Prosecution Insights
Last updated: April 19, 2026
Application No. 17/744,136

METHODS AND SYSTEMS FOR GENERATING BIOLOGICAL MOLECULES

Non-Final OA §102§103§112
Filed
May 13, 2022
Examiner
CONSTANTINE, CHARLES Z
Art Unit
1657
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Machine Bio Inc.
OA Round
1 (Non-Final)
58%
Grant Probability
Moderate
1-2
OA Rounds
3y 4m
To Grant
99%
With Interview

Examiner Intelligence

Grants 58% of resolved cases
58%
Career Allow Rate
246 granted / 421 resolved
-1.6% vs TC avg
Strong +49% interview lift
Without
With
+49.3%
Interview Lift
resolved cases with interview
Typical timeline
3y 4m
Avg Prosecution
20 currently pending
Career history
441
Total Applications
across all art units

Statute-Specific Performance

§101
5.3%
-34.7% vs TC avg
§103
31.2%
-8.8% vs TC avg
§102
20.1%
-19.9% vs TC avg
§112
27.7%
-12.3% vs TC avg
Black line = Tech Center average estimate • Based on career data from 421 resolved cases

Office Action

§102 §103 §112
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. Response to Amendment The amendment received on 10/08/2025 is acknowledged. Claims 2-4 and 7 have been canceled. Claims 57-59 have been added. Claims 1, 8-20, 47-48 and 57-59 are currently pending. Election/Restrictions Applicant’s election without traverse of the invention of Group I, claims 1 , 7-20, and 57-59 and the species of Group B (subsequent to forming) , claims 1, 8-9, 11, 13-18, 20 and 57-59 in the reply filed on 10/08/2025 is acknowledged. Claims 47-48 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/08/2025. Claims 10, 12, and 19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 10/08/2025. Claims 1, 7-9, 11, 13-18, 20, and 57-59, have been treated on the merits. Claim Objections Claim 20 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 11 . When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). 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 appl icant regards as his invention. Claim 1, 7-9, 11, 13-18, 20, and 57-59 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. Regarding claim 1 and claims dependent there, it is unclear what applicant is claiming as it is unclear how or when the biological material is being formed. No step of synthesis of addition of a catalyst for forming a product is being added. It is further unclear how or when the product is being formed as in dependent claim 17, “the precursors do not comprise said biological molecule”, and claim 17 further limitation claim 1, this would suggest that the biological product may be present and not generated at all. Absent steps which make clear how products are being generated, it is unclear what applicant is claiming. The courts have indicated that before claimed subject matter can properly be compared to the prior art, it is essential to know what the claims do in fact cover. See, e.g., the following decisions: In re Steele, 305 F 2d. 859, 134 USPQ 292 (CCPA 1962); In re Moore 439 F 2d. 1232, 169 USPQ 236 (CCPA 1969); In re Merat, 519 F 2d. 1390, 186 USPQ 471 (CCPA 1975). Regarding claim 15 and the limitation “ wherein said pore of said membrane has a cross section that is at least 25 nm and at most 1,000 nm ”, it is unclear what applicant is claiming as cross-section typically refers to a 2-D area defining the shape/opening. The units used however aren’t 2 dimensional units, i.e. squared. It is unclear if applicant intended to claim that the cross section was “nm 2 ”, or if applicant intended to claim some other measurement to define the pores such as diameter or width which might use a unit of “nm”. Regarding claim 59 the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is unclear if the “ preferably wherein said one or more translocon proteins is SecYEG ” is required to be a part of the limitation . It would provide clarity to put preferred embodiment in dependent claims. Claim Rejections - 35 USC § 102 The following is a quotation of the appropriate paragraphs of 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 – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale , or otherwise available to the public before the effective filing date of the claimed invention. Claim(s) (a)(1) is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Peters ( USPGPub 20080287656/IDS submitted) . Regarding claim 1 and the limitation “” A method for generating a biological molecule, comprising: providing a chamber comprising a first portion, a second portion, and a membrane disposed between said first portion and said second port ion introducing a plurality of cell-free precursors of said biological molecule into said first portion translocating at least a portion of said biological molecule through said membrane, wherein said membrane comprises a pore and a lipid bilayer supported on said membrane and traversing said pore in said membrane, said lipid bilayer comprising one or more translocon proteins positioned above said pore in said membrane and configured to allow said biological molecule to be formed from at least a subset of said plurality of cell-free precursors ” Peters teaches devices for cell free synthesis of polypeptides and proteins ([0001]), and teaches the device has first portion or zone called cis zone and a second portion or zone called a trans zone connected by pores (Abstract, [0011]-[0025]), the pores are contain ed within a support body (90), which separates the zones and may be a sheet made of plastic, silicone, metal, ([0046]-[0052]) , these sheets can be considered a membrane . Peters teaches that the pores may contain a lipid bilayer membrane which further contains translocon /translocase protein system ([0020] -[ 0023], Claims 1-23) . Peters teaches that a polypeptide product may be generated using cell free protein synthesis ([0004] -[ 0024], [0041], Claim 1). And that the precursors required for synthesis are provided to the cis zone ([0017] , [0019], [0040] -[ 0053] ). Peters teaches that the produces proteins which ha ve the appropriate sequence are translocated though the translocation system (Abstract, [0014] -[ 0016]) Regarding claim 1 and the limitation “ and to be translocated through the membrane, said lipid bilayer further comprising one or more signal peptidase proteins configured to release said biological molecule from the membrane subsequent to translocation through the pore and into said second portion; ” Peters discloses that the translocated protein is usually cleaved by signal peptidases and thus discloses embodiments in which signal peptidases cleave tranlocated protein ([0054]). Regarding claim 1 and the limitation “ A nd