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 .
This action is Non-Final.
Status of the Claims
Claims 16, 18-28, and 33 are currently pending.
Claims 26, 27 and 28 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species and Invention, there being no allowable generic or linking claim.
Claims 1-15, 17, and 29-32 are cancelled.
Claims 16, 18-25, and 33 have been considered on the merits.
Withdrawn Rejections
The 35 U.S.C. 103 rejections made onto the claims have been withdrawn in light of the Remarks and Declaration submitted on 07/06/2026.
New Rejections
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.
Claims 16, 18-25, and 33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
An in vitro method for obtaining B cells modified to express a heterologous gene of interest, comprising a step of infecting B cells with a stable lentiviral particles pseudotyped with an endogenous retroviral syncytin (ERV syncytin) in the presence of an LAH4-A4 DNA transfection agent and packaging a heterologous gene of interest, which have a high physical and/or infectious titer(s)
wherein the concentration of the stable lentiviral particles pseudotyped with the ERV syncytin is at least 106 TU/ml.
However, the specification does not reasonably provide enablement for claim 16 as currently presented. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(a)). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case are discussed below.
(1) The nature of the invention
The specification describes the invention as a method of obtaining B cells modified to express a heterologous gene of interest. Also provided are compositions of stable pseudotyped lentiviral particles and uses thereof.
(2) the breadth of the claims
Independent claim 16 broadly encompasses a method of obtaining B cells modified to express a heterologous gene of interest through the single step of infecting B cells with stable lentiviral particles pseudotypes with an ERV syncytin. Dependent claims 24 and 25 limit wherein the method is performed in the presence of a LAH4 peptide selected from the claimed SEQ ID NOs. However, the claims do not limit the concentration of the stable lentiviral particles at any point. Thus, the claims taken together with the specification imply that the method is able to obtain B cells modified to express a heterologous gene of interest through the step of contacting the B cells with the stable lentiviral particles pseudotyped with ERV syncytin at any concentration of the lentiviral particles, and that the presence of the LAH4 peptide is optional for the successful completion of the method, which is unpredictable.
(3) The state of the prior art
The prior art shows transfecting B cells with a heterologous gene of interest to be difficult to achieve and unpredictable.
(4) the predictability or unpredictability of the art:
The claims embody a method of obtaining B cells modified to express a heterogenous gene of interest, comprising the single step of infecting B cells with stable lentiviral particles pseudotyped with an ERV syncytin at any concentration of lentiviral particles and without also infecting the B cells with the lentiviral particles in the presence of a LAH4 peptide, which is unpredictable.
The method is found to be unpredictable with regards to the ability of the method to successfully obtain B cells modified to express a heterologous gene of interest using any concentration of stable lentiviral particles and without also infecting the B cells with the lentiviral particles in the presence of a LAH4 peptide, which is unpredictable based on the instant specification.
Regarding the concentration of the stable lentiviral particles, the instant specification states that “the B cell transducing effects of LV-syna and LV-Syn2 were found to be vector concentration dependent (Figure 4) and transgene independent. Almost all peripheral blood CD19+ cells could be transduced using 106 TU/mL of LV-syn1 or LV-syn2 vectors” (pg. 39, para 1). Additionally, Figure 4 demonstrates that at 106 TU/mL both LV-Syn1 and LV-Syn2 have transduction efficiencies between 92-98%. Therefore, the instant specification demonstrates that to effectively transduce B cells a concentration of at least 106 TU/mL is required in the method.
Regarding completing the method in the presence of an LAH4 peptide, the instant specification provides Table 3 on pg. 40 of the specification. Table 3 demonstrates that in all B cell subsets tested less than 5% of cells are transduced with LV-Syn1 or LV-Syn2 when Vectofusin®-1 is not present during transfection. Vectofusin®-1 is a trademarked and refers to a LAH4-A4 peptide which acts as a DNA transfection agent. When Vectofusin®-1 is present during the infecting B cells with the stable lentiviral particles of the instant claims, the percent of cells transduced ranges from about 20-60%, with the highest population of B cells transduced being Naïve B cells (pg. 40, Specification).
Therefore, this method is found to be unpredictable with regards to the method’s ability to successfully transduce B cells at any concentration of lentiviral particles and without the method being conducted in the presence of a LAH4-A4 peptide.
(5) The relative skill of those in the art:
The relative skill of those in the art is high.
(6) The amount of direction or guidance presented
The specification details examples 1-3. Example 1 details the transduction of human primary B cells and dendritic cells. Example 2 details in vivo gene delivery in mice. Example 3 details determining physical titers.
(7) the presence or absence of working examples:
With specific regards to working examples, the specification teaches Example 1 which details the transduction of many subsets of B cells at working concentrations of the lentiviral particles and in combination with Vectofusin®-1. This example encompasses a working model of an embodiment of independent claim 16.
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed above and the high unpredictability and the lack of
guidance provided in the specification, one of ordinary skill in the art would be burdened with undue
experimentation to use the claimed invention within the broad scope as instantly claimed.
It is the examiner’s position that one skilled in the art could not practice the invention
commensurate in the breadth of the claims without undue experimentation. Therefore, claim 16
and its dependents are rejected under 35 U.S.C. 112, first paragraph, for a lack of scope of enablement.
Response to Arguments
Applicant’s arguments, see Remarks, filed 07/06/2026, with respect to the rejection(s) of the claims under 35 U.S.C. 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made above under 35 U.S.C. 112(a).
Declaration Under 37 C.F.R. § 1.132 of Anne Galy
The Declaration submitted under 37 C.F.R. § 1.132 by Anne Galy has been considered and is found persuasive, thus the related art rejections have been withdrawn. However, as described in the “Response to Arguments” section, a new ground(s) of rejection is made above under 35 U.S.C. 112(a).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632
