DETAILED ACTION
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 Election/Restriction Filed, Amendment, and Arguments/Remarks, filed 13 November 2025, have been entered. Claims 1-6, 10, 12-21, 27, 29-30, and 48 are currently pending. Claims 1, 30, and 48 are independent claims. Applicant’s election of the invention of Group I, drawn to a synthetic therapeutic bacteriophage and a live biotherapeutic, is acknowledged.
Additionally, Applicant’s election of the following species:
therapeutic agents: a. a binding protein;
binding protein activities: c. inhibits an immune checkpoint molecule: i. Immune checkpoint molecules: 6. PD-L1;
in a reply filed 13 November 2025 is acknowledged. While Applicant has not indicated whether these elections of the invention of Group I and species of binding protein which inhibits PD-L1 have been made with or without traverse, Applicant has not provided any arguments traversing the restriction/election requirement(s). Therefore, the elections of the invention of Group I and species of binding protein which inhibits the immune checkpoint molecule PD-L1 are considered to have been made without traverse.
Claim 48 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 13-16, 19, 21, 27, and 29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 1-6, 10, 12, 17-18, 20, and 30 are currently pending in the application and under examination to which the following grounds of rejection are applicable. An action on the merits follows.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/CA2021/051415, filed 07 October 2021, which claims priority to U.S. Provisional Application Nos. 63/088,643, filed 07 October 2020, 63/161,543, filed 16 March 2021, and 63/215,176, filed 25 June 2021. Thus, the earliest possible priority for the instant application is 07 October 2020.
Information Disclosure Statement
The information disclosure statements filed 05 April 2023, 25 July 2024, 28 May 2025, 17 September 2025, and 06 February 2026 have been considered by the Examiner. Examiner notes the filing of IDS Size Fee assertions for the IDSs filed 28 May 2025, 17 September 2025, and 06 February 2026, as required under 37 CFR 1.98, indicating that no IDS size fee is required under 37 CFR 1.17(v) at this time.
Specification
The disclosure is objected to because of the following informalities: the Brief Description of the Drawings recites, “Figures 14A-14H” in [0036]. However, Figure 14 only has panels A to C. Appropriate correction is required.
The use of the term “Gemzar” in [00125], “EZ10-Spin Column Plasmid Miniprep” in [00146], “QIAGEN Plasmid Maxi Kit” in [00146], “TransStart FastPFU fly DNA polymerase” in [00146] and [00166], “NEBuilder HiFi DNA Assembly Master Mix” in [00146], “Agencourt Ampure XP DNA binding beads” in [00147], “Zymoclean Gel DNA Recovery Kit” in [00147], “Phage Titration ELISA kit” in [00162], [00177], [00196], [00200], “Chelex” in [00166], “EvaGreen” in [00166], “BD Accouri C6 Plus” in [00167], “Amicon Ultra-15 10kDa Centrifugal Filter Unit” in [00183], “Immobilon ECL Ultra Western HRP” in [00197], “Vilber Fusion FX” in [00197], which are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Note that the specification has not been inspected sufficiently to identify all uses of trade names and/or marks used in commerce. It is Applicant’s responsibility to ensure complete compliance.
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.
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 18 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.
Claim 18 recites, “the immune checkpoint molecule is selected from”, which is indefinite because it is unclear whether the list of checkpoint molecules is an open or a closed group. As such, the metes and bounds of the claim cannot be determined.
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.
Claim(s) 1-2, 12, 17-18, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kalim et al. 2019, Cytotechnology, 71(3), 705-722, IDS.
Regarding claim 1, note that the term “displaying” in line 1 has been interpreted to encompass any attachment of a therapeutic agent to a coat protein in any orientation or position.
Kalim discloses a synthetic therapeutic bacteriophage displaying at least one therapeutic agent, wherein the therapeutic agent is an inhibitory anti-PD-L1 scFV (as elected), wherein the at least one therapeutic agent is fused to a coating/coat protein of the synthetic bacteriophage [abstract, column 15 ¶ 2, Figure 1].
Regarding claim 2, Kalim discloses wherein the synthetic therapeutic bacteriophage is a filamentous bacteriophage/ a phage comprising filaments [column 6 ¶ 1].
Regarding claims 12, 17-18, and 20, Kalim teaches wherein the therapeutic agent is a PD-L1 binding protein which produces an antitumoral activity by binding to and inhibiting the PD-L1 immune checkpoint molecule [abstract, column 3 ¶ 1, column 27 ¶ 1, Figure 1].
Accordingly, by teaching all of the limitations of claims 1-2, 12, 17-18, and 20, Kalim anticipates the instant invention as claimed.
