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 .
Election/Restrictions
Applicants’ election without traverse of Group I (i.e., Claims 1-4 and 8, drawn to a recombinant bacterial Contractile Injection System (CIS) or a Metamorphosis Associated Contractile Structure (MAC)) in the reply filed on September 4th 2024 is acknowledged. Additionally, Applicants’ election without traverse of Species A (i.e., A single and specific proteinaceous cargo, i.e., Mif1 protein or a fusion protein comprising the Mif1 protein, (please see claims 1 and 5), and if a fusion protein, then a single and specific fusion protein (please see claims 1 and 5-6), and including indication of the following: (1) a single and specific sequence identification number for Mif1 protein (please see claims 1 and 5); Applicants’ Election: SEQ ID NO: 2; (2) a single and specific structure containing the proteinaceous cargo, i.e., a CIS or MACs (please see claims 1-6, 9), Applicants’ Election: a Mif1 protein having the amino acid sequence SEQ ID NO: 2; (3) a single and specific expression system of the CIS or MACs, if necessary, i.e., liposome/lipid-containing nanoparticle, protoplast/spheroplast, or a cell (please see claims 1-5, 9), Applicants’ Election: liposome; AND (4) if a cell is elected as the expression system, then a single and specific cell, i.e., microbial or eukaryotic (please see claims 4-5, 7-9, 12-13)), in the reply filed on September 4th 2024 are acknowledged.
It is noted that Applicants did not specify whether the proteinaceous cargo is a Mif1 protein or a fusion protein comprising Mif1. However, since Applicants’ election for a proteinaceous cargo is an active biological agent. Applicants’ election is being interpreted as that the proteinaceous cargo is a fusion or a recombinant protein comprising a Mif1 (see Claims 1, 5 and 20-21).
Claims 3-4, 8, and 19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 September 4th 2024.
Status of Claims
Claims 1-11 were originally filed an amended on May 17th 2021. The amendment amended claims 1-5 and 7-9, cancelled claims 10-11, and added new claims 12-13.
The amendment filed on September 4th 2024, amended claims 1-4 and 8; cancelled claims 5-7, 9-13 and added new claims 14-28.
The amendment filed on January 29th 2025, amended claims 1-2, 8, 17-18, 20-25; canceled claims 14-16; and added new claims 29-36.
The amendment filed on January 14th 2026, amended claims 1-2, cancelled claims 3, 4, 8 and 19; and added new claims 37-39.
The amendment filed on June 8th 2026, amended claims 1-2, 17, 20, 22-24, 29-33 and 35-36.
Priority
The present application claims status as a 371 (National Stage) of PCT/US19/61839 filed November 15th 2019, and claims the benefit under 35 U.S.C 119 (e) to U.S. Provisional Application No. 62/844,988 filed May 8th 2019 and to U.S. Provisional Application No. 62/768,240 filed November 16th 2018. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C 119 (e) or under 35 U.S.C 120, 121, or 365 (c) is acknowledged.
Sequence Interpretation
Regarding claims 1-2, please note that the Examiner is interpreting the scope of the Mif1 protein as requiring about 100% sequence identity to SEQ ID NO: 2, with any N-/C-terminal additions. As stated in the instant spec, the term “about” can be understood as within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1% of the stated value (see instant specification, pg. 28, lines 30-31).
Claim Interpretation
For purposes of applying prior art, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation set forth below, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
For claims 1-2, 17, 20, 22-24, 29-33 and 35-36, regarding the scope of “Contractile Injection System (CIS) or Metamorphosis Associated Contractile Structure (MACs)”, it is noted that the instant specification does not define what constitutes “Contractile Injection System (CIS) or Metamorphosis Associated Contractile Structure (MACs)”. Rather, the instant specification recites syringe-like structures called Contractile Injection Systems (CIS) are specialized to puncture membranes and often deliver effectors to target-cells (see instant specification, pg. 2, lines 6-7 and lines 9-10). A CIS mediating beneficial relationship between gram-negative bacterium Pseudoalteramonas luteoviolacea and marine tubeworm Hydroides elegans was characterized and named “Metamorphosis Associated Contractile structure” (MACs), because it stimulates metamorphosis of Hydroides (see instant specification, pg. 2, lines 13-16).
