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
The amendment filed on 12-23-2025 is acknowledged. Claims 20-22, 25, 30, 34-35, 37-41, 43-44, 52 and 55-62 have been amended. Claim 1 has been canceled. Claim 63 has been added. Claims 20-22, 25, 30, 34-35, 37-41, 43-44, 52 and 54-63 are pending. Claims 20-22, 25, 30, 34 and 54 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 35, 37-41, 43-44, 52 and 55-63 are currently under examination.
Information Disclosure Statement
The Information Disclosure Statements filed on 12-23-2025 and 3-20-2026 have been considered. Initialed copies are attached hereto.
It should be noted that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections Withdrawn
The objection to claim 35 for being dependent on non-elected claims is withdrawn in light of the amendment thereto.
The objection to claim 44 for reciting claim language drawn to non-elected inventions is withdrawn in light of the amendment thereto.
The objection to claim 55 for reciting claim language drawn to non-elected inventions is withdrawn in light of the amendment thereto.
The objection to claim 57 for reciting the phrase "genus of Table 6" is withdrawn in light of the amendment thereto.
The objection to claim 57 for reciting claim language drawn to non-elected inventions is withdrawn in light of the amendment thereto.
Claim Rejections Maintained
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 35, 37-41, 43-44, 52 and 55-63 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 for the reasons set forth in the previous Office action in the rejection of claims 35, 37-41, 43-44, 52 and 55-62. 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.
Applicant argues:
1. Applicant has amended the pending claims to replace the term "ADAS" with the term “minicell." The Examples of the present application provide clear and detailed methods for manufacturing bacterial minicells comprising a T3SS that is capable of delivering the cargo to a target cell; see, e.g., Example 1.
Applicant’s arguments have been fully considered and deemed non-persuasive.
With regard to Point 1, the amendment is insufficient to overcome the rejection. Minicells are disclosed in the specification of being a subset of ADAS and are not specifically disclosed in any Examples. Moreover, the specification clearly sets forth that the disclosure of ADASs with a heterologous T3SS is limited to strains of Escherichia coli overexpressing a heterologous T3SS captured from the virulence plasmid of Shigella flexneri (see page 34, lines 25-28). This limited disclosure cannot be extrapolated to the claimed genus of minicells.
The rejected claims are drawn to minicells derived from a parent bacterial cell, the minicell comprising a bacterial Type 3 secretion system (T3SS) that is heterologous to the parent bacterial. Additionally the minicell further require a cargo (polypeptide) which is deliverable to a target cell (claims 35 and 37). Moreover, the rejected claims optionally require:
the cargo is endogenously secreted by the T3SS (claim 38);
the minicell or the parent bacterial cell has been modified to increase the level of the cargo in the minicell (claim 39);
the cargo is not endogenously secreted by the T3SS (claim 40);
the cargo is endogenously secreted by a T3SS from a species other than the minicell T3SS species, is endogenously secreted by a Type 4 secretion system (T4SS), or is endogenously secreted by a Type 6 secretion system (T6SS) (claim 41);
the cargo has been modified for delivery by the T3SS (claim 43);
the cargo is an enzyme, a DNA-modifying agent, a chromatin-remodeling agent, a gene editing agent, a nuclear targeting agent, a binding agent, an immunogenic agent, or a toxin (claim 44);
the cargo has been modified by addition of a secretion signal (claim 52);
the parent bacterial cell is an E. coli cell (claim 55);
the parent bacterial cell does not comprise an endogenous T3SS (claim 56);
the T3SS is a Salmonella T3SS, a Vibrio T3SS, an Escherichia T3SS, a Yersinia T3SS, a Shigella T3SS, a Pseudomonas T3SS, or a Chlamydia T3SS (claim 57);
wherein the Salmonella T3SS is a Salmonella enterica T3SS, the Vibrio T3SS is a Vibrio parahaemolyticus T3SS, the Escherichia T3SS is an enteropathogenic E. coli (EPEC) T3SS, the Yersinia T3SS, is a Yersinia enterocolitica T3SS, or the Shigella T3SS is a Shigella flexneri T3SS (claim 58);
the parent bacterial cell comprises one or more heterologous nucleotide sequences encoding the components of the T3SS (claim 59);
wherein the one or more nucleotide sequences encoding the components of the T3SS are carried on a vector (claim 60);
the parent bacterial cell has been transiently or stably transformed with the vector (claim 61);
the parent bacterial cell further comprises a moiety that increases the level of the T3SS in the minicell, wherein the moiety is a transcriptional activator of the one or more heterologous nucleotide sequences encoding a component of the T3SS; or
the minicell is derived from a parent bacterial cell that comprises a minCDE mutation and does not comprise an endogenous T3SS, wherein the minicell comprises a bacterial Type 3 secretion system (T3SS) that is heterologous to the parent bacterial cell and further comprises at least one cargo, wherein the T3SS is capable of delivering the cargo to a target cell.
