Prosecution Insights
Last updated: April 19, 2026
Application No. 17/758,477

COMPOSITIONS AND METHODS FOR AUTO-INDUCIBLE CELLULAR LYSIS AND NUCLEOTIDE HYDROLYSIS

Non-Final OA §103§112
Filed
Jul 07, 2022
Examiner
MONSHIPOURI, MARYAM
Art Unit
1651
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Duke University
OA Round
1 (Non-Final)
79%
Grant Probability
Favorable
1-2
OA Rounds
2y 3m
To Grant
99%
With Interview

Examiner Intelligence

Grants 79% — above average
79%
Career Allow Rate
756 granted / 956 resolved
+19.1% vs TC avg
Strong +37% interview lift
Without
With
+37.3%
Interview Lift
resolved cases with interview
Typical timeline
2y 3m
Avg Prosecution
28 currently pending
Career history
984
Total Applications
across all art units

Statute-Specific Performance

§101
2.9%
-37.1% vs TC avg
§103
23.9%
-16.1% vs TC avg
§102
17.2%
-22.8% vs TC avg
§112
36.3%
-3.7% vs TC avg
Black line = Tech Center average estimate • Based on career data from 956 resolved cases

Office Action

§103 §112
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 . Applicant’s response to restriction requirement filed 11/25/25 is acknowledged. Applicant elected the following species :Group 2, claims 11-12, drawn to a method of cellular lysis and recovery of a heterologous protein product and Group (i), a method of use of λ phage. In view of applicant’s amendment, the restriction between Groups IIIA-IIIB is hereby withdrawn. Claims 1, 3-10, 17, 20 are withdrawn as drawn to non-elected subject matter. Claim 2 is canceled. DETAILED ACTION Claims 11-16, 18, 19 are under examination on the merits. Specification The specification is objected for reciting hyperlink language (see for example page 20, [0082], line 11). Applicant is advised to delete hyperlink language everywhere in the disclosure in compliance with 37 CFR section 1.57(d). 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 11-16, 18 and 19 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. Claim 11 (and its dependent claims 12-16, 18, 19) are directed to a generic method using a genus of periplasmic lysozyme genes and a genus of cytoplasmic nuclease genes, in E. coli, under a generic promoter, wherein said genera have been inadequately described in the disclosure in terms of structure. The court of Appeals for the Federal Circuit has recently held that such a general definition does not meet the requirements of 35 U.S.C. 112, first paragraph. “ A written description of an invention involving chemical genus, like a description of a chemical species, requires a precise definition, such as be 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., 1997 U.S. App. LEXIS 18221, at *23, quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). The court held that “ in claims involving chemical materials, generic formulae usually indicate with specificity what generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. accordingly, such a formula is normally an adequate description of the claimed genus. In claims to genetic material, however, a generic statement such as “vertebrate insulin cDNA” or “mammalian insulin cDNA,’ without more, is not an adequate written description of the genus because it does not distinguish it from others. One skilled in the art therefore cannot, as one can do with a fully described genus visualize the identity of the members of the genus”. Here, applicant is claiming a genus of periplasmic lysozyme encoding genes and cytoplasmic nuclease encoding genes and a genus of promoters that induce their expression by nutrient depletion by what they do rather than what they structurally are and this kind of description fails to satisfy the requirements of 112 first paragraph. Regarding said genera of periplasmic lysozyme genes applicant has merely provided 2 species namely, Lambda phage, benzonase encoding genes, which is totally inadequate to fully represent the structural requirement of the genus claimed. This problem also exits with the genus of cytoplasmic nucleases, which is merely represented by a single species, namely nucA from Serratia marcescens, which is totally inadequate to fully characterize said genus. In addition, applicant has failed to explain which specific inducible promoters or operons beyond yibDp promoter (a single species) are utilized for expressing one or more periplasmic lysozyme encoding genes and one or more cytoplasmic nuclease encoding genes. The disclosure merely refers to operons that merely comprise either periplasmic lysozyme encoding genes or nuclease encoding genes. Applicant is advised to refer the examiner to where in the disclosure an operon in which both periplasmic lysozymes encoding genes and nuclease encoding genes are incorporated. Therefore, based on the information provided in the disclosure one of skill in the art cannot reasonably conclude that applicant had full possession of this invention, before the effective filing of this application. 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. Claim 13 is 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. The dependent claim 13, does seem to be further limiting than its base claim 11. Claim Rejections - 35 USC § 103 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. Claim(s) 11-16, 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Jia et al., “Jia” (US2006/0040393, 2/2006). Jia teaches about engineered E. coli strains that are capable of rapid controlled lysis or herein "autolysis" (see abstract). The XJa E. coli strains were made from JM109 and the XJb strains from BL21 by insertion of the λ R or (λ RS) lytic endolysin gene (which is both a periplasmic lysozyme and a nuclease encoding gene) to replace the tightly regulated araB gene. Thus, arabinose becomes a non-metabolizable inducer and the controlled autolysis phenotype is induced by the PBAD promoter by the presence of saturating arabinose. Upon induction of the bacteriophage λR endolysin, the E. coli remains intact but is efficiently lysed after one freeze-thaw cycle (see instant claim 15). Jia also mentions that said E. coli is useful for routine protein expression (see abstract). In [0020], Jia teaches that in representative cultures, about 75% or more of all cells, expressing λR endolysin, were lysed after one freeze-thaw cycle. The ability to be lysed remained high starting at about 4 hours after induction with arabinose, or from logarithmic growth for approximately 20 additional hours, which is well into stationary phase growth (see instant claim 14). This corresponds to growth stages where E. coli strains are typically harvested for production of recombinant protein. In Example 7, Triton X-100 (which is a non-ionic detergent ) added to after induced cell lysis and it was found that the presence of low amounts of such detergents can increase the efficiency of the autolysis further (see instant claim 16). Considering instant claim 12, Jia in Example 4 recites that some strains were lysogenized using a commercially available λ phage (DE3) method to introduce the T7 RNA polymerase system, for use in the expression of recombinant proteins and said additional stains are preferred embodiments that couple the autolysis of the bacteria to a well-studied protein expression system. In Example 5, Jia discloses that cultures of XJa (DE3) or JM109 (DE3) expressing a His-tagged β-galactosidase (which is a heterologous protein) from a pet-based plasmid were grown overnight in commercially available EB/OB (expression broth/overexpression broth) media supplemented with about 0.2% arabinose, 1 mM MgCl.sub.2 according to the manufacturer’s instructions. The EB/OB media system provides convenient protein expression from the T7-lac promoter by regulating levels of cyclic AMP (cAMP) and cAMP receptor protein. Protein expression is repressed in EB media followed by high level expression in OB media. Therefore, it is believed that the teachings of Jia as a whole, render this invention obvious. No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARYAM MONSHIPOURI whose telephone number is (571)272-0932. The examiner can normally be reached full-flex. 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, Melenie L Gordon can be reached at 571-272-8037. 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. /MARYAM MONSHIPOURI/Primary Examiner, Art Unit 1651
Read full office action

Prosecution Timeline

Jul 07, 2022
Application Filed
Jan 05, 2026
Non-Final Rejection — §103, §112 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
79%
Grant Probability
99%
With Interview (+37.3%)
2y 3m
Median Time to Grant
Low
PTA Risk
Based on 956 resolved cases by this examiner. Grant probability derived from career allow rate.

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