Pursuant to MPEP 2111.01, under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art before the effective filing date of the claimed invention. Brackmann et al. define contractile nanomachines as effective and powerful systems for physically piercing membranes and allowing the translocation of macromolecules such as DNA or proteins (see Brackmann et al., Trends in Cell Biology, 2017, Vol. 27, No. 9, pp. 623-632, at pg. 623, first paragraph). Brackmann et al. describe the basic mechanism of membrane puncturing by contractile nanomachines with a focus on the bacterial Type VI Secretion System (T6SS) (see Brackmann, pg. 623, abstract). Brackmann et al. add that all contractile nanomachines comprise three major parts: a baseplate, a long tube with a sharp tip, and a contractile helical sheath that wraps around the tube and attaches to the baseplate (see Brackmann et al., pg. 623, first paragraph). Therefore, the Examiner is interpreting the scope of a Contractile Injection System (CIS) as a multi-part structure consisting of a baseplate, a tube with a sharp tip, and a contractile helical sheath. The Examiner is also interpreting Metamorphosis Associated Contractile Structure (MACs) as specific sub-type or specialized class of CIS.
Response to Amendment
The Declaration under 37 CFR 1.132 filed 06/08/2026 is insufficient to overcome the rejection of claims 1-2, 17-18, 20-29 based upon the 35 U.S.C 112(a) rejection (i.e., enablement requirement) as set forth in the last Office action.
Declarant’s arguments pertaining to the distinction between CIS and MAC structures are appreciated. However, these arguments, in addition to arguments pertaining to the encapsulation of biological cargo within liposome-based systems are not sufficient to overcome the enablement requirement, because independent claims 1 and 2 have been amended to exclude the CIS or MAC contractile structures. Therefore, Declarant’s arguments support the lack of enablement requirement because the amended claims contain subject matter which was not described in the specification.
In particular, Declarant acknowledges “that encapsulation of bacteriophages within liposomes provides a particularly strong and directly relevant precedent for the encapsulation of contractile injection systems (CIS) and MACs, as bacteriophages share structural, compositional, and physical features with CIS and MACs, including proteinaceous composition, high surface charge, and the presence of elongated tail structures; and that multiple studies have demonstrated that intact bacteriophage particles, including both short- tailed podoviruses and long-tailed myoviruses, can be successfully encapsulated within lipid vesicles using a variety methods known at the time of this invention” (see Declaration, filed 06/08/2026, pg. 6, point 13).
Therefore Declarant’s arguments are being interpreted as that the CIS or MAC structures including proteinaceous compositions (e.g., proteinaceous cargo or heterologous protein linked to Mif1 protein represented by SEQ ID NO: 2) can be encapsulated within a liposome. Thus it is apparent that the Metamorphosis-Inducing Factor 1 Mif1 protein requires a specialized class of contractile structure, such as a Metamorphosis-Associated Contractile structure (MAC). Although liposome encapsulation of bacteriophages and/or proteinaceous cargo was known at the time of the instant invention; the instant specification is silent about a liposome having encapsulated therein a proteinaceous cargo or heterologous peptide linked to Mif1 protein represented by SEQ ID NO: 2, and it is also silent about a liposome having encapsulated therein a proteinaceous cargo or heterologous peptide linked to Mif1 protein represented by SEQ ID NO: 2 in the absence of a specialized contractile structure (i.e., MACs).
Contrary to Declarant’s arguments, the instant specification does not enable any person skilled in the art to which it pertains to make and/or use the invention commensurate in scope with the claims. The state of the prior art is highly relevant with regard to liposome encapsulation of contractile structures and their respective proteinaceous cargo; however one skilled in the art cannot readily anticipate the effect of liposome encapsulation of an effector protein (i.e., Mif1 protein) without its specialized contractile structure, because there is lack of predictability in the art.
Accordingly, the 35 U.S.C 112(a) rejection of claims 1-2, 17-18, 20-39 has been maintained.
