consistency) demonstrates increasing sialylation in Cho cells by using RNAi to knockdown the activity of sialidase which is responsible for cleaving sialic acid (see page 107 3rd para). A review of the prior art does not teach using a composition comprising a polynucleotide and a multi-amiRNA polynucleotide sequence flanked by any transposon and any corresponding transposase that is capable of producing any secreted protein with an increased level of sialylation.
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 increasing sialylation can occur using the claimed multi-amiRNA polynucleotide sequence flanked by any transposon and any corresponding transposase that is capable of producing any secreted protein, 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 generating an inhibitory polynucleotide comprising or encoding multi-amiRNA hairpins with guides complementary to each of Neu2 and Neu3 mRNAs comprising (i) a first guide strand sequence comprising a contiguous 19 or 20 or 21 or 22 nucleotide sequence that is perfectly complementary to a natural mammalian cellular mRNA encoding a Neu2 sialidase and (ii) a first passenger strand sequence comprising a contiguous 19 or 20 or 21 or 22 nucleotide sequence that is at least 78% complementary to the first guide strand sequence, wherein the first guide strand and first passenger strand sequence are separated by between 5 and 35 nucleotides and (iii) a second guide strand sequence comprising a contiguous 19 or 20 or 21 or 22 nucleotide sequence that is perfectly complementary to the same natural mammalian cellular mRNA encoding a Neu2 sialidase as the first guide strand sequence. The working embodiments do not describe methods for increasing sialylation in any mammalian cell using the claimed polynucleotide.
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:
The prior art is undeveloped for using multi-amiRNA polynucleotides, as claimed, comprising transposons and corresponding transposase targeted to any gene and administered to any mammalian cell type to allow the cell to a secrete protein with increased levels of sialylation. The specification does not provide sufficient guidance and for an enabling disclosure, one of skill in the art must be able to make and use the invention with a reasonable expectation of success and not to make and test if the invention actually works. 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).
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.
Written Description
Claims 54-69 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 compositions comprising a multi-hairpin amiRNA having any two of SEQ ID Nos. 91-94 flanked by any transposon ends and corresponding transposase with the function of increasing the level of sialylation in any secreted protein from any mammalian cell.
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 multi-hairpin amiRNA having various nucleotide sequences cloned into Bombyx transposon vectors and used to suppress FUT8 expression in a single CHO cell type (0222-0226). This example does not encompass the vast number of different comprising a multi-hairpin amiRNA having any two of SEQ ID Nos. 91-94 flanked by any transposon ends and corresponding transposase. The Specification further describes one multi-hairpin amiRNA that is used to inhibit sialidases in [00274] wherein the mRNA encodes Neu2
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 multi-hairpin amiRNA having various nucleotide sequences cloned into Bombyx transposon vectors and used to suppress FUT8 expression in a single CHO cell type. The disclosure has not described this composition or any of the claimed compositions with the broad function of increasing the level of sialylation in any secreted protein from any mammalian cell.
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, 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 variation of the claimed composition with the claimed function. 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.
Closest prior art
Claims 48-50, 53 and 70-71 are free of the prior art. The prior art of Zhang et al. ("Enhancing glycoprotein sialylation by targeted gene silencing in mammalian cells." Biotechnology and bioengineering 105.6 (2010): 1094-1105 of record 892 01/27/2026) teach siRNA sequences designed to target CHO sialidase genes as shown in Table II. Zhang et al. does not teach the claimed SEQ ID Nos. 92-94, 15-17 and 217-221.
The prior art of Watts et al. ("Silencing disease genes in the laboratory and the clinic." The Journal of pathology 226.2 (2012): 365-379 of record 892 01/27/2026) designing inhibitory oligonucleotides can be challenging using different programs wherein each program results in different siRNAs that have to be further tested to determine if they can reduce the target sequence in a cell. Thus nothing in Watts et al. would lead one of skill in the art to a predictable computational tool to design siRNA sequences targeted sialidase genes. There is no motivation for one of skill in the art to identify any specific region of a sialidase gene to target, then choose any of the computational tools to design the claimed sequence to arrive at the claimed amiRNA having SEQ ID Nos. 90 and 91 or the polynucleotide of SEQ ID No. 568. Lastly there is not a finite number of identified and predictable solutions to make it obvious to try because the prior art does not teach a target region that would predictable yield oligonucleotides having SEQ ID No. 90-94, 15-17, 217-221, 570 and 568. (MPEP 2143 KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007)).
Further, it would not have been obvious to try making the claimed composition comprising multi-hairpin amiRNA, transposons and transposase to increase sialic aid in cells given Ngantung et. al. (cited above) teach methods of enhancing sialylation using RNAi targeted to Neu2 in CHO cells. One of skill in the art would not have had a reason to using multi-hairpin amiRNA targeted to this known gene given it was shown to efficiently be inhibited by a siRNA which efficiently enhanced sialylation of CHO cells.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a).
706.07(a) Final Rejection, When Proper on Second Action [R-07.2015]
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Second or any subsequent actions on the merits shall be final, except where the examiner introduces a new ground of rejection that is neither necessitated by applicant’s amendment of the claims, nor based on information submitted in an information disclosure statement filed during the period set forth in 37 CFR 1.97(c) with the fee set forth in 37 CFR 1.17(p). Where information is submitted in an information disclosure statement during the period set forth in 37 CFR 1.97(c) with a fee, the examiner may use the information submitted, e.g., a printed publication or evidence of public use, and make the next Office action final whether or not the claims have been amended, provided that no other new ground of rejection which was not necessitated by amendment to the claims is introduced by the examiner. See MPEP § 609.04(b).
Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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 9-5 pm.
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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