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
Applicant’s election without traverse of Group I and the following species: intradermal injection; covalent conjugation; receptor binding molecules; Mycobacterium tuberculosis – MHC Class I or II; and Mycobaterium antigen – Mtb secretory antigenic target ESAT6, in the reply filed on 5 January 2026 is acknowledged. Applicant indicates Claims 1-17 and 20-21 read upon the elected species.
Claims 18-19 and 22-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
Claims 1-17 and 20-21 are examined on the merits.
Priority
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, 365(c), or 386(c) is acknowledged. This application claims the benefit of U.S. Provisional Patent Application Serial No. 62/968,648 filed on January 31, 2020; U.S. Provisional Patent Application Serial No. 63/040,340 filed on June 17, 2020; U.S. Provisional Patent Application Serial No. 63/122,307 filed on December 7, 2020; U.S. Provisional Patent Application Serial No. 63/135,699 filed on January 10, 2021; and International Patent Application No. PCT/US2021/025279, filed March 31, 2021.
Claims 1-17 and 20-21 have an earliest effective US filing date of January 31, 2020.
Claim Objections
Claims 1, 20 and 21 are objected to for improper punctuation: See MPEP section 608.01(m), “Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995)”. Specifically, these claims say “Fc.epsilon.R1” and the extra periods need to be removed. Appropriate correction is required.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The following title is suggested: Methods for Detection of Analytes of Mycobacterium Tuberculosis.
Claim Rejections - 35 USC § 112
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.
Claims 1-17 and 20-21 are 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 1 is indefinite wherein it recites contacting “to elicit a multivalent binding response”, which is an intended result/effect that does not impose any structural, material, or manipulative difference on the scope of the claim. The claim is further indefinite wherein it recites “performing an assessment of said multivalent binding response,” without setting forth definite method steps for assessing. Absent clear method steps for performing the assessment, it is unclear what is or is not included in the scope of the claim. It is unclear what processes would infringe the invention or not. This affects the scope of all depending claims. MPEP 2173.05(g) states: “the use of functional language in a claim may fail ‘to provide a clear-cut indication of the scope of the subject matter embraced by the claim’ and thus be indefinite.” It further states: “Examiners should consider the following factors when examining claims that contain functional language to determine whether the language is ambiguous: (1) whether there is a clear cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim” (emphasis added). Since the claims fail to meet all (3) criteria set forth in MPEP 2173.05(g), then Claims 1-17 and 20-21 are rejected.
Claim 3 is similarly indefinite wherein it recites delivering into tissue wherein the contacting, “is exposed to from about 125 to 20,000 mast cells per cubic millimeter.” This is an intended effect since there are no positive, active method steps for assessing cell counts within the tissue.
Claims 8-9 and 12-13 are indefinite because they recite “using” without setting forth the actual method steps for using. MPEP 2173.05(q) states: “Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: "[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon" was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986). Claims 8-9 and 12-13 are analogous to the claims in Erlich since they recite using a device (claim 8) using a sensor (claim 9), using a technique (claim 12) and using a member (claim 13) without any active, positive steps delimiting how this use is actually practiced. Although a claim should be interpreted in light of the specification disclosure, it is generally considered improper to read limitations contained in the specification into the claims. See In re Prater, 415 F.2d 1393, 162 USPQ 541 (CCPA 1969) and In re Winkhaus, 527 F.2d 637, 188 USPQ 129 (CCPA 1975), which discuss the premise that one cannot rely on the specification to impart limitations to the claim that are not recited in the claim.”
Claims 12 and 13 recite the limitation "said constructing step" in Claim 1. There is insufficient antecedent basis for this limitation in the claim. Claim 1 recites “providing”, “contacting” and “performing”. While Claim 1 recites a resulting “construct” (noun) it is unclear if “constructing”, as a verb, pertains to the binding or contacting steps.
