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
1. Applicant’s election of Group I (claims 1-16 & 23) in the reply filed on 6/19/26 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
2. Claims withdrawn:
Claims 17, 21 & 22 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
3. Priority
Applicant’s claim for domestic priority under 35 U.S.C. 119(e), filed 6/15/23, is acknowledged.
4. Drawings
The drawings filed on 7/25/25 are acknowledged.
5. Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant's cooperation is requested in correcting any errors of which applicant may become aware in the specification.
6. Drawings filed 6/14/24 is acknowledged.
7. IDS filed 7/25/25 is acknowledged. A signed copy of the IDS is provided with this Office Action.
8. Written Description
Claims 1-16 & 23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, as containing 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(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-16 & 23 of the instant application are directed to the following genus claims.
1. A recombinant microorganism comprising one or more modifications with respect to a corresponding microorganism not comprising the one or more modifications, wherein the one or more modifications comprise a recombinant orf14 gene encoding an Orf14 protein comprising an amino acid sequence of Orf14 of Limosilactobacillus reuteri (SEQ ID NO:2), Orf14 of Limosilactobacillus mucosae (SEQ ID NO:4), or Orf14 of Limosilactobacillus oris (SEQ ID NO: 6), or an amino acid sequence of a homolog of any of the foregoing.
2. The recombinant microorganism of claim 1, wherein the Orf14 protein comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO:2, SEQ ID NO: 4, or SEQ ID NO:6.
3. The recombinant microorganism of claim 1, wherein the Orf14 protein comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO:2, SEQ ID NO:4, or SEQ ID NO:6.
4. The recombinant microorganism of claim 1, wherein the recombinant orf14 gene comprises a promoter and a coding sequence, wherein the promoter is heterologous to the coding sequence.
5. The recombinant microorganism of claim 1, wherein the recombinant microorganism is a bacterium.
6. The recombinant microorganism of claim 1, wherein the recombinant microorganism is commensal to human gastrointestinal tract.
7. The recombinant microorganism of claim 1, wherein the recombinant microorganism comprises a glycerol dehydratase.
8. The recombinant microorganism of claim 1, wherein the recombinant microorganism comprises a propanediol utilization gene set.
9. The recombinant microorganism of claim 1, wherein the recombinant microorganism and the corresponding microorganism produce reuterin.
10. The recombinant microorganism of claim 1, wherein the recombinant microorganism exhibits enhanced production of reuterin with respect to the corresponding microorganism.
11. The recombinant microorganism of claim 1, wherein the recombinant microorganism is from a genus selected from the group consisting of Anaerobutyricum, Bacillus, Blautia Citrobacter, Clostridium, Enterobacter, Enterococcus, Flavonifractor, Klebsiella, Lactobacillus, Limosilactobacillus, Listeria, Pediococcus, Salmonella, Streptococcus, Terrisporobacter, and Yersina.
12. The recombinant microorganism of claim 1, wherein the recombinant microorganism is L. reuteri.
13. The recombinant microorganism of claim 1, wherein the recombinant microorganism comprises an inactivation of at least one biologically active prophage present in the corresponding microorganism.
14. The recombinant microorganism of claim 13, wherein the recombinant microorganism is L. reuteri and comprises an inactivation of at least one of Φ1 and Φ2.
15. The recombinant microorganism of claim 1, wherein the recombinant microorganism comprises an inactivation of each biologically active prophage present in the corresponding microorganism.
16. The recombinant microorganism of claim 15, wherein the recombinant microorganism is L. reuteri and comprises an inactivation of each of Φ1 and Φ2.
23. The recombinant microorganism of claim 1, wherein: the Orf14 protein comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO:2, SEQ ID NO:4, or SEQ ID NO:6; the recombinant orf14 gene comprises a promoter and a coding sequence, wherein the promoter is heterologous to the coding sequence; the recombinant microorganism is L. reuteri and comprises an inactivation of each of Φ1 and Φ2; and the recombinant microorganism exhibits enhanced production of reuterin with respect to the corresponding microorganism.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. For a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
“A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus.”). Regents of the University of California v. Eli Lilly & Co., 119, F.3d 1559, 1568, 43 USPQ2d 1398, 1405 (Fed. Cir. 1997).
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the biomolecule, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule.”
“The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice …, reduction to drawings …, or 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 function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.” MPEP 2163.
Furthermore, a “‘representative number of species’ means that the species which are adequately described are representative of the entire 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 disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure ‘indicates that the patentee has invented species sufficient to constitute the gen[us].’ See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (‘[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.’). ‘A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.’ In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).” MPEP 2163.
In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, the Court of Appeals for the Federal Circuit has held that “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials”. As indicated in MPEP § 2163, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or 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 function and structure, or by a combination of such identifying characteristics, sufficient to show that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that a representative number of species means that the species which are adequately described are representative of the entire 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 factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163.
In the instant case, there is no structure associated with function with regard to the members of genus of – “A recombinant microorganism comprising one or more modifications with respect to a corresponding microorganism not comprising the one or more modifications, wherein the one or more modifications comprise a recombinant orf14 gene encoding an Orf14 protein comprising an amino acid sequence of Orf14 of Limosilactobacillus reuteri (SEQ ID NO:2), Orf14 of Limosilactobacillus mucosae (SEQ ID NO:4), or Orf14 of Limosilactobacillus oris (SEQ ID NO: 6), or an amino acid sequence of a homolog of any of the foregoing.”
