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 .
DETAILED ACTION
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 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.
Election/Restrictions
Applicant’s election with traverse of Group II, claims 8, 9 and 12, in the reply filed on Jan. 20, 2026 is acknowledged. Claims 1, 3, 15-22, 27, 29 and 30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention. The traversal is on the grounds that the groups of inventions share the special technical feature. This is not found persuasive because as indicated by the rejections below, the groups do not share the special technical feature which contributes over the prior art at the time the invention was made.
The requirement is still deemed proper and is therefore made FINAL.
Claims 8, 9 and 12 are presented for examination on the merits.
Status of the Claims
Claims 1, 3, 8, 9, 12, 15-22, 27, 29 and 30 are currently pending.
Claims 1, 3, 15-22, 27, 29 and 30 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.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 2, 4-7, 10, 11, 13, 14, 23-26 and 28 are cancelled.
New claims 29 and 30 have been added.
Claims 8, 9 and 12 have been considered on the merits.
Drawings
The disclosure is objected to because of the following informalities:
The drawings are objected to because of the following informalities: there is a statement in the specification that there are color drawings in 0029, and there is description of color in the specification of Fig. 2E and 2F in 0032 and the various colors cannot be distinguished from each other since the figures are in black and white.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities: the use of trademarks.
The use of the terms: Qtracker™ in 0035-0036, 0038, 0042-0043, 0083, 0085-0087, 0100, 0102-0104, 0109, 0112-0113; MoFlo Astrios® Cell Sorter in 0035 and 0038-0039, 0085; Dynabeads™ in 0082; Perkin Elmer Filtermate® harvester in 0082; Alexa Fluor® 700 in 0083; FACSLyric™ in 0084; RNeasy® Minikit in 0085; KAPA® Stranded RNA-Seq Kits in 008; Illumina HiSeq™ 4000 in 0085; C1000 Touch™ Thermal Cycler in 0086; TransIT-2000® in 0090; Leica® SP8 upright confocal microscopy in 0090, 0092; Tween® 20 in 0091; Triton™ X-100 in 0091; Alexa Fluor® 488 in 0092; VectaShield® medium in 0092; Imaris® Bitplane software 9.1.2 in 0092; Liberase® in 0093; GraphPad® in 0094, which are a trade names or a marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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 8, 9 and 12 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 administering mesenchymal stromal cells (MCSs) by an IV (intravenous) injection to a mouse model of lung inflammation, does not reasonably provide enablement for the suppression of a T cell response in all subjects of any species by administering by any means a therapeutically effective amount of isolated processing bodies (p-bodies) or MSCs. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). 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 USPQ2sd 1404). Clearly, the 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). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (2) the breadth of the claims:
The claims are drawn to a method of suppressing a T cell response in a subject by administering a therapeutically effective amount of a pharmaceutical composition containing isolated p-bodies or MSCs and a pharmaceutically acceptable carrier. Thus, the claims taken together with the specification imply that any subject of any species can have a T cell response suppressed by any mode of delivery of a therapeutically effective amount of isolated p-bodies or MSCs.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
The state of the prior art of cell therapy and cellular vesicle therapy for suppressing T cell responses in a subject was highly unpredictable before the effective filing date of the claimed invention. Inventions using cell therapy or cellular vesicles bear a heavy responsibility to provide supporting evidence because of the unpredictability in biological responses to such therapeutic treatments.
