DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-20 are pending.
Claims 3, 9, 10,15-16 and 18 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/16/2025.
Claims 1-2, 4-8, 11-14, 17 and 19-20 are examined herein.
Improper Markush Grouping
Claims 1, 7, and 17 remain and new claims 19 and 20 are rejected on the basis that they contain an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush groupings of the claims are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: The groupings are directed to diverse bacterial strains/species identified by the strain/species name and SEQ IDs setting forth a 16S rRNA sequence. Upon reviewing the art and the instant disclosure, it is reasonable to conclude that each of these bacteria has a distinct mode of conferring a beneficial trait and distinct structure with respect to the organism’s genome and encoded protein content. As such the members of the group do not share a “single structural similarity” and common use.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Response to Remarks
Applicant argues that the rejection to the claims on the basis that they contain an improper Markush group should be withdrawn because all of the species listed belong to the same art-recognized class – microbial endophytes. Applicant cites the MPEP for the premise that the members of an art-recognized class share a single structural similarity that is related to a common use. (Remarks p. 1-12). Applicant points to data showing that the seven strains listed in the claims confer fungal disease tolerance. (Table 1a).
This is not found persuasive. The MPEP clearly provides that “a recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved.” MPEP 2117. The bacteria listed in the claims represent bacteria from two different kingdoms of bacteria and several classes within the two kingdoms. As such, the claim that the array of genetically disparate bacterial stains in the claims are members of an art-recognized class appears to be unsupported by the facts. The only commonality of the disparate species is a shared ecological niche. Further, Applicant’s data (see Table 1a) shows that the different strains produce different effects in inoculated plants. As such one of ordinary skill in the art would not expect that the same intended result would be achieved.
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.
Claims 1-2, 4-8, 10, 11-14 and 17 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 Federal Circuit has clarified the written description requirement. The court stated that a written description of an invention "requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials". University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568; 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). The court also concluded that "naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not description of that material". Id. Further, the court held that to adequately describe a claimed genus, Patent Owner must describe a representative number of the species of the claimed genus, and that one of skill in the art should be able to "visualize or recognize the identity of the members of the genus". Id.
Applicant claims a method of improving a plant phenotype, comprising inoculating a plant element with a formulation comprising one or more biologically pure Bacillus spp., Curtobacterium ssp., Pseudomonas ssp, Achromobacter ssp, Pantoea ssp,. or Enterobacter ssp. endophyte strains isolated from Thespesia populnea and Gossypium hirsutum which are heterologously disposed to said plant element, wherein said endophyte strains are present in the formulation in an amount capable of modulating a trait of agronomic importance in a plant comprising or derived from said plant element, as compared to a reference plant grown under the same conditions, and a synthetic combination comprising, a plant element and a formulation comprising one or more biologically pure Bacillus spp., Curtobacterium ssp., Pseudomonas ssp, Achromobacter ssp, Pantoea ssp,. or Enterobacter ssp. endophyte strains isolated from Thespesia populnea and Gossypium hirsutuma, wherein said endophyte strains are present in the formulation in an amount capable of modulating a trait of agronomic importance in the plant comprising or derived from said plant element, as compared to a reference plant grown under the same conditions.
Applicant describes methods of isolating endophytic bacteria from wild cotton and Thespesia populnea plants grown in pots, identifying the bacteria by sequencing 16S rRNA coding sequences and characterizing some of the metabolic characteristics of the bacteria (ability to secrete proteases, solubilize phosphates, fix nitrogen and produce IAA) and their effects on plant growth and other agronomically useful characteristics. (Specification p. 75-86, Table 1A). Applicant describes the effects of inoculation of cotton plants with the Bacillus amyloliquefaciens strain Bamy on gene expression. (p. 87-112). Applicant describes detailed effects of the inhibitory effects of the deposited endophyte strains and extracts thereof on growth of a variety of fungi. (p. 113-130). Applicant describes the effects of inoculation of various seedlings with the deposited strains on different aspects of growth vigor. (p. 134-138). Applicant describes the effects of inoculating wheat plants with Pseudomonas oleovorans strain Poryz on yield in filed conditions and the effects on greenhouse grown corn, cotton and soybean. (p. 138-141, 144-145). Applicant describes the effects of inoculation of soy, cotton and corn plants with various deposited strains on tolerance to soil fungal pathogens and yield in field conditions (p. 146-149).