Response to Arguments
1. Applicants’ arguments, see Remarks, filed 06/08/2026, with respect to 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement, have been fully considered but are not persuasive. The 35 U.S.C. 112(a) rejection to claims 1-2, 17-18, 20-36 has been maintained.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
1. Claims 1-2, 17-18, 20-39 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. This is a new matter rejection.
Claims 1 and 2 are drawn to a liposome or lipid-comprising nanoparticle comprising and having encapsulated therein a proteinaceous cargo or a heterologous protein or peptide; wherein the proteinaceous cargo or the heterologous protein or peptide consists of, or is linked to a Metamorphosis-Inducing Factor 1 Mif1 protein comprising a sequence having about 100% sequence identity to SEQ ID NO: 1. Thus, the scope of the claims encompass proteinaceous cargo comprising a Mif1 protein having about 100% sequence identity to SEQ ID NO: 2 encapsulated within a liposome or lipid-comprising nanoparticle. The claims have been amended to omit recombinant Contractile Injection Systems (CIS) or a Metamorphosis-Associated Contractile structure (MACs), thereby resulting in a broader, more generic invention.
Applicants stated in their remarks that “no previously presented matter is introduced by the instant Amendment” (see Remarks, filed 06/08/2026, pg. 1). However, the support (i.e., the specification and/or the claims as originally filed) do not support that the subject matter of amended claims 1 and 2 was previously presented as the there is no mention of whether a Metamorphosis-Inducing Factor 1 Mif1 protein having about 100% sequence identity to SEQ ID NO: 2 can be encapsulated within a liposome.
Pursuant to MPEP 2163.05(I) A, a claim that omits an element which applicant describes as an essential or critical feature of the invention originally disclosed does not comply with the written description requirement.
The specification is void of evidence that would clearly support the omission of CIS or MACs. The specification does not teach the specifically claimed liposome being free of a CIS or MACs. Examination of the instant support shows that the envisioned Mif1 protein (i.e., JF50_12615 named Mif1, see spec pg. 57, lines 5-7) is sufficient to stimulate metamorphosis when delivered by electroporation (see instant specification, pg. 48, lines 14-16). However, JF50_12615 (i.e., Mif1) is unable to induce metamorphosis when added exogenously (see instant spec, pg. 48, lines 4-6 and pg. 49, lines 9-13 and Fig. 14). Thus it is understood that Mif1 requires a delivery mechanism which encompasses puncturing the recipient membrane (e.g., via contractile injection system or electroporation), instead of a less aggressive approach such as membrane fusion (e.g., cargo delivery by liposome or lipid-comprising nanoparticle).
As such, a Metamorphosis Associated Contractile structure (MACs) or a Contractile Injection System (CIS) appears to be an essential element of the claimed proteinaceous cargo encapsulated within the liposome. The instant specification fails to describe the more generic invention as recited in the instant claims. Therefore, the instantly claimed genus of liposome being free CIS or MAC is not expressly described nor has it been adequately supported.
Modified/Maintained Rejections in light of Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
2. Claims 1-2, 17-18 and 20-39 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 enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, "The Federal Circuit has repeatedly held that "the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation'." In re Wriqht, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)" (emphasis added). The "make and use the full scope of the invention without undue experimentation" language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: "A lack of enablement for the full scope of a claim, however, is a legitimate rejection. "The principle was explicitly affirmed most recently in Auto. Tech. Int'l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortriqht, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
As stated in MPEP §2164.01(a), “there are many factors to consider when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any experimentation is ‘undue’.” These factors include, but are not limited to:
1.The breadth of the claims;
2.The nature of the invention;
3.The state of the prior art;
4.The level of skill in the art;
5.The level of predictability in the art;
6.The amount of direction provided by the inventor;
7.The presence or absence of working examples;
8.The quantity of experimentation needed to make or use the invention based on
the disclosure.
See In re Wands USPQ 2d 1400 (CAFC 1988).
The eight In re Wands factors are applied to claims 1-2, 17-18 and 20-39 as follows:
Breadth of the Claims and the Nature of the Invention
Claims 1-2, 17-18 and 20-39 are drawn to “a liposome or lipid-comprising nanoparticle comprising and having encapsulated therein a proteinaceous cargo or a heterologous protein or peptide…” as recited in instant claim 1; or “a liposome or lipid-comprising nanoparticle having encapsulated therein a proteinaceous cargo or a heterologous protein or peptide” as recited in instant claim 2. The Applicants claim a liposome or lipid-comprising nanoparticle having encapsulated therein a proteinaceous cargo or homologous protein or peptide is linked to a Metamorphosis-Inducing Factor 1 Mif1. Details disclosed in the specification do not show a liposome or lipid-comprising nanoparticle having encapsulated therein a proteinaceous cargo or heterologous peptide linked to or consisting of Metamorphosis-Inducing Factor 1Mif1 protein.
