DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election of in vivo contact as the species of method, dendritic cells as the species of APC, TLR9 as the species of TLR agonist, are acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicant indicates that the elected species read on all claims except 2-3 and 7. However, claims 26-28, 30-32, and 39 depend from claims 2-3, which is the non-elected in vitro embodiment, and are also withdrawn from consideration.
Claims 1, 4-6, 8-10, 13-17, and 38 read on the elected invention and are being acted upon.
Claims 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 5-6, 8-10, 13-17, and 38 are rejected under 35 U.S.C. 101 because claimed invention is directed to a law of nature without significantly more. The claim(s) recite(s) cell cell contact and/or transfer of soluble material in vivo from one or more fibroblasts to APCs. This judicial exception is not integrated into a practical application because this is a physiological process that occurs naturally in vivo in the human body. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim does not recite any method step, such as administering a fibroblast, that distinguishes from the process that occurs naturally. For example, peripheral blood APCs such as macrophages, dendritic cells, or B cells would naturally circulate throughout the body and tissues and be in contact with fibroblasts during physiological processes including infection or inflammation Likewise, fibroblasts circulate during physiological processing including cancer and would be in contact with APCs. Furthermore, fibroblasts naturally act a sentinels in response to TLR agonists that are present during microbial infection (see Bautisa-Hernandez). Thus, the limitation that the fibroblasts are ”pretreated” with TLRs also does not serve to integrate the judicial exception, since fibroblasts in vivo would naturally be “pretreated” with TLRs during infection, for example. Thus, the present claim merely describe a physiological process, i.e. a law of nature that occurs in vivo in the human body during physiological process that occur during autoimmune disease, inflammation or infection. The claims do not recite any additional method steps that integrate the judicial exception into a practical application.
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, 4-6, 8-10, 13-17, and 38 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 recites a method of inhibiting a pathological immune response, comprising cell to cell contact and/or transfer of soluble materials. The claim does not recite an active step, i.e. contacting cells or administering cells. It is therefore unclear if the pathological immune response itself comprises cell cell contact, or whether the method induces the cell cell contact to be initiated (via administration or co-culturing cells, for example). In other words, it is not clear if the method requires inhibiting pathological cell-cell contact and/or transfer of soluble material, or whether the method inhibits a pathological immune response by allowing for cell-cell contact and/or transfer of soluble material. For example, does the claimed method encompass a method wherein fibroblasts are administered in vivo such that they contact APCs and/or transfer soluble materials to APCs? Or is the claimed method a method wherein fibroblasts are administered to inhibit pathological cell-cell contact and/or transfer of soluble materials to APCs. The scope of the claims cannot be established.
Claim 17 contains the trademark/trade name “LyoVecTM” Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a source of a cationic lipid and, accordingly, the identification/description is indefinite.
Claim 17 is also indefinite in the recitation of PolyTC, which is not a known TLR3 agonist. The specification discloses the use of Poly:IC as a TLR3 agonist, and amendment to the claim to recite poly:IC would be remedial.
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 1, 4-6, 8-10, 13-17, and 38 are rejected under 35 U.S.C. 112, 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 specification disclosure is insufficient to enable one skilled in the art to practice the invention as claimed without an undue amount of experimentation. Undue experimentation must be considered in light of factors including: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill in the art, the level of predictability of the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention, see In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) states, “The 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.” “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” (MPEP 2164.03). The MPEP further states that physiological activity can be considered inherently unpredictable. With these teachings in mind, an enabling disclosure, commensurate in scope with the breadth of the claimed invention, is required.
The present claims are directed to inhibiting any pathological immune response comprising cell to cell contact and/or transfer of soluble materials from one or more fibroblasts to one or more antigen presenting cells, wherein the cell to cell contact and/or transfer reduces antigen presenting cell activity and/or reprograms said antigen presenting cells. This encompasses a genus of different pathological immune response. For example, the claims encompass inhibiting autoimmune disease, graft rejection, or autoimmune reactions. However, pathological immune responses would also encompass HIV infection which reduces T cell levels and leads to chronic, undesired inflammation. Likewise, it would encompass cancers of the lymphoid system. The claims also encompass a large genus of different fibroblast cells and antigen presenting cells stimulated with a genus of different culture systems or TLR agonists. The claims also encompass reducing a genus of activities or reprograming the antigen presenting cells in any manner, i.e. increasing or decreasing differentiation pathways, modulating cytokine secretion, surface molecule expression, or antigen presentation.