Claim 13 is further indefinite under 35 U.S.C. 112(b) wherein it recites, “fashioning” an additional moiety selected from the list of the claims and Applicant has elected receptor binding molecules. Without recitation of method steps, it is unclear what processes are encompassed by and would infringe fashioning receptor binding molecules. Paragraph [0069] of the disclosure states: “For purposes of the present disclosure, the term ‘fashioning’ or ‘fashioned’ is intended to mean the preparation of the analyte binding moiety for incorporation into the reagent construct of the present invention and includes but is not limited to the removal of any extraneous materials unnecessary for incorporating the binding moiety into the reagent construct or for binding to the analyte of interest in order to leave intact the desired analyte binding specificity of the moiety.” When read in light of the specification, it is still unclear what preparation steps fall within the scope of fashioning receptor binding molecules.
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 7-11 and 14 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 claim(s) contains 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.
The factors to be considered in determining whether a disclosure would require undue experimentation include:
A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
The breadth of the claims.
Claim 7 recites evaluating a morphological change in a target tissue; Claim 8 recites using a device to measure a morphological change; Claim 9 recites using a sensor for evaluating a target tissue to render assessment of a multivalent binding response; Claim 10 recites performing a visual inspection for a wheal and flare reaction; and claim 11 recites using a device that measures wheal and flare; Claim 14 recites performing an assessment comprising measuring a substance released during mast cell degranulation.
The amount of direction provided by the inventor and the existence of working examples.
There is no guidance or direction that demonstrates assessing morphological changes in any target tissue within the disclosure as filed, nor is there enabling guidance for any device that measures said morphological changes within a mammalian tissue. Additionally, there is no guidance or direction for a sensor that evaluates a multivalent binding response in tissue in vivo. Lastly, there is no guidance as to how visual inspection for a wheal and flare can be assessed for any tissue in vivo. For example, one of the tissues that Mycobacterium tuberculosis bacteria enter is the spleen and there is no guidance for visually assessing wheal and flare in the spleen. Nor is there enabling support for any device that is capable of performing this. Lastly, while the specification teaches mast cell degranulation comprises the release of granules (paragraph [0046]), the disclosure fails to provide guidance as to when and where mast cells undergo degranulation, and fails to describe what specific substances are released during this process such that one of ordinary skill in the art would be able to measure these substances with a reasonable expectation of success.
Nature of the invention and the level of one of ordinary skill in the art.
Given that the nature of the invention is directed to contacting endogenous mast cells in situ, which reads upon administering to mast cells within tissues in vivo, then the relative level of skill in the art is high. One would have to have ordinary skill in administering compounds in vivo to mammals.
The state of the prior art.
Absent specific enabling guidance for these methods in the disclosure as filed, a person having ordinary skill in the art would have to rely upon what was known in the art regarding each of these claims. While morphological changes in tissues can be assessed by imaging in instances of, for example, tumor growth within a tissue by MRI, the current method is directed to detecting any analyte within tissue in vivo and there is no guidance for assessing changes in analyte that equate to changes in morphology within the tissues. Therefore, the claims are not enabled commensurate in scope with their breadth. Nor is it clear what device or sensor can be used in these methods with a reasonable expectation of successfully detecting changes in mammalian tissue in situ.
Absent explicit guidance within the disclosure as filed, or within the art at the time of filing, a person having ordinary skill in the art would have to perform further experimentation in order to make and use the devices/sensors of the claims and discover how to assess morphological changes, and/or wheal and flare in tissues within the mammal. The amount of experimentation required in order to make and/or use the invention with a reasonable expectation of success, goes beyond what is considered routine in the art and constitutes undue experimentation. This undue experimentation would have to include: assessing morphological changes in any target tissue; making/using a device that measures said morphological changes within a mammalian tissue; making/using a sensor that evaluates a multivalent binding response in tissue in vivo; and/or visually inspecting for a wheal and flare reaction in any tissue in vivo. Therefore, Claims 7-11 and 14 are rejected under 35 U.S.C. 112, first paragraph, because the specification does not provide enabling guidance for these claims and they fail to meet the enablement requirement.
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.
Claims 1-6, 12-13, 15, 17 and 20-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Soliemanpour et al., Appl Microbiol Biotechnol, 99: 10467-10480, 2015 as evidenced by Wilgus et al., Advances in Wound Care, Vol. 3, No. 4: 356-365, 2013 and Gupta et al., 2025 eLife.