Applicant does not describe the genera of strains and combinations thereof that can produce the functions as required by the claims. The claims encompass methods and compositions comprising any combinations of any strains of the listed bacterial species. The limitations that the strains comprise 16S rRNA coding sequences having 97% identity to the listed sequence identifiers is expected to identify the species of bacteria, but given the high degree of conservation of 16S rRNA sequences, the limitation is not reliable in distinguishing strains that would produce the required functions from those that would not. Lan et al. (Microbiome 4.1 (2016): 1-13) teaches that the 16S rRNA sequence is widely used to identify bacterial species but is too conserved to be useful in distinguishing between closely related varieties. Further, the limitation that the bacteria are isolated from Thespesia populnea or Gossypium hirsutum does not describe the genera. Gaiero et al. (American journal of botany 100.9 (2013): 1738-1750 teaches that many factors such as environmental factors, plant growth stage, plant health and other microbes in the microbiome will affect the capacity of individual species to colonize a plant. As such, there would be no reasonable expectation that bacterial strains of the listed species collected from plants in pots grown in the conditions used by Applicant would be the same as strains collected from other Thespesia populnea or Gossypium hirsutum plants from different locations under different conditions. The other strains as encompassed by the claims have no description in the art and the instant disclosure fails to remedy this deficiency. Although Applicant has described a small number of specific strains, the strains described by Applicant are insufficient to describe the recited genera of combinations in view of the lack of any description of a structure-function relationship between the strains and recited functions.
Hence, Applicant has not, in fact, described the claimed inventions within the full scope of the claims, and the specification fails to provide an adequate written description of the claimed invention.
Response to Remarks
Applicant urges that the rejection under 35 USC 112a for failure to satisfy the written description requirement should be withdrawn because information need not be provided in the Specification when well-known in the prior art. Applicant first generically asserts that 16srRNA can be used to create genetic phylogenies and that the phylogenetic relatedness is also correlated to metagenomic and functional relatedness. Applicant cites Langille et al. in support of this proposition. Applicant points to the teachings of Langille:
"Phylogenetic trees based on 16S closely resemble clusters obtained based on shared gene content, and researchers often infer properties of uncultured organisms from cultured relatives."
Recently, some 16S studies have extended these intuitions to infer the functional contribution of particular community members by mapping a subset of abundant 16S sequences to their nearest sequenced reference genome.
Langille et al. set out to confirm the above correlation using a novel predictive modeling approach, PICRUSt, which "uses evolutionary modeling to predict metagenomes from 16S data and a reference genome database" to investigate, amongst other things, "the rate of decay of the phylogeny-function correlation".
Our results demonstrate that phylogeny and function are sufficiently linked that this 'predictive metagenomic' approach should provide useful insights into the thousands of uncultivated microbial communities for which only marker gene surveys are currently available.
The application of PICRUSt to diverse metagenomic data sets shows that the phylogenetic information contained in 16S marker gene sequences is sufficiently well correlated with genomic content to yield accurate predictions when related reference genomes are available ... .it can predict and compare probable functions across many samples from a wide range of habitats .... and provides functional insights into the tens of thousands of existing samples for which only 16S data are available.
Applicant argues that the teachings of Langille show that one of ordinary skill in the art could have, at the time of filing, used the 16s sequences and results demonstrated by Applicant related to the 7 described strains, to determine which bacteria having at least 97% identity to would function as required by the claims – improving a plant phenotype. (Remarks p. 12-15).
This is not found persuasive. Langille is silent as to how much variation in 16s sequences is tolerated to predict shared functionality and whether the predictability extends to producing specific agronomic benefits across different plant species. Applicant claims bacteria by virtue of comprising a 16s rRNA coding sequence having at least 97% identity to one provided in the sequence listing. It is initially noted, however, that even at 100% identity, the 16s rRNA sequence fails to distinguish different strains and species of bacteria in the types of bacteria that are the subject of the instant invention. For example, Enterobacter cloacae from cotton, Enterobacter kobei from tobacco and Pantoea agglomerans all comprise 16S rRNA sequences sharing 100% identity to the instant SEQ ID NO:17.
Langille also teaches that PICRUSt’s ability to detect patterns also depends on the input data used. The software cannot distinguish variation at the strain level if the marker gene sequence used is identical among strains, and it cannot detect gene families (or summarize them into pathways) if those genes are not included in the input genomic data used, or if pathway annotations are currently poor (e.g., for acetogenesis genes). (p. 820 right col. ¶ 2). As such, it is reasonable to conclude that systems like PICRUSt are ineffective in instances where the markers (here 16S rRNA sequences) are shared across species and that in order for systems like PICRUSt to operate, multiple data points must exist comprising 16s rRNA data correlated to phenotypes and functionality. There is no evidence that such data exists for the 16S rRNA sequences recited in the claims as they relate to plant improvements. Indeed, if Applicant had provided a dataset comprising related strains with multiple data points across the 97% range for each of the recited sequences, it would not only be reasonable to expect that a PICRUSt system could be used, but it might be sufficient to be deemed to adequately describe the claimed genera by virtue of example without any other showing. Here, no such data is presented.