The state of the art is such that the effect of fibroblast cells on APCs and immune function is highly unpredictable. For example, in some situations fibroblasts can have a tolerogenic effect on dendritic cells by reducing co-stimulatory molecules and pro-inflammatory cytokine secretion, while in other circumstances, fibroblasts have the opposite effect on APCs and can promote dendritic cell maturation, migration, and expansion of proinflammatory cells (See Schirmer and Khosravi-Maharlooei, of record). Shirmer teaches that during psoriasis (i.e. an autoimmune reaction) fibroblasts can secrete PGE2 that promotes IL-23 secretion by dendritic cells and perpetuates pathogenic immune response in psoriasis. Likewise, Hafner teaches that fibroblasts exposed to TLR agonists such as polyI:C can induce autoimmune responses. Furthermore, the role of immune modulation in treating any type of pathogenic immune response, such as during chronic infection is also highly unpredictable. For example, modulating this response to treat HIV is unpredictable due to the potential to also weaken HIV specific responses (see Chevalier et al., 2013). Furthermore, the claims encompass treating any autoimmune disease, and the state of the art is such that a therapy that benefits one autoimmune disease will sometimes make another disorder worse (see Progress in Autoimmune Diseases Research, 2005, page 55, of record).
Thus, based on the breadth of the claims and the unpredictability of the art, the instant specification must provide a sufficient and enabling disclosure commensurate in scope with the instant claims. The specification discloses an example wherein dermal fibroblasts or LPS treated dermal fibroblasts are co-cultured with immature dendritic cells in vitro, wherein the dendritic cells co-cultured with the fibroblasts exhibit reduced expression of co-stimulatory molecules and IL-12 production. However, this is not commensurate in scope with the instant claims. No guidance or examples of reducing pathological immune responses or autoimmune disease are provided. Likewise, the present claims encompass any type of fibroblast that contact any type of APC, wherein the fibroblast is treated under a genus of conditions with a genus of different TLR agonist. No guidance is provided regarding which types of fibroblasts, or TLR agonists would be suitable for which pathological reactions. Thus, given the unpredictability of the art, the breadth of the claims, and the lack of guidance provided by the instant specification, it would require undue experimentation to practice the method of the instant claims.
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.
Claim(s) 1, 4-6, 8-10, and 38 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by 7,491,388 (of record).
The ‘388 patent teaches a method of reducing an immune response to a transplant or a GVHD response (i.e. a pathological immune response) comprising systemically administering fibroblasts to an individual (see columns 1-6, in particular). The method would inherently involve cell-cell contact and/or transfer of soluble material to APCs in vivo, and or reduce APC activity and/or reprogram APCs (by reducing costimulatory molecules or cytokines), since it is identical to the claimed method.
Claim(s) 1, 4-6, 8-10, and 38 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Khosravi-Maharlooei, 2016 (of record).
Khosravi-Maharlooei teaches a method of comprising administering fibroblasts to an individual (in-vivo) wherein the fibroblasts contact dendritic cells and upregulate inhibitory molecules such as PD-L1 (i.e. reprograms the dendritic cells. see page 24-25 and 30 particular). The method would inherently inhibit a pathological immune response or an autoimmune “reaction” and would inherently involve cell-cell contact and/or transfer of soluble material to APCs in vivo and reduce APC reduce cytokines, since it is identical to the claimed method.
Claim(s) 1, 4-6, 8-10, and 38 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 20180195044 (it is noted that the ‘044 publication is the PG-PUB of the application issued as U.S. Patent 11,034,934).
The ‘044 publication teaches a method of providing anti-inflammatory activity (inhibiting pathological immune response) comprising systemically administering to an individual cultured fibroblasts (see paragraphs 33-35, in particular). The method would inherently involve cell-cell contact and/or transfer of soluble material to APCs in vivo, and or reduce APC activity and/or reprogram APCs (including dendritic cells, and by modulating costimulatory or cytokines), since it is identical to the claimed method.
Claim(s) 1, 4-6, 8-10, 13-17, and 38 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Selden, 1987, as evidenced by Malinovskaya, 2019.
Selden teaches a method of comprising intraperitoneally or subcutaneously administering to an individual cultured fibroblasts. Selden teaches that the fibroblasts are pre-treated with a plasmic vector (pBR322 vector) prior to administration (See Fig. 1, in particular). As evidenced by Malinovskaya, said vector inherently comprises CpG oligonucleotides that act as TLR9 ligands (see Fig. 2, in particular). The method would inherently inhibit pathological responses such as autoimmune reactions and would inherently involve cell-cell contact and/or transfer of soluble material to APCs in vivo, and would reduce APC activity and/or reprogram APCs (including dendritic cells, and by modulating costimulatory and/or cytokines) since it is identical to the claimed method.