Instead, the specification discloses:
Example 1, which shows evidence that MACs from P. luteoviolacea is effective on eukaryotic cells (i.e., kills insect cell lines in vitro) (see instant specification, pg. 30 to pg. 31), and evidences the identification of a MAC toxic effector, i.e., gene JF50_12610, and an extracellular CIS (eCIS) effector, i.e., Pne1, required to kill insect cell lines, yet does not stimulate metamorphosis of the tubeworm Hydroides (see instant specification, pg. 31 to 40).
Example 2, which shows evidence of the Metamorphosis-Inducing Factor 1, i.e., gene JF50_12615, responsible for the metamorphosis of tubeworm Hydroides; as well as the function of the contractile injection systems (MAC or CIS or eCIS) required deliver the metamorphosis inducing cargo (see instant specification, pg. 43 to pg. 57); and
Example 3, which teaches distinct contractile injection systems found in a majority of adult human microbiomes (see instant specification, pg. 58-66).
However, Applicants failed to provide evidence in the specification that a proteinaceous cargo or a heterologous protein or peptide linked to or consisting of a Metamorphosis-Inducing Factor 1 Mif1 protein can be encapsulated by a liposome or lipid-comprising nanoparticle in particular wherein the Mif1 protein comprises a sequence having at least about 100% sequence identity to SEQ ID NO: 2.
Accordingly, claims 1-2, 17-18 and 20-39 are unduly broad with respect to a liposome or lipid-comprising nanoparticle comprising and having encapsulated therein a recombinant CIS or a MACs; and with respect to a liposome or lipid-comprising nanoparticle having encapsulated therein a Mif1 protein comprising a sequence having at least about 100% sequence identity to SEQ ID NO: 2.
The State of the Prior Art
Although the state of the art is relatively high with regard to the expression of recombinant proteins, the state of the art with regard to a Mif1 encapsulated by a liposome or lipid-comprising nanoparticle is undeveloped. In particular, encapsulating proteinaceous cargo comprising an effector protein (i.e., Mif1) without its respective contractile injection system (eCIS or MACs) in a liposome or a lipid-comprising nanoparticle is not the standard for encapsulating proteinaceous cargo. Therefore, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which the claimed invention pertains (i.e., liposome or lipid-comprising nanoparticle and encapsulation of a proteinaceous cargo, or a heterologous protein or peptide wherein the proteinaceous cargo comprises Mif1 protein having about 100% sequence identity to SEQ ID NO: 2), then there is a lack of predictability in the art. Moreover, it is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity.
The court has indicated that the more unpredictable an area is the more specific enablement is necessary in order to satisfy the statute. (See In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970)). This is because it is not obvious from the disclosure of one species, what other species will work. As such, a liposome or lipid-comprising nanoparticle comprising and having encapsulated therein a proteinaceous cargo comprising Mif1 having about 100% sequence identity to SEQ ID NO: 2 without its contractile injection system (i.e., eCIS or a MACs) involves a very high level of unpredictability.
The Level of Skill in the Art
Practitioners in this art (scientist, researchers, biochemists and/or pharmaceutical chemists) would presumably be highly skilled in the art of liposome or lipid-comprising nanoparticles and encapsulating therein a proteinaceous cargo.
The Level of Predictability in the Art
The court has indicated that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. (See In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970)). In the instant case, Applicants do not demonstrate a liposome or lipid-comprising nanoparticle comprising and having encapsulated therein a proteinaceous cargo comprising Mif1. Rather, Applicants only demonstrate the function and origin of JF50_12615, which was named Mif1 for Metamorphosis-Inducing Factor 1 (see instant specification, pg. 57, lines 6-7), the presence of the proteinaceous effector within the rigid inner tube lumen of a CIS or MAC (see instant specification, pg. 43, lines 14-15), and the in vitro effect of other P. luteoviolacea effectors on insect cells (see instant specification, Example 1, pgs. 30-31 and 33).
Applicants appear to rely on the assumption that by providing in vitro evidence that Mif1 kills insect sects when delivered via electroporation, and based on liposome embodiments (i.e., prophetic examples), that the claimed invention would not require undue experimentation. However, such an assumption cannot be made because there is no indication in the prior art of encapsulation of proteinaceous cargo comprising an effector such as Mif1 without its respective injection system (i.e., CIS or MACs) by a liposome or lipid-comprising nanoparticle.