While cell therapy has been used to suppress immune responses, cell therapy in general continues to be unpredictable as supported by numerous teachings available in the art. For instance, Caplan et al. (Frontiers in Immunology, 2019) (ref. of record) states the “translation into clinical practice has proven considerably more difficult” for mesenchymal stromal cells (abstract). Caplan states there is no consensus on the optimal method for MSC delivery (pg. 2 Col. 2 para. 2 and Fig. 1) and “that different clinical indications and pathologies will require different delivery routes for optimal therapeutic efficacy (pg. 2 Col. 2 para. 2). Klinker et al. (World Journal of Stem Cells, 2015) (ref. of record) reports that the performance of MSC-based immunotherapies in treating inflammatory disorders and autoimmune diseases in clinical trials has been inconsistent (pg. 557 Col. 1 para. 2 and pg. 562 Col. 2 para. 3). Accordingly, inventions targeted for the cell therapy of inflammatory disorders and autoimmune diseases bear the responsibility to provide supporting evidence because of the unpredictability in biological responses to the cells being administered.
The state of the prior art of p-body for suppressing T cell responses in a subject was highly unpredictable before the effective filing date of the claimed invention. For instance, Luo et al. (Biochemistry, 2018) (ref. of record) reports that the actual function of p-bodies is unknown and the properties and composition of p-bodies is not clearly understood (abstract, pg. 2425 Col. 1 last para., and pg. 2429 last para.). There appears to be a lack of information in the art on administering p-bodies for any form of therapy in a subject. Additionally, the state of the prior art of administering exosomes, similar cellular vesicles, was highly unpredictable before the effective filing date of the claimed invention. For example, Tzng teaches exosome therapies face several challenges including short half-life, poor standardization of exosome collection and biopharmaceutical regulation (pg. 1 para. 2). Tzng teaches exosomes as a biological therapy and personalized medicine faces numerous challenges (pg. 1 para. 1 and Fig. 2). Although, exosomes are not exactly the same as p-bodies, they are cellular vesicles containing proteins and RNA like p-bodies, and one skilled in the art would reasonably predict similar challenges would exist for p-bodies.
Accordingly, inventions targeted for the cell therapy and cellular vesicle therapy of inflammatory disorders and autoimmune diseases bear the responsibility to provide supporting evidence because of the unpredictability in biological responses to particular cell types being administered. Thus, as the state of the art stands, the treatment of inflammatory disorders and autoimmune diseases by cell therapy and isolated p-bodies is highly unpredictable. In the instant case, the applicants have provided only a specific example of treatment of a mouse model of lung inflammation with human cord tissue-derived MSC.
The high degree of unpredictability associated with the claimed method underscores the need to provide teachings in the specification that would provide the skilled artisan with additional modes of administration, additional species of subject such as non-mammal species, and subjects with additional inflammatory disorders and autoimmune diseases conditions that achieve suppression of T cell response other than IV injection, mice and lung inflammation. Additionally, evidence that isolated p-bodies can be administered to effectively suppress a T cell response in a subject has not been provided. There appears to be no basis for extending or generalizing the results described in the specification with respect to administering by any mode MSCs or isolated p-bodies to all inflammatory disorders and autoimmune diseases conditions to any species of subject.
(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 and (7) the presence or absence of working examples:
The instant specification provides working examples and guidance for the use of the instantly claimed method for the IV injecting of hCT-MSC (human cord tissue-derived MSCs) into mice prior to administering LPS to induce lung inflammation to suppress the T cell response (Example 4). Additionally, data is presented in Example 1 showing that hCT-MSC suppressed TH cell activation in mouse splenocytes and in human blood in vitro (0098 of published application). Furthermore, the specification speculates that after monocytes and macrophages engulf the components of hCT-MSCs the genes responsible for presenting antigens and activating T cells are down-regulated including genes implicated in rheumatoid arthritis and primary immunodeficiencies (0113 of published application).
However, the specification does not provide any guidance for the use of the instantly claimed method for administering isolated p-bodies and pharmaceutically acceptable carrier to any subject other than mice by any other means than IV injection to suppress a T cell response. The applicants have provided no additional data demonstrating the claimed method using isolated p-bodies would be effective in suppressing a T cell response in a subject. The applicants have provided no additional data demonstrating the claimed method using MSCs would be effective in suppressing a T cell response in all species by all modes of administration.