Claim(s) 1, 4-6, 8-10, 13-17, and 38 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by 12,133,870 or 11,975,030.
The patents teach a method comprising administering a fibroblast to an individual. The patents teach that the fibroblasts are pretreated with a TLR-9 agonist such as ODN2006. The method would inherently inhibit pathological autoimmune reactions and would inherently involve cell-cell contact and/or transfer of soluble material to APCs in vivo, and reduce APC activity and/or reprogram APCs (including dendritic cells, and by modulating costimulatory and/or cytokines) since it is identical to the claimed method.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4-6, 8-10, and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 12,090,174, 11,959,102, 11,878,037, or 11,034,934. Although the claims at issue are not identical, they are not patentably distinct from each other because the patents claim administering to an individual fibroblast cells. The method would inherently inhibit pathological autoimmune reactions and would inherently involve cell-cell contact and/or transfer of soluble material to APCs in vivo, and reduce APC activity and/or reprogram APCs (including dendritic cells, and by modulating costimulatory and/or cytokines) since it is identical to the claimed method.
Claims 1, 4-6, 8-10, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18,570,530, 18/561,979, 17/907,115, 18/005,065, 18/040,345, 17/999,588, 17/998,183, 17/996,102, 17/999,575, 17/996,392, 17/999,583, 17/996,033, 17/996,109, 17/754,812, 18/057,262, 17/754,807, 17/906,883, 17/760,318, 17/904,180, 17/757,387, 17/757,383, 17/755,278, 17/754,106, 17/755,837, 17/755,275, 17/755,834, 17/755,051, 17/757,309, 17/757,314, 17/738,584, 17/753,491, 17/753,487, 17/596,889, 17/594,752, 17/594,729, 17/594,730, 17/310,007, 17/309,177, 17/309,178, 17/309,649, 17/309,176, 17/052,859, 18/603,451, 17/271,529, 16/913,860, 18/905,224, or 19/020,418 (reference applications). Although the claims at issue are not identical, they are not patentably distinct from each other because the applications claim administering to an individual fibroblast cells. The method would inherently inhibit pathological autoimmune reactions and would inherently involve cell-cell contact and/or transfer of soluble material to APCs in vivo, and reduce APC activity and/or reprogram APCs (including dendritic cells, and by modulating costimulatory and/or cytokines) since it is identical to the claimed method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
It is noted that many of the above applications and patents have priority dates that precede the filing date of the instant application and would qualify as prior art under 102(a)(1) or 102(a)(2). In the interest of brevity, and since the prior art rejections are all of a similar nature, only the oldest publication of these applications is cited as a 102(a)(1) rejection above.
Claims 1, 4-6, 8-10, 13-17, and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 12,133,870 or 11,975,030. Although the claims at issue are not identical, they are not patentably distinct from each other because the patents claim administering to an individual fibroblast cells. The patents claims that said fibroblasts are activated by exposure to TLR ligands. The patents claim ODN2006 as the TLR9 ligand, or alternately selecting from known TLR9 agonists would be routine and well within the purview of the ordinary artisan. The method would inherently inhibit pathological autoimmune reactions and would inherently involve cell-cell contact and/or transfer of soluble material to APCs in vivo, and reduce APC activity and/or reprogram APCs (including dendritic cells, and by modulating costimulatory and/or cytokines) since it is identical to the claimed method.
Claims 1, 4-6, 8-10, 13-17, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 17/904,606, 18/042,323, 17/905,961, or 18/618,017 (reference applications). Although the claims at issue are not identical, they are not patentably distinct from each other because the applications claim administering to an individual fibroblast cells. The applications claims that said fibroblasts are activated by exposure to TLR ligands. The applications claim ODN2006 as the TLR9 ligand, or alternately selecting from known TLR9 agonists would be routine and well within the purview of the ordinary artisan. The method would inherently inhibit pathological autoimmune reactions and would inherently involve cell-cell contact and/or transfer of soluble material to APCs in vivo, and reduce APC activity and/or reprogram APCs (including dendritic cells, and by modulating costimulatory and/or cytokines) since it is identical to the claimed method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dan Kolker, can be reached at telephone number 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644