DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claims
The preliminary amendments received on Sept. 5, 2023, has been entered. Claims 14-21 have been canceled. Claims 1-13 are pending and are examined in this Office Action.
Specification
The use of the term BLAST, which is a trade name or a mark used in commerce, has been noted in this application on pages 8 and 101. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112
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.
Lack of Scope of Enablement
Claims 1-13 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 a DNA molecule comprising a sequence with at least 99% identity to SEQ ID NO: 233 and having intron-mediated enhancer activity, does not reasonably provide enablement for a DNA molecule with at least 85% identity to SEQ ID NO: 233, or a fragment with gene-regulatory activity other than enhancer activity. 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. All dependent claims are included in this rejection unless they include a limitation that overcomes the deficiencies of the parent claim.
The claimed invention is not supported by an enabling disclosure taking into account the Wands factors. In re Wands, 858/F.2d 731, 8 USPQ2d 1400 (Fed. Cir. 1988). In re Wands lists a number of factors for determining whether or not undue experimentation would be required by one skilled in the art to make and/or use the invention. These factors are: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples of the invention, the nature of the invention, the state of the prior art, the relative skill of those in the art, the predictability or unpredictability of the art, and the breadth of the claim.
Claim 1 is broadly drawn to a DNA molecule comprising a sequence with at least 85% identity to SEQ ID NO: 233 wherein the sequence is operably linked to a heterologous transcribable polynucleotide molecule.
Claim 4 depends from claim 1 an requires that “the DNA sequence comprises a regulatory element”, and this necessarily means that the genus of sequences encompassed by claim 1 includes sequences that both comprise a regulatory element and do NOT comprise a regulatory element. The Applicant defines a regulatory element as “a DNA molecule having gene regulatory activity” and defines “gene regulatory activity” as “the ability to affect the expression pattern of an operably linked transcribable polynucleotide molecule by affecting the transcription and/or translation of that operably linked transcribable polynucleotide molecule” (Spec 6). Therefore, claim 1 encompasses sequences that do not comprise the ability to affect the expression pattern of an operably linked transcribable polynucleotide molecule.
The Applicant teaches analysis of genomic sequences from different plants, including Setaria italica, and identification of putative promoters, leaders, introns, and transit sequences (Id. 26) and putative introns (Id. 136-137). Applicant teaches multiple sequences that are putative introns, including the claimed sequence of SEQ ID NO: 233 (Id. 137-139). Applicant teaches the relative expression level of the reporter protein, b-glucuronidase (GUS), in transient protoplast assays (Id. 137-139). The expression level is in comparison to a control intron. Table 22 (Spec 137-139) shows intron-mediated enhancement of GUS expression relative to I-Zm.DnaK-1:1:1 (Sequence ID NO: 1102). The expression level for the claimed intron (SEQ ID NO: 233) was a mean of 1.53 with standard deviation of 0.52 compared to the control that was designated as 1.0. It appears that all constructs utilized a CaMV 35S promoter with the different introns operably linked followed by the GUS coding sequence (Spec 136 and Fig. 15).
Applicant does not teach any sequences that are asserted to have no regulatory activity. Applicant does not teach any sequences with at least 85% identity to SEQ ID NO: 233 or sequences that are fragments of SEQ ID NO: 233 that are purported to have any regulatory activity other than the enhancer activity associated with an intron.
See, for example, Rose, A. B. (RNA (2002) Vol. 8; pp. 1444-1453) who teaches that deletions and mutations of nucleotides in an intron lost the ability to regulate the expression of a transgene (Rose 1444-1448). Rose teaches that none of the structural characteristics that are shared between the PAT1 intron and other dicot introns are essential for intron-mediated enhancer activity (Id. 1448). This shows that there is a high degree of unpredictability regarding which nucleotides within an intron are necessary for enhancer activity.
