DETAILED ACTION
Notice of 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 .
Election/Restrictions
Applicant's election with traverse Group I, claims 1 and 5-19, in the reply filed on 18 2025 is acknowledged. Applicant’s contend that the claims within Groups I-IV are linked so as to share a technical feature of modulating intracellular pressure of mammalian cells and organs and modulate transport of aqueous fluid and therapeutic molecules. It is asserted they are not deemed patentably distinct.
This is not deemed convincing given sharing a function/technical feature that is a function is not the criteria for applications filed under 37 C.F.R. 1.111(a). In addition, while the proteins may share a function, they do not share structures that fall within the scope of the claims. For example, SEQ ID NOs: 1 and 2 only share 37% sequence identity; SEQ ID NOs: 1 and 3 share 51.8% identity and SEQ ID NO: 1 and 4 share only 72.3% identity, which is not within the scope of Group I. Thus, it is clear the Groups are patently distinct from one another.
The requirement is still deemed proper and is therefore made FINAL.
Status of Application
Claims 1-37 are pending; claims 2-4 and 20-37 are withdrawn and claims 1 and 5-19 are subject to examination on the merits.
Priority
The instant application is a CIP of 17419878 (now US Patent 11548920) which is a 371 of PCT/US2019/068912 filed 30 December 2019 which claims benefit of US Provisional 62/786,955 filed 31 December 2018.
Claim Objections
Claim 1 is objected to because of the following informalities: the claim can be improved with respect to grammar in line five by reciting “when expressed on a mammalian cell membrane”; or alternatively, “when expressed on mammalian cell membranes”.
Claim 5 is objected to because of the following informalities: the claim can be improved with respect to grammar by deleting “of” before “SEQ ID NO:5”.
Claim 12 is objected to because of the following informalities: periods in claims are not permitted except at the end of the claim and when used for abbreviations (See MPEP 608.01(m)). Thus, it is suggested to replace, for example, “a.” with “(a)” or “a)”, and “b.” with “(b)” or “b)”.
Claims 6-19 are objected to because of the following informalities: the claims are dependent upon claim 1 which recites “mechanosensitive channel of large conductance 1 (MscL1) protein”. However, claims 6-19 only recite “wherein heterologous expressed mechanosensitive channels, its variants….” For consistency, it is suggested to recite “wherein the mechanosensitive channel large conductance 1 (MscL1) proteins”
Appropriate correction is required.
Claim 1 is objected to because of the following informalities: the claims are dependent upon claim 1 which recites “mechanosensitive channel of large conductance 1 (MscL1) protein and its generated sited directed mutant(s) thereof, wherein MscL1 protein or mutant(s) thereof comprises at least 75% sequence identity to SEQ ID NO: 1 and wherein the MscL1 protein or mutant(s) thereof, when….”.
For consistency, it would be more accurate to recite: “mechanosensitive channel of large conductance 1 (MscL1) protein and its generated sited directed mutant(s) thereof, wherein MscL1 protein or generated sited directed mutant(s) thereof comprises at least 75% sequence identity to SEQ ID NO: 1 and wherein the MscL1 protein or generated sited directed mutant(s) thereof, when…”
Claim Interpretation
Claims 6-19 recite various intended use of the claimed protein(s) of claim 1 it is noted, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2112.
Claim Rejections - 35 USC § 112(b)
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.
Claims 6-19 are rejected under 35 U.S.C. 112(b) second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1 recites the limitation "its variants" in reference to claim 1. There is insufficient antecedent basis for this limitation in the claim because claim 1 does not recite variants. Rather only generated site-directed mutant(s).
Claim Rejections - 35 USC § 112(d)
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.
Claims 6-19 are rejected under 35 U.S.C. 112(d) 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.