MPEP §2131.01 provides guidance as to 35 U.S.C. 102 rejections over multiple references. Such rejection has been held to be proper when the extra references are cited to: (C) Show that a characteristic not disclosed in the reference is inherent. The MPEP states: “To serve as an anticipation when the reference is silent about the asserted inherent characteristic, such gap in the reference may be filled with recourse to extrinsic evidence. Such evidence must make clear that the missing descriptive matter is necessarily present in the thing described in the reference, and that it would be so recognized by persons of ordinary skill.” Continental Can Co. USA v. Monsanto Co., 948 F.2d 1264, 1268, 20 USPQ2d 1746, 1749 (Fed. Cir. 1991) (The court went on to explain that “this modest flexibility in the rule that 'anticipation' requires that every element of the claims appear in a single reference accommodates situations in which the common knowledge of technologists is not recorded in the reference; that is, where technological facts are known to those in the field of the invention, albeit not known to judges.” 948 F.2d at 1268, 20 USPQ at 1749-50.). Note that the critical date of extrinsic evidence showing a universal fact need not antedate the filing date. See MPEP §2124.
The Wilgus and Gupta references are relied upon solely as showing an inherent characteristic: the universal fact that mast cells exist within organ tissues, and specifically the dermis (as evidenced by Wilgus) and spleen (as evidenced by Gupta) of mammals. Therefore, the subcutaneous injection that is disclosed in the Soliemanpour reference inherently results in contact with “at least one endogenous mast cell in situ” as required by independent claims, Claims 1, 20 and 21.
Regarding Claims 1, 15 and 17, the Soliemanpour prior art teaches methods of testing a new vaccine for Mycobacterium tuberculosis infection comprising providing to mice two affinity reagent constructs comprising ESAT6:HspX:Fcγ2a or ESAT6:HspX:His (pg. 10470, second to last paragraph). The ESAT6:HspX:Fcγ2a construct anticipates the Fc epsilon R1 receptor binding domain of the instant claim, and comprises at least one additional moiety capable of binding an analyte – namely, the Mycobacterium tuberculosis antigen of instant claim 15; and more specifically the ESAT6 of instant claim 17. It should be noted that the instant disclosure teaches IgE antibodies bind to what is known as the Fc epsilon Rl receptor on the surface of tissue mast cells (paragraph [0065]). Therefore, the Fc receptor moiety binds to the mast cells as claimed.
The Soliemanpour prior art teaches mice were immunized by subcutaneous injection which leads to “contacting at least one endogenous mast cell in situ and present within a target tissue of …[a]… mammal with said reagent construct”, since the Wilgus prior art teaches mast cells reside in high numbers in the skin (Abstract, first line). The Soliemanpour prior art teaches performing an assessment by determining Th immune response (pg. 10471 section having that subtitle) and Th1 immune response (pg. 10471 section having that subtitle) as part of a multivalent tissue response. Specifically, the prior art teaches: “ESAT6:HspX:Fcγ2a-stimulated splenic cells from mice immunized with ESAT6:HspX:Fcγ2a had significantly higher levels (p<0.001) of IFN-γ and IL-12 secretion than the ESAT6:HspX:His, BCG, or PBS immunized groups (Fig. 7a, b). Mice immunized with ESAT6:HspX.His also had a significantly higher level of IFN-γ than BCG and PBS (p<0.01)” (paragraph bridging pgs. 10471-10472). The authors conclude: “The ESAT6:HspX:Fcγ2a could be used as a subunit TB vaccine for human use. It is simple to produce in the P. pastoris expression system, easy to purify, and cost-effective” (pg. 10479).
Regarding Claim 2, the Soliemanpour prior art teaches delivering the affinity reagent construct into a skin of said mammal, wherein it teaches subcutaneous injection (pg. 10470, section titled ‘Subunit vaccines: preparation and immunogenicity’). As stated above, this also teaches contacting at least one endogenous mast cell in situ.