The claim recites “one or more modifications comprise a recombinant orf14 gene encoding an Orf14 protein comprising an amino acid sequence of Orf14 of Limosilactobacillus reuteri (SEQ ID NO:2), …SEQ ID NO: 4 or SEQ ID NO: 6; wherein “an amino acid sequence of SEQ ID NO: 2, for example, may be interpreted to be a fragment of SEQ ID NO: 2 of any size, and further with no assigned function. No fragments are described. No homolog are disclosed nor a sequence search revealed to existed of homologs.
No information, beyond the characterization of: A recombinant microorganism transformed with a orf14 gene encoding an Orf14 protein, wherein the Orf14 protein comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 2, SEQ ID NO: 4, or SEQ ID NO: 6; the orf14 gene comprises a promoter and a coding sequence, wherein the promoter is heterologous to the coding sequence; the recombinant microorganism is L. reuteri and comprises an inactivation of each of Φ1 and Φ2; and the recombinant microorganism exhibits enhanced production of reuterin as compared to a microorganism not transformed with the said genes; has been provided by the applicants’, which would indicate that they had possession of the claimed genus of recombinant hosts comprising a genus of polypeptides with the associated function and encoding polynucleotides
The genus of polypeptides and the encoding polynucleotides required in the claimed invention is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of polypeptides is adequately described by the disclosure of the structures of SEQ ID NO: 2, 4 or 6, with specific structures having the associated function/activity, since one could use structural homology to isolate those polypeptides and the encoding polynucleotides recited in the claims. The art clearly teaches the “Practical Limits of Function Prediction”:
(a) Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and (iv) conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that “Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105). Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105). Applicants’ are respectfully directed to the problems associated EC Classification in the section “Transferring the EC Classification enzyme to Non-Enzyme Comparisons”; pages 101-102 and Fig. 2a)-b), highlighting the structural and functional heterogeneity based on EC Classification numbers; as the stereo-specificity, substrate-specificity and catalytic properties vary widely.
(b) Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340) also highlight the difficulties associated with “Prediction of protein function from protein sequence and structure”; “To reason from sequence and structure to function is to step onto much shakier ground”, closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer (page 309, paragraph 4), it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given three protein functions, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions (page 312, paragraph 5), in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity (page 313, paragraph 4), although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein’s role fundamentally (page 323, paragraph 1).
(c) This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polynucleotides and encoded polypeptides do not necessarily share the same function. For example, Witkowski et al., (Biochemistry 38:11643-11650, 1999), teaches that one conservative amino acid substitution transforms a b-ketoacyl synthase into a malonyl decarboxylase and completely eliminates b-ketoacyl synthase activity.
AS stated above no information, beyond the characterization of: A recombinant microorganism transformed with a orf14 gene encoding an Orf14 protein, wherein the Orf14 protein comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 2, SEQ ID NO: 4, or SEQ ID NO: 6; the orf14 gene comprises a promoter and a coding sequence, wherein the promoter is heterologous to the coding sequence; the recombinant microorganism is L. reuteri and comprises an inactivation of each of Φ1 and Φ2; and the recombinant microorganism exhibits enhanced production of reuterin as compared to a microorganism not transformed with the said genes; has been provided by the applicants’, which would indicate that they had possession of the claimed genus of recombinant hosts comprising a genus of polypeptides with the associated function and encoding polynucleotides, which would indicate that they had possession of the claimed genus of polypeptides and the encoding polynucleotides. As the claimed genera of polypeptides having widely variable structures and associated function, since minor changes in structure may result in changes affecting function and no additional information (species/variant/mutant) correlating structure with function has been provided. Furthermore, “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” (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895).
Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. Applicants are referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
9. Claim Rejections - 35 USC § 112 (second paragraph)
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 1-16 & 23 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 1 for example recites – “A recombinant microorganism comprising one or more modifications with respect to a corresponding microorganism not comprising the one or more modifications, wherein the one or more modifications comprise a recombinant orf14 gene encoding an Orf14 protein comprising an amino acid sequence of Orf14 of Limosilactobacillus reuteri (SEQ ID NO:2), Orf14 of Limosilactobacillus mucosae (SEQ ID NO:4), or Orf14 of Limosilactobacillus oris (SEQ ID NO: 6), or an amino acid sequence of a homolog of any of the foregoing.”
The claim is unclear about the language use for comparing the recombinant microorganism with a unmodified microorganism or control with specific modification given.
Following is suggestion to overcome the rejection:
A recombinant microorganism transformed with a orf14 gene encoding an Orf14 protein, wherein the Orf14 protein comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 2, SEQ ID NO: 4, or SEQ ID NO: 6; the orf14 gene comprises a promoter and a coding sequence, wherein the promoter is heterologous to the coding sequence; the recombinant microorganism is L. reuteri and comprises an inactivation of each of Φ1 and Φ2; and the recombinant microorganism exhibits enhanced production of reuterin as compared to a microorganism not transformed with the said genes.
Claims 2-16 & 23 are included in the rejection for failing to correct the defect present in the base claim(s).
10. No claim is allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to TEKCHAND SAIDHA whose telephone number is (571)272-0940. The examiner can normally be reached on M-F 8.00-5.30. 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, Robert B Mondesi can be reached on 408 918 7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TEKCHAND SAIDHA/
Primary Examiner, Art Unit 1652
Recombinant Enzymes, Hoteling
Telephone: (571) 272-0940
Fax: (571) 273-0940
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