The claims are dependent upon claim 1, which recites a synthetic polypeptide sequence of a mechanosensitive channel of large conductance 1 (MscL1) protein and its generated site-directed mutants thereof comprises at least 75% sequence identity to SEQ ID NO: 1. However, claims 6-19 recite heterologously expresses mechanosensitive channels, variants and generated site-directed mutants. The claims are deemed broader because they are not limited to any particular mechanosensitive channel protein, variants of the any mechanosensitive protein and generated site-directed mutants of any of the proteins or variants of the proteins.
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 and 6-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a natural phenomenon) without additional elements that integrate the judicial exception into a practical application. An analysis with respect to the claims as a whole reveals that they do not include additional elements that integrate the judicial exception into a practical application. See MPEP 2106.
Analysis of subject-matter eligibility under 35 U.S.C. § 101 requires consideration of the following steps:
Step (1) whether the claim is directed to one of the four categories recited in §101 (process, machine, manufacture or composition of matter);
Step (Revised 2A - Prong 1) do the claims recite an abstract idea (mathematical concepts, mental processes or method of organizing human activity), law of nature or natural phenomenon;
Step (Revised 2A - Prong 2) do the claims recite additional elements that integrate the judicial exception into a practical application; and
Step (2B) whether the claim as a whole recites something that amounts to significantly more than the judicial exception. (See 2019 Revised Patent Subject Matter Eligibility Guidance (2019 PEG)).
Step 1: Yes; the claims are directed to a composition of matter.
Step 2A – Prong 1: Yes, the claims recite a natural phenomenon, namely, a naturally occurring product/protein.
Step 2A – Prong 2: No, the claims do not recite any additional elements that integrate the judicial exception into a practical application because the claims are merely drawn to what already exists in nature. As can be seen by the result in Supplemental Content, 20260108_120309_us-18-151-752-1.rup file, Result #1, a protein from Shigella dysenteriae WRSd3 having 85.8% sequence identity to instant SEQ ID NO: 1 exists in nature.
RESULT 1
A0A090NJ63_SHIDY
(NOTE: this sequence has 37 duplicates in the database searched.
See complete list at the end of this report)
ID A0A090NJ63_SHIDY Unreviewed; 136 AA.
AC A0A090NJ63;
DT 26-NOV-2014, integrated into UniProtKB/TrEMBL.
DT 26-NOV-2014, sequence version 1.
DT 18-JUN-2025, entry version 48.
DE RecName: Full=Large-conductance mechanosensitive channel {ECO:0000256|HAMAP-Rule:MF_00115};
GN Name=mscL {ECO:0000256|HAMAP-Rule:MF_00115};
GN ORFNames=WRSd3_01492 {ECO:0000313|EMBL:ESU80405.1};
OS Shigella dysenteriae WRSd3.
OC Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria;
OC Enterobacterales; Enterobacteriaceae; Shigella.
OX NCBI_TaxID=1401327 {ECO:0000313|EMBL:ESU80405.1, ECO:0000313|Proteomes:UP000017944};
RN [1] {ECO:0000313|EMBL:ESU80405.1, ECO:0000313|Proteomes:UP000017944}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=WRSd3 {ECO:0000313|EMBL:ESU80405.1,
RC ECO:0000313|Proteomes:UP000017944};
RA Aksomboon Vongsawan A., Venkatesan M.M., Vaisvil B., Emel G., Kepatral V.,
RA Sethabutr O., Serichantalergs O., Mason C.;
RT "Draft genomes and the virulence plasmids of Sd1617 vaccine constructs:
RT WRSd3 and WRSd5.";
RL Submitted (OCT-2013) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Channel that opens in response to stretch forces in the
CC membrane lipid bilayer. May participate in the regulation of osmotic
CC pressure changes within the cell. {ECO:0000256|HAMAP-Rule:MF_00115}.
CC -!- SUBUNIT: Homopentamer. {ECO:0000256|ARBA:ARBA00011255,
CC ECO:0000256|HAMAP-Rule:MF_00115}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000256|HAMAP-
CC Rule:MF_00115}; Multi-pass membrane protein {ECO:0000256|HAMAP-
CC Rule:MF_00115}. Cell membrane {ECO:0000256|ARBA:ARBA00004651}; Multi-
CC pass membrane protein {ECO:0000256|ARBA:ARBA00004651}.