The specification defines the term "achromosomal dynamic system" or "ADAS" refers to a genome-free, non-replicating, enclosed membrane system comprising at least one membrane and having an interior volume suitable for containing a cargo (e.g., one or more of a nucleic acid, a plasmid, a polypeptide, a protein, an enzyme, an amino acid, a small molecule, a gene editing system, a hormone, an immune modulator, a carbohydrate, a lipid, an organic particle, an inorganic particle, or a ribonucleoprotein complex (RNP)). In some embodiments, ADAS are minicells or modified minicells derived from a parent bacterial cell (e.g., a gram-negative or a gram-positive bacterial cell). Furthermore the specification defines the term "endogenous Type3 secretion system" or "endogenous T3SS" as referring to a T3SS that is present on a cell (e.g., a parent cell), or an ADAS derived therefrom, and is naturally encoded by the cell (e.g., is encoded by a wild-type version of the cell). The T3SS may be expressed by the endogenous genes of the cell, and/or may be encoded and expressed by a synthetic construct in the cell. Expression or abundance of an endogenous T3SS may be increased, e.g., by the addition of a moiety that increases the abundance of the T3SS (e.g., a transcriptional activator of the T3SS) or reduction or removal of a negative regulator of expression of the T3SS and the term "heterologous Type3 secretion system" or "heterologous T3SS" as referring to a T3SS that is present on a cell (e.g., a parent cell), or an ADAS derived therefrom, and is not naturally encoded by the cell (e.g., is not encoded by a wild-type version of the cell). The cell may encode another T3SS, or may not encode any T3SS. In some embodiments, the T3SS is expressed by a synthetic construct in the cell (see pages 4 and 5).
To fulfill the written description requirements set forth under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, the specification must describe at least a substantial number of the members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicant has possession the claimed invention. To adequately describe the genus of minicells, Applicant must adequately describe which combination of molecules (i.e. heterologous T3SS, signal sequences, accessory proteins etc.) give rise to an minicells with the claim biological characteristics (e.g. to deliver a given cargo to a target cell). The specification, however, does not disclose distinguishing and identifying features of a representative number of members of the genus of minicells to which the claims are drawn, such as a correlation between the structure of the minicells its recited function (delivering a cargo to a given target cell), so that the skilled artisan could immediately envision, or recognize at least a substantial number of members of the claimed genus of minicells .It should be noted that there are no limitations with regard to the parental strains; the T3SS (or its equivalent) or the cargo that has to be delivered to a target cell nor is there any limitations with regard to any signal sequences that may be employed. Consequently, the instant claims are drawn to an incalculable numbers components that can make up a given minicell. The specification discusses the various types of ADAS (and to a lesser extent minicells) in prophetic terms but is limited with regard to any concrete examples of any minicells with the claimed biological characteristics and functions. Given the specification is silent with regard to what specific combination of components will give rise to an minicell with the recited characteristics, none of these sequences meet the written description provision of 35 USC 112, first paragraph. Moreover, the limited number of examples set forth in the specification is not representative of the claimed genus as the instant claims encompass an incalculable number of minicells. With the exception of the few variants listed in the Examples, the specification is silent with regard to minicells that possess a given biological/immunological activity and that the only way to discern which variants have a claimed biological or immunological activity is empirically. Consequently, given the number and complexity of the minicells encompassed by the instant claims the specification provides insufficient written description to support the genus of minicell variants encompassed by the claim.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed' ”. The courts have decided:
The purpose of the “written description” requirement is broader than to merely explain how to “make and use”; the applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the “written description” inquiry, whatever is now claimed.
See Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). Furthermore, the written description provision of 35 USC § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
MPEP 2163.02 further states, “[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention” See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Additionally, MPEP 2163 states:
"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)”
And:
For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
Given the skilled artisan would not be able to predict whether a given T3SS from a given parental bacterial cell would give rise to an minicell with the claimed biological characteristics as required by the written description requirements proper written description is lacking.
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.
Claims 35, 37-41, 43-44, 52 and 55-63 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Galan et al. (U.S. Patent Application Publication US 2015/0140037 – IDS filed on 3-15-2024) for the reasons set forth in the previous Office action in the rejection of claims 35, 37-41, 43-44, 52 and 55-63.
Applicant argues:
1. Galan does not teach or suggest minicells comprising a heterologous T3SS.
Applicant’s arguments have been fully considered and deemed non-persuasive.
With regard to Point 1, Galan et al. disclose that the parental strain can be a Shigella spp., Yersinia spp., Escherichia coli or a Pseudomonas spp. and that bacterial minicell can comprise the T3SS is encoded by the Salmonella pathogenicity island-1 (see paragraph [0081]). Therefore, contrary to Applicants assertion, Galan et al. does disclose the minicells with a heterologous T3SS.
As outlined previously, Galan et al. disclose bacterial minicells which retain the ability to secrete and deliver a desired compound via the type III secretion system (T3SS). Galan et al. further disclose that said bacterial minicell can be used to deliver a desired antigen (e.g. a polypeptide) to a recipient cell (see paragraph [0030]); that the parental strain can be any a Shigella spp., a Yersinia spp., Escherichia coli, or a Pseudomonas ssp. generally (see paragraph [0081]) or Salmonella enterica specifically (see paragraph [0081]); that the parental bacterial strain is genetically modified so it is non-replicating (see paragraph [0072]) or modified to express a compound of interest to be secreted through the T3SS system (see paragraph [0073]); be modified to overexpress one or more T3SS components (see paragraph [0074]); that the compound of interest to be secreted (i.e. the cargo) can include peptides, proteins, nucleic acids, and small molecules (see paragraph [0084); the use of T3SS targeting signals and secretion signals to modify the “cargo” (see paragraphs [0173] and [0177] for example); and the use of vectors to introduce nucleic acids into the parental bacterial cell or the bacterial minicell (see paragraphs [0093]-[0104]). Finally, Galan et al. disclose that the minicells can contain mutations in the minA, minB, minC and minD genes (see paragraph [0082] for example). Given there are no limitations regarding the structure of the T3SS and components thereof of the instant claims (i.e. minicells), Galan et al. anticipates all the limitations of the rejected claims.
New Grounds of Rejection
35 USC § 112
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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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 59-61 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, 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 independent claim already requires that the T3SS be heterologous to the parent cell. 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.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ROBERT A ZEMAN/Primary Examiner, Art Unit 1645 April 3, 2026