Part (c) of claim 1 does not include any minimum size for the claimed fragments, and part (a) allows for 15% of the nucleotides to be altered. SEQ ID NO: 233 is 1014 nucleotides in length, therefore the genus of molecules encompassed by claim 1 is more than 4152 molecules.
Therefore, given the breadth of the claims; the lack of guidance and working examples; the unpredictability in the art; and the state-of-the-art as discussed above, undue trial and error experimentation would be required to make and use the claimed invention, and therefore, the invention is not enabled throughout the broad scope of the claims.
Inadequate Written Description for Genus
Claims 1-13 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. All dependent claims are included in this rejection unless they include a limitation that overcomes the deficiencies of the parent claim.
Claim 1 is broadly drawn to a DNA molecule comprising a sequence with at least 85% identity to SEQ ID NO: 233 wherein the sequence is operably linked to a heterologous transcribable polynucleotide molecule.
Claim 4 depends from claim 1 an requires that “the DNA sequence comprises a regulatory element”, and this necessarily means that the genus of sequences encompassed by claim 1 includes sequences that both comprise a regulatory element and do NOT comprise a regulatory element. The Applicant defines a regulatory element as “a DNA molecule having gene regulatory activity” and defines “gene regulatory activity” as “the ability to affect the expression pattern of an operably linked transcribable polynucleotide molecule by affecting the transcription and/or translation of that operably linked transcribable polynucleotide molecule” (Spec 6). Therefore, claim 1 encompasses sequences that do not comprise the ability to affect the expression pattern of an operably linked transcribable polynucleotide molecule.
The Applicant describes analysis of genomic sequences from different plants, including Setaria italica, and identification of putative promoters, leaders, introns, and transit sequences (Id. 26) and putative introns (Id. 136-137). Applicant describes multiple sequences that are putative introns, including the claimed sequence of SEQ ID NO: 233 (Id. 137-139). Applicant discloses the relative expression level of the reporter protein, b-glucuronidase (GUS), in transient protoplast assays (Id. 137-139). The expression level is in comparison to a control intron. Table 22 (Spec 137-139) shows intron-mediated enhancement of GUS expression relative to I-Zm.DnaK-1:1:1 (Sequence ID NO: 1102). The expression level for the claimed intron (SEQ ID NO: 233) was a mean of 1.53 with standard deviation of 0.52 compared to the control that was designated as 1.0. It appears that all constructs utilized a CaMV 35S promoter with the different introns operably linked followed by the GUS coding sequence (Spec 136 and Fig. 15).
Applicant does not describe any sequences with at least 85% identity to SEQ ID NO: 233 or sequences that are fragments of SEQ ID NO: 233 that are purported to have any regulatory activity.
See, for example, Rose, A. B. (RNA (2002) Vol. 8; pp. 1444-1453) who teaches that deletions and mutations of nucleotides in an intron lost the ability to regulate the expression of a transgene (Rose 1444-1448). Rose teaches that none of the structural characteristics that are shared between the PAT1 intron and other dicot introns are essential for intron-mediated enhancer activity (Id. 1448). This shows that there is a high degree of unpredictability regarding which nucleotides within an intron are necessary for enhancer activity.
Part (c) of claim 1 does not include any minimum size for the claimed fragments, and part (a) allows for 15% of the nucleotides to be altered. SEQ ID NO: 233 is 1014 nucleotides in length, therefore the genus of molecules encompassed by claim 1 is more than 4152 molecules. Applicant has only reduced to practice one of the molecules encompassed by this genus, and that is the full length polynucleotide of SEQ ID NO: 233.
Given the breadth encompassed by the claims, and the lack of any description of motifs (structures) associated with regulatory activity, and the lack of a representative number of species within the claimed genus having been reduced to practice, the instant specification does not provide an adequate written description to support the breadth of the claims.
Indefiniteness
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 1-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. All dependent claims are included in this rejection unless they include a limitation that overcomes the deficiencies of the parent claim.