CC -!- SIMILARITY: Belongs to the MscL family. {ECO:0000256|ARBA:ARBA00007254,
CC ECO:0000256|HAMAP-Rule:MF_00115}.
CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ
CC whole genome shotgun (WGS) entry which is preliminary data.
CC {ECO:0000313|EMBL:ESU80405.1}.
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DR EMBL; AXUT01000102; ESU80405.1; -; Genomic_DNA.
DR RefSeq; WP_000022442.1; NZ_AXUT01000102.1.
DR AlphaFoldDB; A0A090NJ63; -.
DR SMR; A0A090NJ63; -.
DR GeneID; 75173461; -.
DR PATRIC; fig|1401327.3.peg.1382; -.
DR Proteomes; UP000017944; Unassembled WGS sequence.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008381; F:mechanosensitive monoatomic ion channel activity; IEA:UniProtKB-UniRule.
DR FunFam; 1.10.1200.120:FF:000001; Large-conductance mechanosensitive channel; 1.
DR Gene3D; 1.10.1200.120; Large-conductance mechanosensitive channel, MscL, domain 1; 1.
DR HAMAP; MF_00115; MscL; 1.
DR InterPro; IPR019823; Mechanosensitive_channel_CS.
DR InterPro; IPR001185; MS_channel.
DR InterPro; IPR037673; MSC/AndL.
DR InterPro; IPR036019; MscL_channel.
DR NCBIfam; TIGR00220; mscL; 1.
DR NCBIfam; NF001841; PRK00567.1-1; 1.
DR NCBIfam; NF001843; PRK00567.1-4; 1.
DR PANTHER; PTHR30266:SF2; LARGE-CONDUCTANCE MECHANOSENSITIVE CHANNEL; 1.
DR PANTHER; PTHR30266; MECHANOSENSITIVE CHANNEL MSCL; 1.
DR Pfam; PF01741; MscL; 1.
DR PRINTS; PR01264; MECHCHANNEL.
DR SUPFAM; SSF81330; Gated mechanosensitive channel; 1.
DR PROSITE; PS01327; MSCL; 1.
PE 3: Inferred from homology;
KW Cell inner membrane {ECO:0000256|HAMAP-Rule:MF_00115};
KW Cell membrane {ECO:0000256|ARBA:ARBA00022475, ECO:0000256|HAMAP-
KW Rule:MF_00115};
KW Ion channel {ECO:0000256|ARBA:ARBA00023303, ECO:0000256|HAMAP-
KW Rule:MF_00115};
KW Ion transport {ECO:0000256|ARBA:ARBA00023065, ECO:0000256|HAMAP-
KW Rule:MF_00115};
KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|HAMAP-Rule:MF_00115};
KW Transmembrane {ECO:0000256|ARBA:ARBA00022692, ECO:0000256|HAMAP-
KW Rule:MF_00115};
KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989, ECO:0000256|HAMAP-
KW Rule:MF_00115};
KW Transport {ECO:0000256|ARBA:ARBA00022448, ECO:0000256|HAMAP-Rule:MF_00115}.