Additionally, since the specification fails to demonstrate any data or evidence or working examples of the claimed liposome or lipid-comprising nanoparticle, there would be no way of determining without undue experimentation whether the instantly claimed liposome or lipid-comprising nanoparticle comprising the effector protein Mif1 without its respective injection system would exhibits the desired result of metamorphosis inducing factor. Without more experimentation demonstrating the efficacy of the claimed liposome or lipid-comprising nanoparticle, the level of unpredictability remains high. Therefore, it is unpredictable that the claimed liposome or lipid-comprising nanoparticle would function as intended.
The Amount of Direction Provided by the Inventor and The Presence or Absence of
Working Examples
The specification does not enable any person skilled in the art to which it pertains to make and/or use the invention commensurate in scope with the claims. There is a lack of adequate guidance from the specification or prior art with regard to the actual liposome or lipid-comprising nanoparticle comprising and having encapsulated therein a Mif1 protein without its injection system (i.e., CIS or MAC). Applicants fail to provide the guidance and information required to ascertain whether the claimed liposome comprising the effector protein Mif1 would exhibit the desired function without resorting to undue experimentation.
Absent a reasonable a priori expectation of success for encapsulating a Mif1 in the absence of the contractile injection system (CIS or MACs), one skilled in the art would have to extensively test the efficacy of the claimed invention in vitro and in vivo. Since each prospective embodiment, and indeed future embodiments as the art progresses, would have to be empirically tested, and those which initially failed tested further, an undue amount of experimentation would be required to practice the invention as it is claimed in its current scope because the specification provides inadequate guidance to do so otherwise.
The amount of direction or guidance presented in the specification is limited. The specification is silent regarding any working examples where a proteinaceous cargo comprising Mif1 in the absence of its contractile system (CIS or MAC) is encapsulated by a liposome or lipid-comprising nanoparticle. Therefore, a person of ordinary skill in the art would reasonably require an undue quantity of experimentation.
The Quantity of Experimentation Needed
In light of the unpredictability surrounding the claimed subject matter, the breadth of the claimed invention, and the lack of adequate guidance, one wishing to practice the presently claimed invention would be unable to do so without engaging in undue experimentation. To practice the presently claimed invention, one would have to gather additional data and perform experimentation to determine whether the claimed liposome or lipid-comprising nanoparticle exhibits the desire effect and/or function. Additional experimentation may include, but is not limited to, performing benchwork and additional analysis in in vitro/in vivo, in animal models as well as performing clinical trials in subjects.
Conclusion of 35 U.S.C. 112(a) (Enablement) Analysis
MPEP §2164.01(a), 4th paragraph, provides that, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, before the effective filing date of the claimed invention, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC), states that, “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable,” citing Brenner v. Manson, 383 U.S. 519, 536 (1966) (stating, in the context of the utility requirement, that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion”). The Genentech decision continued, “tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Id. at p. 1005.
After applying the Wands factors and analysis to claims 1-2, 17-18 and 20-39, in view of the Applicants’ entire disclosure, and considering the In re Wright, In re Fisher and Genentech decisions discussed above; it is concluded that the practice of the invention as claimed in claims 1-2, 17-18 and 20-39, would not be enabled by the written disclosure. Therefore, claims 1-2, 17-18 and 20-39, are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skilled in the art to encapsulate a proteinaceous cargo comprising Mif1 in the absence of its contractile injection system in a liposome or lipid-comprising nanoparticle.
Accordingly, the 35 U.S.C 112(a) rejection to claims 1-2, 17-18, 20-39 has been maintained.
Response to Arguments
Applicants' arguments filed on 06/08/2026, with respect to 35 U.S.C. 112(a) rejection have been fully considered but they are not persuasive.
The instant amendment does not cure the lack of evidence with regard to a liposome or lipid-comprising nanoparticle comprising and having encapsulated therein a proteinaceous cargo or a heterologous protein or peptide, wherein the proteinaceous cargo, or the heterologous protein or peptide consists of: (a) the proteinaceous cargo or the heterologous protein or peptide linked to (b) a Metamorphosis-Inducing Factor 1 Mif1 protein, as recited in instant claim 1.
The instant amendments do not compensate for the lack of evidence with regard to a liposome or lipid-comprising nanoparticle having encapsulated therein a proteinaceous cargo, or heterologous protein or peptide linked to a Metamorphosis-Inducing Factor 1 Mif1 protein, as recited in instant claim 2.