Regarding Claim 3, the Soliemanpour prior art teaches delivering the ESAT6:HspX:Fcγ2a affinity reagent construct into the spleen tissue of the immunized mice. While the Soliemanpour prior art does not teach the spleen as having about 125 to 20,000 mast cells per cubic millimeter it should be noted that there is no positively recited step for assessing mast cells in the instant claim. Nonetheless, the Gupta prior art teaches the scientific fact that airway transfer of mast cells into mycobacterium tuberculosis-infected (Mtb) mice leads to increased Mtb dissemination within the spleen (pg. 2, last paragraph). Gupta further demonstrate that even within B6 mast cell deficient Mtb mice, mast cells are prevalent in the spleen, but adoptive transfer of mast cells leads to increased spleen mast cell numbers (Fig. 5E). Thus, the Mtb immunization taught by Soliemanpour et al., in mice that are not deficient for mast cells, inherently leads to mast cells within the spleens.
Regarding Claim 4, the Soliemanpour prior art teaches delivering comprising subcutaneous injection (pg. 10470, section titled ‘Subunit vaccines: preparation and immunogenicity’) which is equivalent to the method further comprising performing delivery the instantly-elected “intradermal injection” of the claim.
Regarding Claim 5, the subcutaneous injection as taught by Soliemanpour teaches delivering of the affinity reagent construct into the dermal layer.
Regarding Claim 6, the Soliemanpour prior art teaches evaluating the production of IFN-gamma and IL-12 from activated splenocytes (pg. 10471, last paragraph). This teaches evaluating the target tissue for “at least one physiological change”, as claimed.
Regarding Claim 12, the construct that the Soliemanpour reference teaches is a recombinantly expressed fusion protein. Peptide bonds between the elements are covalent. Therefore, the construct teaches the instantly-elected “covalent conjugation”.
Regarding Claim 13, the construct taught by Soliemanpour is created (a.k.a. fashioned from) a moiety comprising the instantly-elected “receptor binding molecule”. Specifically, the construct comprises: “the esxA (ESAT-6), a linker, hspX, and a constant region of the Fc fragment of mouse IgG2a” (pg. 10468, second to last paragraph and Figure 1). The reference discloses the Fc fragment is from “Fcγ receptors (FcγR) on antigen-presenting cells (APCs) such as myeloid and plasmacytoid dendritic cells (DCs), monocytes, and macrophages” (same page, fifth paragraph). Thus, the construct comprises a receptor binding molecule.
Regarding Claim 15 and 17, the analyte that the Soliemanpour prior art is detecting the presence of is a Mycobacterium tuberculosis antigen, and is specifically the ESAT-6 antigen of instant claim 17.
Regarding Claims 20 and 21, the method of Soliemanpour teaches selecting an analyte indicative of said Mtb pathology, namely, the Mtb antigen ESAT-6. Soliemanpour et al. provide at least one affinity reagent construct comprising at least one Fc epsilon R1 receptor binding domain and at least one additional moiety capable of binding said analyte: the ESAT6:HspX:Fcγ2 construct of Soliemanpour (a.k.a. affinity reagent construct of the instant claim). The methods of the prior art teach contacting at least one endogenous mast cell in situ within a target tissue of said mammal wherein it teaches delivering by subcutaneous injection (pg. 10470, section titled ‘Subunit vaccines: preparation and immunogenicity’). As stated above the Wilgus reference is relied upon as evidence that mast cells reside “in high numbers in the skin” (Wilgus et al., Abstract, line one). Specifically, the Soliemanpour prior art, inject the construct then isolate splenocytes in situ and performing an assessment of how ESAT6:HspX:Fcγ2a had significantly higher levels of IFN-γ and IL-12 than ESAT6:HspX:His, BCG, or PBS immunized groups (Fig. 7a, b). The authors conclude, the Fcγ2a-tagged protein can stimulate the higher specific Th1 responses than the other immunization groups. This anticipates the selecting an analyte, providing a construct, contacting at least one mast cell in situ within a target tissue of a mammal with said construct, and performing an assessment of independent claims 20 and 21.
The methods of the invention fail to distinguish over the methods disclosed in the prior art, therefore Claims 1-6, 12-13, 15, 17 and 20-21 are rejected.
Conclusion
No claim is allowed.
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/STACEY N MACFARLANE/Examiner, Art Unit 1675