FT TRANSMEM 21..52
FT /note="Helical"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00115"
FT TRANSMEM 72..96
FT /note="Helical"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00115"
SQ SEQUENCE 136 AA; 14957 MW; 18EF7E1BD7DF9491 CRC64;
Query Match 85.8%; Score 668; Length 136;
Best Local Similarity 100.0%;
Matches 136; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 22 MSIIKEFREFAMRGNVVDLAVGVIIGAAFGKIVSSLVADIIMPPLGLLIGGIDFKQFAVT 81
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MSIIKEFREFAMRGNVVDLAVGVIIGAAFGKIVSSLVADIIMPPLGLLIGGIDFKQFAVT 60
Qy 82 LRDAQGDIPAVVMHYGVFIQNVFDFLIVAFAIFMAIKLINKLNRKKEEPAAAPAPTKEEV 141
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LRDAQGDIPAVVMHYGVFIQNVFDFLIVAFAIFMAIKLINKLNRKKEEPAAAPAPTKEEV 120
Qy 142 LLTEIRDLLKEQNNRS 157
||||||||||||||||
Db 121 LLTEIRDLLKEQNNRS 136
There is nothing in the claims which differentiates this naturally occurring protein in terms of structure and/or function because “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (MPEP 2112.01(II)). Thus, there is ultimately nothing in the claims which integrates the judicial exception into a practical application. Even for the which recite intended use of the proteins, there is nothing in the claims or specification which distinguishes that found in nature from that found in Shigella dysenteriae or E. coli (See Result #3, same file as above).
Step 2B: As noted in answering that of 2A – Prong 2 above, there is nothing in the claims which amounts to significantly more in terms of structure and/or function and the claims read on naturally occurring proteins. Thus, the claims are drawn to a judicial exception, namely, a naturally occurring product.
Claim Rejections - 35 USC § 112(a)
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 and 6-19 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.
The claims are drawn to mechanosensitive channel large conductance 1 (MscL1) proteins having at least 75% sequence identity to instant SEQ ID NO: 1, and generated site directed mutants thereof, wherein when said proteins are expressed in mammalian cell membranes, can sense pressure changes and modulate intracellular-pressure, or modulate molecular transport including aqueous fluids and therapeutic molecules, presumably meaning across the cell membrane. It is noted SEQ ID NO: 1 is drawn to a fusion protein comprising a 21 amino acid signal sequence comprising SEQ ID NO: 7, fused N-terminally to E. coli MscL1 protein and having amino acids 22-156 of SEQ ID NO: 1. Thus, the claims are drawn to a large and variable genus of MscL1 of SEQ ID NO: 1 having as little as 75% identity thereto and further, any of those polypeptides, having generated site-directed mutations. The specification, however, only discloses two specific site directed mutations, e.g. I113L/I70E substitutions (to avoid confusion with I and 1, this double substitution is Ile113Leu+Ile70Glu), which is SEQ ID NO: 5, or the single substitution Ile113Leu+Lys122Thr (SEQ ID NO: 6). The specification does disclose a wide variety of bacterial mechanosensitive channel proteins from E. coli, M. tuberculosis and V. cholera, having a wide array sequence identities - See below, e.g. M. tuberculosis (SEQ ID NO: 2) has 37% identity to instant E. coli SEQ ID NO: 1; V. cholera (SEQ ID NO: 4) has 72.3% identity to instant SEQ ID NO: 1 and which can function in the manner of controlling intra-cellular pressure as well as molecular transport of fluids across the membrane, the consistent thing between each of SEQ ID NO: 1, 2 and 4, despite the low sequence identity is they all have 100% sequence identity in the N-terminal signal sequence of SEQ ID NO: 7 (MLPQQVGFVCAVLALVCCASG). Thus, this presumably plays a significant role in the success of bacterial mechanosensitive large conductance proteins being capable of functioning as required across the mammalian cell membranes (e.g. in molecular delivery and osmotic/intracellular pressure control). However, there is no example of any site-directed generated mutants of the signal sequence which demonstrate the requisite functionality as claimed for those sequences having as little as 75% identity to instant SESQ ID NO: 1. Nor are there any other examples of site-directed generated mutations of SEQ ID NO: 1, not occurring in the signal sequence, outside Ile113Leu+Ile70Glu (SEQ ID NO: 5) and Ile113Leu+Lys122Thr (SEQ ID NO: 6), which demonstrate the requisite structure-function relationship required by the claims. These example are not representative of the large and variable genus as claimed in terms of structure and function.