As previously discussed in the 35 U.S.C. 112(a) rejection above, the specification does not enable any person skilled in the art to which it pertains to make and/or use the invention commensurate in scope with the claims. There is a lack of adequate guidance from the specification and prior art with regard to the instantly claimed liposome.
MPEP 2164.03 states that [t]he amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The "amount of guidance or direction" refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004).
Since the art pertaining to the encapsulation of a proteinaceous cargo comprising Mif1 protein by liposomes or lipid-comprising nanoparticles is undeveloped; and since encapsulation a proteinaceous cargo comprising the effector Mif1 protein in the absence of its injection system (i.e., CIS or MACs) by liposomes or lipid-comprising nanoparticles is unpredictable; a higher level of disclosure is required to allow a person of ordinary skill in the art to practice the "full scope" of the claimed invention without undue experimentation.
The instant specification lacks working examples of a liposome or lipid-comprising nanoparticle comprising and having encapsulated therein the claimed Mif1 protein in the absence of its CIS or MACs. The instant specification only provides embodiments (i.e., prophetical examples) of liposomes comprising the claimed CIS or MACs and its effector protein (i.e., JF50_12615 named Mif1) and working examples (i.e., Examples 1-3) of the recombinant bacterial CIS or MACs. Therefore, Applicants fail to provide the guidance and information required to combine the liposome or lipid-comprising nanoparticle and the claimed proteinaceous cargo comprising Mif1 in the absence of CIS or MACs. Thus, an ordinary skilled artisan would not be able to make and/or use the claimed invention without resorting to undue experimentation.
Examiners’ Comment
The closest prior art is WO 2013/126622 with International Publication Date of August 29th 2013 (cited in the IDS filed on 06/08/2021)(herein after “Mekalanos”), and WO 2018/129536 A1 with International Publication Date of July 12th 2018 (herein after “Rohwer”).
Mekalanos teaches expression of VipA and VipB polypeptides which refer to intracellular tubular proteins that form an intracellular tubular structure, VipA and VipB polypeptides are involved in the Type VI secretion system (i.e., T6SS) in prokaryotes and can be derived from bacterial species (see Mekalanos, pg. 12, para[00076-00077] and pg. 16, para[00094]). Mekalanos also teaches displaying a polypeptide on a tubular structure, meaning that the protein of interest is tethered or fused to the external surface of the tubular structure and is thus displayed or presented to the environment surrounding the tubular structure (see Mekalanos, pg. 10, para[00067]). The fusion protein is expressed in a bacterial strain from which the first and second intracellular tubular proteins are derived; the bacterial culture is grown under conditions in which the Type VI secretion system (T6SS) is functionally expressed (see Mekalanos, pg. 22, para[000110]). However, Mekalanos does not teach or suggest a Metamorphosis Inducing Factor 1 protein, nor wherein the Mif1 comprises a sequence having about 100% sequence identity to instant SEQ ID NO: 2.
Rohwer teaches delivering (iv) a Metamorphosis Associated Contractile Structure (MACs), into the blood stream or lymphatic system of an animal, e.g., a mammal, or delivering (iv) to a tissue organ of the animal in vivo; and/or delivering a payload, e.g., a drug, an effector nucleic acid, an immunogen, a label (see Rohwer, pg. 1, lines 14-33 to pg. 2, lines1-10). Rohwer also teaches that the payload comprises a composition heterologous to (iv) the Metamorphosis Associated Contractile structure (MACs) (see Rohwer, pg. 74, lines 1-6); and that the payload or composition comprises a synthetic nucleic acid or a recombinantly engineered nucleic acid, a protein or a peptide, a lipid, an antibody or a small molecule (see Rohwer, pg. 76, lines 8-34). Rohwer adds that a liposome, a nanostructure or a nanoparticle capable of targeting a specific cell, tissue or organ in vivo, or a microbe or bacteria, where the specific targeting is effected by incorporation of a component of (iv) a Metamorphosis Associated Contractile structure (MACs) (see Rohwer, pg. 26, lines 6-19). However, Rohwer does not teach or suggest a Metamorphosis Inducing Factor 1 protein, nor wherein the Mif1 comprises a sequence having about 100% sequence identity to instant SEQ ID NO: 2.
Conclusion
No claims are 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).
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/CLAUDIA ESPINOSA/Patent Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
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