Therefore, there is no conclusive evidence in the instant disclosure to indicate that the instantly claimed method can be used to suppress a T cell response in all species by administrating isolated p-bodies or MSCs by all modes of administration.
(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.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8, 9 and 12 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.
In claim 8, line 3, the phrase “the pharmaceutical composition of claim 1”, renders the claim and its dependents indefinite, since the claim depends on a non-elected claim, and, therefore, is incomplete.
All other claims depend directly or indirectly from rejected claims and are, therefore, also rejected under USC 112 for the reasons set forth above.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 8, 9 and 12 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Mohapatra et al. (WO 2009/042173 A1)(ref. of record) as evidenced by Luo et al. (Biochemistry, 2018) (ref. of record).
With respect to claim 8, Mohapatra teaches a method of suppressing a T cell response or reducing an inflammatory response in a subject in need thereof by administering a therapeutically effective amount of a pharmaceutical composition of mesenchymal stem cells and a pharmaceutically acceptable carrier (pg. 23 lines 18-32, pg. 25 lines 24 and claims 11 and 23). The MSCs inherently contain processing bodies (p-bodies) as evidenced by Luo. Luo reports that p-bodies are conserved in eukaryotes (pg. 2424 para. 1). With respect to claim 9, Mohapatra teaches the method where the immune cells are T helper cells (claims 11 and 17). With respect to claim 10, Mohapatra teaches the method where the inflammatory response is in lung tissue (claims 21 and 23).
Therefore, the reference anticipates the claimed subject matter.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 8, 9 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Mohapatra et al. (WO 2009/042173 A1)(ref. of record) as evidenced by Luo et al. (Biochemistry, 2018) in view of Betancourt (US 2014/0017787 A1).
With respect to claim 8, Mohapatra teaches a method of suppressing a T cell response or reducing an inflammatory response in a subject in need thereof by administering a therapeutically effective amount of a pharmaceutical composition of mesenchymal stem cells and a pharmaceutically acceptable carrier (pg. 23 lines 18-32, pg. 25 lines 24 and claims 11 and 23). The MSCs inherently contain processing bodies (p-bodies) as evidenced by Luo. Luo reports that p-bodies are conserved in eukaryotes (pg. 2424 para. 1). With respect to claim 9, Mohapatra teaches the method where the immune cells are T helper cells (claims 11 and 17). With respect to claim 10, Mohapatra teaches the method where the inflammatory response is in lung tissue (claims 21 and 23).
Mohapatra does not teach the method where the subject suffers from neuroinflammation, rheumatoid arthritis and/or a primary immunodeficiency as recited in claim 12. However, Betancourt teaches a similar method of suppressing inflammation or a T cell response by administering to the subject a therapeutic effective amount of mesenchymal stem cells (abstract, 0002, 0008, 00018 and 0046). Betancourt further teaches a method of suppressing an immune response by inhibiting T cells in a subject where the subject suffers from rheumatoid arthritis, immunodeficiency, and acute lung injury (0046, 0049-0050, and 0062). Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the method of Mohapatra to include subject with additional diseases or conditions that would benefit from suppressing a T cell response including rheumatoid arthritis and a primary immunodeficiency as taught by Betancourt for the benefit of treating addition known inflammatory and immune conditions. It would have been obvious to one of ordinary skill in the art to modify the treatment method Mohapatra to include subjects suffering from neuroinflammation, rheumatoid arthritis and a primary immunodeficiency, since these conditions are known to benefit from T cell suppression as taught by Betancourt. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to Mohapatra, since Betancourt teaches administering MSCs to treat inflammatory and immune conditions and Mohapatra teaches suppressing a T cell response or reducing an inflammatory response in a subject.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY ANN CORDAS whose telephone number is (571)272-2905. The examiner can normally be reached on M-F 9:00-5:30 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached on 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/EMILY A CORDAS/Primary Examiner, Art Unit 1632