Claim 1 recites the limitation "wherein said sequence is operably linked to a heterologous transcribable polynucleotide molecule" in the last two lines. There is insufficient antecedent basis for this limitation in the claim. There is a sequence in the first line of the preamble and a sequence in part (a) and a sequence in part (b). There is no sequence recited in part (c). It is unclear if the heterologous transcribable polynucleotide must be linked to the DNA sequence from the preamble or if it is only required to be linked to the sequence in part (a) or part (b). Claims 2, 3, and 8 have the same issue. This indefinites can be overcome by amending the claims to clearly require the fragment in part (c) to be operably linked to a heterologous transcribable polynucleotide.
Failure to Further Limit
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 12 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 12 is directed to a progeny plant of the transgenic plant of claim 11, or a part thereof, wherein the progeny plant or part thereof comprises said DNA molecule. There is nothing in claim 12 to distinguish this progeny plant from the transgenic plant or part thereof that is claimed in claim 11. The two claims are identical in scope. Therefore, claim 12 does not further limit claim 11. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-3 and 8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claim(s) recite(s) a DNA molecule comprising a DNA sequence that is a fragment of SEQ ID NO: 233 that has gene regulatory activity and a transgenic plant cell comprising said construct. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because it is unclear if the fragment recited in part (c) of claim 1 and claim 8 is required to be operably linked to a heterologous transcribable polynucleotide molecule (see rejection for indefiniteness, above). If the fragment of SEQ ID NO: 233 is not required to be operably linked to a heterologous sequence, then this fragment is indistinguishable from native genomic DNA found in a Setaria italica plant. With regard to claim 8, the use of the adjective “transgenic” does not provide any required structure to distinguish the claimed plant cell from any Setaria italica plant cell, and the use of the term “DNA construct” does not amount to “significantly more” than the native genomic DNA in a Setaria italica plant unless particular structural elements in the DNA construct are required in the claim.
These rejections can be overcome by amending the claims to clearly require the fragment in part (c) to be operably linked to a heterologous transcribable polynucleotide.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claim(s) 1, 4, 8, 9, 11, and 12 is/are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Callis et al. ((1987) Genes and Development; Vol. 1; pp. 1183-1200) taken with the evidence of Yu et al. ((2003) GenBank Accession AY241178.1; p. 1) and Rose et al. ((2008) The Plant Cell; Vol. 20; pp. 543-551; referred to hereafter as “Rose2”).
Callis teaches multiple DNA constructs comprising the maize Adh1 intron operably linked to polynucleotides encoding reporter proteins (CAT and luciferase) (Callis, 1190, Figure 6). Yu teaches that nucleotides 95-100 of the ADH1 intron and nucleotides 202-207 of the ADH1 intron are “TCGATC”. Rose2 teaches the most common motif in high-scoring rice introns is T C/A G A/T T C/G (Rose2 548 Figure 3C). This shows that TCGATG is a known motif in introns that function as enhancers. The instant SEQ ID NO: 233 comprises this same motif (TCGATG) at nucleotides 261-266. Therefore, the DNA constructs taught by Callis that utilized the ADH1 intron comprise a fragment of SEQ ID NO: 233 that has gene regulatory activity and is operably linked to a heterologous transcribable polynucleotide (claims 1 and 4). The constructs were introduced into Black Mexican Sweet (BMS) maize cells (Callis 1184 and 1198) resulting in transgenic plant cells comprising these constructs (claim 8). Maize cells are monocot cells (claim 9). These maize cells are a “part” of a transgenic plant comprising the required DNA molecule (claims 11 and 12).
Summary
No claim is allowed.
Examiner’s Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHY KINGDON whose telephone number is (571)272-8784. The examiner can normally be reached M-F 9:00 - 5:30 EST.
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CATHY KINGDON
Primary Examiner
Art Unit 1662
/CATHY KINGDON/Primary Examiner, Art Unit 1662