M. tuberculosis (SEQ ID NO: 2) – 37% identity to instant SEQ ID NO: 1, but has 100% identity in N-terminal signal sequence N-terminal signal sequence, 21 amino acids (e.g. SEQ ID NO: 7 - MLPQQVGFVCAVLALVCCASG).
Run on: January 13, 2026, 09:27:23 ; Search time 1 Seconds
(without alignments)
0.027 Million cell updates/sec
Title: US-18-151-752-1
Perfect score: 779
Sequence: 1 MLPQQVGFVCAVLALVCCAS..........KEEVLLTEIRDLLKEQNNRS 157
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 172 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 1 summaries
Database : US-18-151-752-2.pep:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 288 37.0 172 1 US-18-151-752-2 Method, Compositio
ALIGNMENTS
RESULT 1
US-18-151-752-2
Query Match 37.0%; Score 288; DB 1; Length 172;
Best Local Similarity 44.8%;
Matches 74; Conservative 19; Mismatches 48; Indels 24; Gaps 6;
Qy 1 MLPQQVGFVCAVLALVCCASGMSIIKEFREFAMRGNVVDLAVGVIIGAAFGKIVSSLVAD 60
|||||||||||||||||||||| :| |:|| |||:||||| |:|| || :|:
Db 1 MLPQQVGFVCAVLALVCCASGM--LKGFKEFLARGNIVDLAVAVVIGTAFTALVTKFTDS 58
Qy 61 IIMPPLGLLIGGIDFKQFAVTLRDAQGDIPAVVMHYG--------VFIQNVFDFLIVAFA 112
|| | || | :|| |: : : | | : :| ::|||
Db 59 IITP----LINRIGV--------NAQSDVGILRIGIGGGQTIDLNVLLSAAINFFLIAFA 106
Qy 113 IFMAIKLINKLNRKKEEPAAAPAPTKEEVLLTEIRDLLKEQNNRS 157
:: : | ||| | | | : |||||||||| : | |
Db 107 VYFLVVLPYNTLRKKGE-VEQPGDT-QVVLLTEIRDLLAQTNGDS 149
V. cholera (SEQ ID NO: 4) – 72.3% identity to instant SEQ ID NO: 1, but has 100% identity in N-terminal signal sequence, 21 amino acids (e.g. SEQ ID NO: 7 - MLPQQVGFVCAVLALVCCASG).
Run on: January 13, 2026, 09:29:09 ; Search time 1 Seconds
(without alignments)
0.025 Million cell updates/sec
Title: US-18-151-752-1
Perfect score: 779
Sequence: 1 MLPQQVGFVCAVLALVCCAS..........KEEVLLTEIRDLLKEQNNRS 157
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 157 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 1 summaries
Database : US-18-151-752-4.pep:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 563.5 72.3 157 1 US-18-151-752-4 Method, Compositio
ALIGNMENTS
RESULT 1
US-18-151-752-4
Query Match 72.3%; Score 563.5; DB 1; Length 157;
Best Local Similarity 69.4%;
Matches 109; Conservative 22; Mismatches 25; Indels 1; Gaps 1;
Qy 1 MLPQQVGFVCAVLALVCCASGMSIIKEFREFAMRGNVVDLAVGVIIGAAFGKIVSSLVAD 60
|||||||||||||||||||||||::|||: || ||||:|:|||:|||||||||||| |||
Db 1 MLPQQVGFVCAVLALVCCASGMSLLKEFKAFASRGNVIDMAVGIIIGAAFGKIVSSFVAD 60
Qy 61 IIMPPLGLLIGGIDFKQFAVTLRDAQGDIPAVVMHYGVFIQNVFDFLIVAFAIFMAIKLI 120
|||||:|:::||::| : | |||| ||||: || ||| | || |:|||||| :| |
Db 61 IIMPPIGIILGGVNFSDLSFVLLAAQGDAPAVVIAYGKFIQTVVDFTIIAFAIFMGLKAI 120
Qy 121 NKLNRKKEE-PAAAPAPTKEEVLLTEIRDLLKEQNNR 156
| | ||:|| | | |||||:: ||:||||||| | ::
Db 121 NSLKRKEEEAPKAPPAPTKDQELLSEIRDLLKAQQDK 157
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1 and 6-19 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Walton & Gandhi (US 20120034619 – cited herein; hereafter Walton).