Claims 19 and 20 are deemed to recite genera that are adequately described. At 99% identity, some variation across the recited strains is accounted for and this level of identity appears to at least encompass very closely related strains and species.
Claims 1-2, 4-8, 10, 11-14, 17 and 19-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as containing 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. Since the endophyte strains used in the claimed invention is essential to the claimed invention, it must be obtainable by a reproducible method set forth in the specification or otherwise be readily available to the public. If a strain is not so obtainable or available, a deposit thereof may satisfy the requirements of 35 U.S.C. 112. The specification does not disclose a reproducible process to obtain the exact same bacterial strain in each occurrence and it is not apparent if such a strain is readily available to the public. If the deposit of the strain is made under the terms of the Budapest Treaty, then an affidavit or declaration by the Applicant, or a statement by an attorney of record over his or her signature and registration number, stating the strain have been deposited under the Budapest Treaty and that the strain will be irrevocably, and without restriction or condition, released to the public upon the issuance of a patent would satisfy the deposit requirement made herein.
If the deposit has not been made under the Budapest Treaty, then in order to certify that the deposit meets the criteria set forth in 37 CFR 1.801-1.809, Applicant may provide assurance of compliance by an affidavit or declaration, or by a statement by an attorney of record over his or her signature and registration number showing that
(a) during the pendency of the application, access to the invention will be afforded to the Commissioner upon request;
(b) all restrictions upon availability to the public will be irrevocably removed upon granting of the patent;
(c) the deposit will be maintained in a public depository for a period of 30 years or 5 years after the last request or for the enforceable life of the patent, whichever is longer;
(d) the viability of the biological material at the time of deposit will be tested (see 37 CFR 1.807); and
(e) the deposit will be replaced if it should ever become unviable.
It is noted that Applicant indicates that the strains have been deposited in Page 4 of the instant Specification, with the exception of Pseudomonas oleovorans strain Poryz. Applicant has NOT indicated that the deposits have been made in accordance with 37 CFR 1.801-1.809. Accordingly, Applicant needs to provide a signed statement indicating compliance with 37 CFR 1.801-1.809, the ATCC Accession No. and evidence of deposit to overcome this rejection.
Response to Remarks
Applicant urges that the rejection to the claims under 35 USC 112(a) for failure to satisfy the enablement requirement because one of ordinary skill in the art could isolate strains satisfying the requirements of the claims by isolating strains and sequencing the 16S rRNA sequences without undue experimentation. Applicant cites to the various Wands factors in support of this basic premise, arguing that the technology to do so is routine and that in view of the teachings of the art such as those of Langille as discussed previously herein. (Remarks p. 15-18).
This is not found persuasive. Applicant recites specific strains in the claims that are reasonably interpreted to be required by the claims. Because, as noted previously herein, at even 100% identity, 16S rRNA sequences cannot reliably distinguish strains from one another. As such, whether strains with 16S rRNA sequences that share 100% identity to the recited sequence identifiers can be isolated is not material to whether the required strains are enabled without access to a deposit. As set forth previously herein deposits that satisfy the enablement requirement must comply with certain provisions. A statement from Applicant that the deposit requirements are satisfied would obviate the rejection.
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 1-2, 4-8, 11-14, 17 and 19-20 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 1, 7, 17, 19 and 20 recite the broad recitation of a bacterial species and the claim also recites a specific strain in a parenthetical, which is the narrower statement of the range/limitation. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Dependent claims are deemed indefinite by virtue of their dependency without clarifying the issue of indefiniteness.
Conclusion
No claims are allowed.
The claims appear to be free of the prior art. The prior art does not disclose, teach or otherwise render obvious using the recited strains in a synthetic application to a plant. The closest prior art is von Maltzahn et al. (US 20150373993 A1), which discloses the application of the same species as some of those recited in the claims, with high sequence identities to those listed, but von Maltzahn does not disclose or teach the specific strains that are recited in the claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHARLES A LOGSDON whose telephone number is (571)270-0282. The examiner can normally be reached M-F 8:30 - 5:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Shubo (Joe) Zhou can be reached at (571)272-0724. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHARLES LOGSDON/Primary Examiner, Art Unit 1662
Prosecution Insights