collecting said biological molecule from said second portion. ” Peters teaches that the produced protein may be collected in the trans region either in a closed container or flowthrough system design ([0023] -[ 0024]). Regarding claim s 8 and 9 and the limitation s “ wherein said biological molecule further comprises an N-terminal translocation signal sequence ”, and “ wherein, after said biological molecule is translocated, said N-terminal translocation signal sequence is removed from said biological molecule by said signal peptidase. ”, Peters teaches the signal sequence may be amino or N-terminal and that the signal peptides are usually cleaved ([0054]) . Regarding claim s 11 and 20, and the limitation “ wherein said translocating occurs subsequently to said forming said biological molecule. ”, and “ , wherein said translocating of said biological molecule occurs subsequent to said forming of said biological molecule. ”, Peters teaches that after synthesis, the protein may be translocated to the trans zone ([0017])and teaches that the protein synthesis may occur prior to translocation ([0040], [0053]). Regarding claims 13 and 14 and the limitations “ wherein said biological molecule is a polypeptide ”, and “ wherein said polypeptide is a protein, and wherein at least a portion of said protein is folded in said second portion. ” Peters discloses the system for protein synthesis and teaches that folding may occur following translocation ([0014], [0040], [0055]). Regarding claim 15 and the limitation “ wherein said pore of said membrane has a cross section that is at least 25 nm and at most 1,000 nm ” , Peters discloses that the pores have diameters up to 500 nm ([0052]), and that they should be at least 15 nm ([0045]). The range of Peters includes ~50% of the claimed range, and the claimer range includes nearly the entirety of the range disclosed by Peters. Regarding claim 16 and the limitation “ wherein said chamber is a part of a flow channel ”, Peters discloses that the system may be designed for continuous-flow ([0008], [0024]). And further discloses embodiments in which reactant and products are flowed through the chamber (Figure 5, [0060]). Such arrangements can be considered to be a flow channel. Regarding claim 17 and the limitation “ wherein said cell-free precursors do not comprise said biological molecule ” Peters teaches that all of the components for cell free protein synthesis may be added to the cis zone, and teaches that the synthesis may occur right in the pores ([0053], [0056]). As the components for synthesis are being added, they do not comprise the molecule yet. Regarding claim 18 and the limitation “ wherein said translocating of said biological molecule comprises translocating of an entirety of said biological molecule through said pore and into said second portion ” Peters discloses embodiments in which the protein is translocated, embodiments in which the signal peptide is cleave, and embodiments in which the protein is membrane bound ([0014], [0028], [0040], [0054] -[ 0056]). Peters thus discloses embodiments in which the entire protein is translocated. Regarding claim 57 and the limitation “ wherein said providing step comprises providing a porous membrane, applying a solution comprising a plurality of proteoliposomes , wherein said plurality of proteoliposomes comprise a lipid bilayer and one or more translocon proteins, and reacting said plurality of proteoliposomes with said porous membrane to form said lipid bilayer on said porous membrane, wherein said lipid bilayer comprises said one or more translocon proteins. ”, Peters discloses that the translocation proteins may be in a liposome having a lipid bilayer and these liposome bound to the pores of the support which may be a membrane ([0047]-[0053]). Regarding claim 59 and the limitation “ wherein said one or more translocon proteins comprise one or more proteins selected from the group consisting of SecYEG , SecY , SecE , SecG , Sec61p, and an injectosome, preferably wherein said one or more translocon proteins is SecYEG . ” Peters teaches the use of Sec61 and specifically Sec61p ([0044] -[ 0045]-[0060], Claims 7-8). The above reference thus anticipates the claims. Claim Rejections - 35 USC § 103 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. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness . Claim 58 is rejected under 35 U.S.C. 103 as being unpatentable over Peters as applied to claim s 1, 7-9, 11, 13-18, 20, 57 , and 59 above, and further in view of Nierhaus ( USPGPub 20080187963) . Regarding claim 58 and the limitation “wherein said one or more signal peptidase proteins comprises LepA or LepB .” Peters does not teach the use of the specific signal peptidase LepA in the cell free protein synthesis system. This difference however would have been obvious to one of ordinary skill in the art as it’s use is taught in the same field of endeavor as cell free protein translational/synthesis systems by Nierhaus . In the same field of endeavor Nierhaus teaches the use of LepA as a signal peptidase in cell free protein synthesis ([0011], [0024] -[ 0033]). One of ordinary skill in the art would have found it obvious that LepA would be used as the signal peptidase in the system of Peters, as Peters teaches the use of this type of enzyme, and LepA is known to be used for cell free protein synthesis. One of ordinary skill in the art would be motivated to do so to use a peptidase which hydrolyzed the desired signal peptide of a desired protein product. One of ordinary skill in the art would further have a reasonable expectation of success in doing so as Nierhaus teaches the use of the enzyme for protein synthesis. Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT CHARLES Z CONSTANTINE whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-5533 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Mon-Fri 9-5 . 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, FILLIN "SPE Name?" \* MERGEFORMAT Louise Humphrey can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-272-5543 . 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 Z CONSTANTINE/ Examiner, Art Unit 1657
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Prosecution Timeline

May 13, 2022
Application Filed
Mar 07, 2026
Non-Final Rejection — §102, §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
58%
Grant Probability
99%
With Interview (+49.3%)
3y 4m
Median Time to Grant
Low
PTA Risk
Based on 421 resolved cases by this examiner. Grant probability derived from career allow rate.

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