Walton teaches:
Regarding claims 1 and 6-19, an N-terminal His-tagged E. coli large mechanosensitive channel (MscL) protein, fused C-terminally to a superfold GFP protein, wherein said protein has 86.3% sequence identity to instant SEQ ID NO: 1 from amino acids 15-157 – See Figures 4B and 5 and Supplemental Content, 20260108_120309_us-18-151-752-1.rag file, Result #4 (reproduced below).
As noted in MPEP 2122.01(II): COMPOSITION CLAIMS — IF THE COMPOSITION IS PHYSICALLY THE SAME, IT MUST HAVE THE SAME PROPERTIES
“Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
With regard to the intended use of the proteins of claims 6-19, as noted above in the claim interpretation section, the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2112.
RESULT 4
AZT44975
ID AZT44975 standard; protein; 405 AA.
XX
AC AZT44975;
XX
DT 29-MAR-2012 (first entry)
XX
DE N-terminal poly-histidine tag comprising MscL-GFP protein #3.
XX
KW Mechanosensitive channel; MscL protein; fusion protein;
KW protein quantitation.
XX
OS Escherichia coli.
OS Chimeric.
OS Synthetic.
OS Unidentified.
XX
FH Key Location/Qualifiers
FT Protein 21..156
FT /note= "Large mechanosensitive channel (MscL) protein"
FT Region 157..166
FT /note= "TEV protease recognition site"
FT Cleavage-site 166..167
FT /note= "TEV cleavage site"
FT Protein 167..405
FT /note= "Superfolder green fluorescent protein (sGFP)"
XX
CC PN US2012034619-A1.
XX
CC PD 09-FEB-2012.
XX
CC PF 01-AUG-2011; 2011US-00195788.
XX
PR 30-JUL-2010; 2010US-0369601P.
XX
CC PA (WALT/) WALTON T.
CC PA (GAND/) GANDHI C.
XX
CC PI Walton T, Gandhi C;
XX
DR WPI; 2012-B80002/14.
XX
CC PT Counting proteins in a protein complex for determining its oligomeric
CC PT state involves tagging a protein of protein complex; expressing tagged
CC PT protein in culture; selectively digesting expressed tagged proteins with
CC PT a protease; and analyzing.
XX
CC PS Disclosure; Fig 5; 35pp; English.
XX
CC The invention relates to a novel method of counting proteins in a protein
CC complex and for determining the oligomeric state of an oligomeric protein
CC complex. The method involves: tagging a protein of the protein complex to
CC form a tagged protein comprising a peptide tag and a protease cleavage
CC site between the peptide tag and the protein; expressing the tagged
CC protein in a culture to form a tagged complex comprising expressed tagged
CC proteins; selectively digesting the expressed tagged proteins with a
CC protease to form an analyte mixture comprising selectively digested
CC proteins; and analyzing the analyte mixture at, at least two different
CC time points to quantify the selectively digested proteins. The method is
CC also used for membrane protein oligomer characterization. The methods of
CC counting protein subunits of an oligomeric complex are based on the
CC removal of mass and/or charge and are designed to be fast, reproducible
CC with modest amounts of protein, generalizable to membrane and soluble
CC proteins, and experimentally accessible to most protein laboratories.
CC This technique encompasses the removal of both mass and/or charge on
CC protein subunits of homo-oligomeric and hetero-oligomeric complexes. The
CC present sequence is a fusion protein comprising N-terminal poly-histidine
CC tag, Escherichia coli large mechanosensitive channel (MscL) protein, and
CC superfolder green fluorescent protein (sGFP), used in the invention for
CC determining the oligomeric state of MscL, channel complex.