Claim Rejections - 35 USC § 102/103
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 3-6, 10, and 30 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Kalim et al. [2019, Cytotechnology, 71(3), 705-722, IDS]; as evidenced by and/or in view of Hess & Jewel [2019, Bioengineering & Translation Medicine, 5, e10142, 1-15] and Mai-Prochnow et al. [2015, FEMS Microbiology Reviews, 39, 465-487].
Regarding claim 1, note that the term “displaying” in line 1 has been interpreted to encompass any attachment of a therapeutic agent to a coat protein in any orientation or position.
Kalim discloses a synthetic therapeutic bacteriophage displaying at least one therapeutic agent, wherein the therapeutic agent is an inhibitory anti-PD-L1 scFV (as elected), wherein the at least one therapeutic agent is fused to a coating/coat protein of the synthetic bacteriophage [abstract, column 15 ¶ 2, Figure 1].
Regarding claim 3, note that “bacteriophage secretion system comprising a bacteriophage machinery” has been interpreted to encompass a system facilitating the secretion of the bacteriophage itself or any molecule produced by the bacteriophage, wherein at least one component encoded by the bacteriophage genome contributes to the secretion of the bacteriophage and/or molecule.
Kalim teaches the production of bacteriophage using an E. coli host [column 2 ¶ 1, column 4 ¶ 1], including the amplification of phage using host bacterial cells [column 4 ¶ 2]. Kalim also suggests that the filamentous phage is an M13 phage in that Kalim uses an anti-M13 antibody to detect the bound bacteriophages [column 9 ¶ 1].
Kalim does not explicitly disclose wherein the synthetic therapeutic bacteriophage comprises a bacteriophage secretion system comprising a bacteriophage machinery. However, Hess teaches that filamentous phages used for phage display therapeutics, such as M13 and fd, comprise a bacteriophage secretion system comprising bacteriophage machinery, including a bacteriophage genome encoding coat proteins, wherein progeny bacteriophage are secreted by progeny genomes exiting the cell envelope and thereby acquiring coat proteins [column 6 ¶ 1].
Therefore, given the teachings of Kalim that the synthetic M13 filamentous bacteriophage are produced and amplified in a bacterial host and the teachings of Hess that filamentous M13 bacteriophage comprise a secretion system that allows for the secretion of the bacteriophage from the host cell, an ordinarily skilled artisan would expect that the synthetic bacteriophage of Kalim inherently comprises such secretion genes/system, or, alternatively, an ordinarily skilled artisan would be motivated to include such modules for the propagation of the bacteriophage in a bacterial host cell.
“When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent.” See MPEP 2112.01 or In re Best, 195 USPQ 430, 433 (CCPA 1997). Further, reliance upon inherency is not improper even though a rejection is based on Section 103 instead of Section 102. In re Skoner, et al. 186 USPQ 80 (CCPA). As stated in MPEP 2112, the express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 102 or 103. "The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness." In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995). See also In re Grasselli, 713 F.2d 731,739, 218 USPQ 769, 775 (Fed. Cir. 1983). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).
Regarding claims 4-6, note that “module” has been interpreted to encompass at least one gene and/or at least one factor contributing to the indicated function for assembly, replication, coating, or therapeutic activity. As discussed above, Kalim teaches a synthetic filamentous therapeutic bacteriophage displaying at least one therapeutic agent which is an anti-PD-L1 scFv (as elected), wherein the at least one therapeutic agent is genetically fused to a coat/coating protein of the synthetic bacteriophage [abstract, column 6 ¶ 1, column 15 ¶ 2, column 31 ¶ 2, Figure 1, 8]. Therefore, Kalim teaches that the synthetic bacteriophage comprises a therapeutic module comprising the at least one therapeutic agent to be displayed by the synthetic therapeutic bacteriophage and a coating protein.
Hess teaches that the filamentous bacteriophage M13 and fd strain genomes encodes coat proteins, including pIII, pVI, pVII, pVIII, and pIX, each of which can be fused to a peptide or a protein to efficiently display the peptide or protein on the phage surface, and as such, Hess teaches wherein the bacteriophage machinery comprises a bacteriophage coating module and a bacteriophage therapeutic module, wherein the therapeutic module comprises one or more bacteriophage coating genes selected from gpIII, gpVI gpVII, gpVIII and gpIX encoding pIII, pVI, pVII, pVIII, and pIX [column 6 ¶ 1].