XX
SQ Sequence 405 AA;
Query Match 86.3%; Score 672; Length 405;
Best Local Similarity 97.2%;
Matches 139; Conservative 0; Mismatches 4; Indels 0; Gaps 0;
Qy 15 LVCCASGMSIIKEFREFAMRGNVVDLAVGVIIGAAFGKIVSSLVADIIMPPLGLLIGGID 74
|| | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 14 LVPRGSHMSIIKEFREFAMRGNVVDLAVGVIIGAAFGKIVSSLVADIIMPPLGLLIGGID 73
Qy 75 FKQFAVTLRDAQGDIPAVVMHYGVFIQNVFDFLIVAFAIFMAIKLINKLNRKKEEPAAAP 134
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 74 FKQFAVTLRDAQGDIPAVVMHYGVFIQNVFDFLIVAFAIFMAIKLINKLNRKKEEPAAAP 133
Qy 135 APTKEEVLLTEIRDLLKEQNNRS 157
|||||||||||||||||||||||
Db 134 APTKEEVLLTEIRDLLKEQNNRS 156
Claim(s) 1 and 6-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Doerner et al. (Nat. Communications, 2012 – cited herein).
Doerner et al. teach E. coli mechanosensitive channel large conductance protein MscL which has been modified to be expressed in mammalian cells CHO, HEK-293 and HeLa. Said E. coli MscL proteins are taught comprising both wild-type and a variant MscL protein with a G26C substitution which further comprises FLAG tag of DYKDDDDL inserted after Ile68, both of which are expressed in mammalian cells. The resultant wild-type protein has 85.8% identity to instant SEQ ID NO: 1 and the variant protein has 82.8% identity to instant SEQ ID NO: 1 (See Methods, cDNA construct and Cell lines and transfection). The resultant sequence alignment is generated below. Given the protein are taught as explicitly expressed in mammalian cells, then they would be capable of all of the intended uses as stipulated in claims 6-19.
Wild-type MscL (Db) vs instant SEQ ID NO: 1 (Qy)
GenCore version 6.5.2
Copyright (c) 1993 - 2026 Biocceleration Ltd.
OM protein - protein search, using sw model
Run on: January 13, 2026, 11:38:09 ; Search time 1 Seconds
(without alignments)
0.021 Million cell updates/sec
Title: US-18-151-752-1
Perfect score: 779
Sequence: 1 MLPQQVGFVCAVLALVCCAS..........KEEVLLTEIRDLLKEQNNRS 157
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 136 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 1 summaries
Database : AASEQ2_01132026_113806.pep:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 668 85.8 136 1 AASEQ2_01132026_113806
ALIGNMENTS
RESULT 1
AASEQ2_01132026_113806
Query Match 85.8%; Score 668; DB 1; Length 136;
Best Local Similarity 100.0%;
Matches 136; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 22 MSIIKEFREFAMRGNVVDLAVGVIIGAAFGKIVSSLVADIIMPPLGLLIGGIDFKQFAVT 81
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MSIIKEFREFAMRGNVVDLAVGVIIGAAFGKIVSSLVADIIMPPLGLLIGGIDFKQFAVT 60
Qy 82 LRDAQGDIPAVVMHYGVFIQNVFDFLIVAFAIFMAIKLINKLNRKKEEPAAAPAPTKEEV 141
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LRDAQGDIPAVVMHYGVFIQNVFDFLIVAFAIFMAIKLINKLNRKKEEPAAAPAPTKEEV 120
Qy 142 LLTEIRDLLKEQNNRS 157
||||||||||||||||
Db 121 LLTEIRDLLKEQNNRS 136
G26C and Flag-tagged MscL (Db) vs instant SEQ ID NO: 1 (Qy)
GenCore version 6.5.2
Copyright (c) 1993 - 2026 Biocceleration Ltd.