Additionally, Mai-Prochnow teaches that filamentous phage genomes, including class I Ff phages M13, f1, and fd, comprise a bacteriophage assembly module with a pI gene encoding G1P virion assembly-export protein, a pIV gene encoding a G4P virion assembly-export protein, and a pXI gene encoding G1P virion assembly-export protein; a bacteriophage replication module with a pII gene encoding G2P replication protein, a pV gene encoding a G5P DBA binding protein, and a pX gene encoding G10P replication-associated protein; and a bacteriophage coating module with pVI, pVII, pVIII, pIX genes encoding minor virion proteins and major capsid protein [column 3 ¶ 1, column 4 ¶ 1, Table 1, Figure 1, 2].
Therefore, given the teachings by Hess and Mai-Prochnow of the filamentous bacteriophage genes required for bacteriophage propagation and secretion from a host cell, and the genes which can be fused to a therapeutic agent for phage-display based delivery of the therapeutic, an ordinarily skilled artisan would expect that the synthetic bacteriophage of Kalim inherently comprises such genes/modules or, alternatively, an ordinarily skilled artisan would be motivated to include such modules for the propagation of the bacteriophage in a bacterial host cell to generate the synthetic bacteriophage displaying at least one therapeutic agent fused to a coating protein.
Regarding claim 10, Mai-Prochnow teaches that several filamentous prophages carry transcriptional repressors with various phage-specific functions [column 13 ¶ 4], and that the filamentous phage Pf1 has promoter sequences controlling expression of the bacteriophage genes, such as at the 5’ end of gene VIII, which can be regulated by trans factors such as Ntr [column 26 ¶ 2]. Mai-Prochnow teaches that a strategy deregulating phage gene expression in such a way that it results in decreased virulence, growth inhibition, and/or killing of the host may be utilized to engineer filamentous phage for application in therapy of diseases caused by bacteria [column 30 ¶ 4], thereby teaching motivation to manipulate the expression levels of the bacteriophage genes by alternating the regulatory sequences controlling bacteriophage gene expression. Therefore, given the teachings of Mai-Prochnow that filamentous bacteriophage genomes both encode transcriptional repressors and comprise promoters for regulating the expression of bacteriophage genes/machinery, such that the promoters comprise regulatory elements which respond to trans regulatory factors, an ordinarily skilled artisan would expect that the synthetic bacteriophage of Kalim inherently comprises such regulatory sequences/modules including regulatable promoters or, alternatively, an ordinarily skilled artisan would be motivated to include such regulatory sequences/modules to manipulate the expression/activity levels of the bacteriophage genes/machinery.
Regarding claim 30, Kalim teaches a recombinant E. coli host cells used to produce the synthetic therapeutic bacteriophages, wherein the recombinant E. coli comprise a bacteriophage secretion system capable of secreting the synthetic therapeutic bacteriophage as described above, i.e., the recombinant formation and soluble expression by E. coli host machinery such that high-affinity phages were amplified by using host bacterial cells [column 2 ¶ 1, column 4 ¶ 2, Figure 1]. Given the teachings of Hess and Mai-Prochnow of the genetic components contributing to the assembly, replication, coating, and secretion of filamentous M13 bacteriophage and the teachings of Hess to fuse a therapeutic agent to any of the pIII, pVI, pVII, pVIII, and pIX coat proteins; an ordinarily skilled artisan would expect the M13 bacteriophage of Kalim to inherently comprise a bacteriophage secretion system as recited in claims 3-6, 10, and 30. Accordingly, by teaching all of the limitations of claims 1, 3-6, 10, and 30, Kalim anticipates the instant invention as claimed.
Alternatively, given the motivations taught by Hess and Mai-Prochnow to include such modules for the propagation of the bacteriophage in a bacterial host cell to generate the synthetic bacteriophage displaying at least one therapeutic agent fused to a coating protein and to include regulatory sequences/modules including transcriptional repressors and/or regulatable promoters to manipulate the expression/activity levels of the bacteriophage genes/machinery for therapeutic application; it would have been prima facie obvious to an ordinarily skilled artisan at the time of filing the instant application to modify the synthetic bacteriophage and live biotherapeutic of Kalim to comprise a bacteriophage secretion system comprising a bacteriophage assembly module, a bacteriophage replication module, a bacteriophage coating module, and a bacteriophage therapeutic module as claimed with a reasonable expectation of success.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. KATIE L PENNINGTON whose telephone number is (703)756-4622. The examiner can normally be reached M-Th 8:30 am - 5:30 pm, Friday 8:30 am - 12:30 pm CT.
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, Maria G. Leavitt can be reached on (571) 272-1085. 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.
DR. KATIE L. PENNINGTON
Examiner
Art Unit 1634
/KATIE L PENNINGTON/Examiner, Art Unit 1634
Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634