OM protein - protein search, using sw model
Run on: January 13, 2026, 11:27:06 ; Search time 1 Seconds
(without alignments)
0.023 Million cell updates/sec
Title: US-18-151-752-1
Perfect score: 779
Sequence: 1 MLPQQVGFVCAVLALVCCAS..........KEEVLLTEIRDLLKEQNNRS 157
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 144 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 1 summaries
Database : AASEQ2_01132026_112703.pep:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 645 82.8 144 1 AASEQ2_01132026_112703
ALIGNMENTS
RESULT 1
AASEQ2_01132026_112703
Query Match 82.8%; Score 645; DB 1; Length 144;
Best Local Similarity 93.8%;
Matches 135; Conservative 0; Mismatches 1; Indels 8; Gaps 1;
Qy 22 MSIIKEFREFAMRGNVVDLAVGVIIGAAFGKIVSSLVADIIMPPLGLLIGGIDFKQFAVT 81
||||||||||||||||||||||||| ||||||||||||||||||||||||||||||||||
Db 1 MSIIKEFREFAMRGNVVDLAVGVIICAAFGKIVSSLVADIIMPPLGLLIGGIDFKQFAVT 60
Qy 82 LRDAQGDI--------PAVVMHYGVFIQNVFDFLIVAFAIFMAIKLINKLNRKKEEPAAA 133
|||||||| ||||||||||||||||||||||||||||||||||||||||||||
Db 61 LRDAQGDIDYKDDDDKPAVVMHYGVFIQNVFDFLIVAFAIFMAIKLINKLNRKKEEPAAA 120
Qy 134 PAPTKEEVLLTEIRDLLKEQNNRS 157
||||||||||||||||||||||||
Db 121 PAPTKEEVLLTEIRDLLKEQNNRS 144
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 and 5-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11548920. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘920 patent anticipate the instant claims.
The instant claims in their broadest are drawn to a synthetic polypeptide sequence of a mechanosensitive channel of large conductance 1 (MscL1) protein and its generated site-directed mutant(s) thereof, wherein said MscL1 or mutant(s) thereof comprises at least 75% sequence identity to SEQ ID NO:1 and wherein the MscL1 protein or mutant(s) thereof, when expressed on mammalian cell membrane, senses pressure changes and modulates the intra-cellular pressure, or molecular transport including aqueous fluid and therapeutic molecules. Dependent claims are drawn to specific sequences of SEQ ID NO: 5 (Ile113Leu+Ile70Glu) or 6 (Ile113Leu+Lys122Thr) (claim 5); and intended use of the MscL1 proteins (claim 6-19).
The claims to the ‘920 patent in their broadest are drawn to a synthetic polypeptide sequence of a mechanosensitive channel of large conductance 1 (MscL1) protein and its generated site-directed mutant(s) thereof, wherein said MscL1 or mutant(s) thereof comprises at least 95% sequence identity to SEQ ID NO:1 and wherein the MscL1 protein or mutant(s) thereof, when expressed on mammalian cell membrane, senses pressure changes and modulates the intra-cellular pressure, or molecular transport including aqueous fluid and therapeutic molecules. Dependent claims recite the polypeptide has a I to L substitution at position 113 (claim 24); and dependent claims 4-23 recite intended uses of the claimed proteins.
Thus, the difference between the two sets of claims is the percent identity to SEQ ID NO: 1, wherein the claims to the ‘920 recite 95% identity to SEQ ID NO: 1. This, however, still falls within the scope of the instant percent identity of SEQ ID NO: 1 of at least 75% and thus necessarily anticipates the instant claims.
Anticipation Analysis MPEP 804(II)(B)(2):
“The claim under examination is not patentably distinct from the reference claim(s) if the claim under examination is anticipated by the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 1052, 29 USPQ2d 2010, 2015-16 (Fed. Cir. 1993). This type of nonstatutory double patenting situation arises when the claim being examined is, for example, generic to a species or sub-genus claimed in a conflicting patent or application, i.e., the entire scope of the reference claim falls within the scope of the examined claim.”
Conclusion
No claim is allowed.
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/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 13 January 2026