DETAILED ACTION
This action is in reply to papers filed 11/17/2023. Claims 1-13 are pending and examined herein.
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 .
Examiner’s Note
All paragraph numbers throughout this office action, unless otherwise noted, are from the US PGPub of this application US20240075072A1, Published 3/7/2024.
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 1-11 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. Note that the instant rejection is solely based on Applicant’s claiming of ‘preventing ….an inflammatory disease’ in claim 1.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). The court in Wands states that “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 104). 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 weighting many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation required is “undue” include, but are not limited to:
• (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
Furthermore, the USPTO does not have laboratory facilities to test if an invention will function as claimed when working examples are not disclosed in the specification. Therefore, enablement issues are raised and discussed based on the state of knowledge pertinent to an art at the time of the invention. And thus, skepticism raised in the enablement rejections are those raised in the art by artisans of expertise.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Amount of Direction Provided by Inventor/Working Examples: Relevant to the instant rejection, the specification at para. 194 discloses it was investigated whether SOD3-transfected MSCs has an inflammation-modulating effect in the body, on the basis of the regulatory effect of MSCs overexpressing SOD3 on T cell proliferation and differentiation. SOD3-transfected MSCs was applied to the imiquimod (IMQ) model to the shaved back skin in mice every day to induce skin inflammation responses, a model which is known to induce psoriasis-like acute and aggressive dermatitis by activating signaling of the innate immune system. As shown in FIG. 11 , compared with a control without IMQ application, the mice with the IMQ application without subcutaneous injection of MSCs started to display signs of erythema, scaling, and thickening, which can be confirmed by the naked eye, accompanied by inflammation symptoms, after 2-3 days. Such symptoms were clearly observed 6 days after the start of the experiment (Day 6), and continued until 12 days after the start of the experiment (Day 12). The mice injected with untreated MSCs (MSC) or LacZ-transfected MSCs (LACZ-MSC) showed a tendency to alleviate IMQ-induced skin symptoms. Meanwhile, the symptoms, such as erythema and scaling, were observed to be apparently reduced to the naked eye in the mice injected with SOD3-transfected MSCs (SOD3-MSC) compared with the mice injected with MSCs or LACZ-MSCs.
The specification discloses these results, inter alia, indicate that MSCs, which overexpress SOD3 by SOD3 transfection, had a significant effect in the alleviation of skin inflammation compared with general MSCs (Pg. ,para. 198). The specification also observed results which inventors indicate that the inflammation-modulating action of MSCs was increased more effectively due to SOD3 introduction, suggesting that the symptoms of inflammation diseases can be alleviated by complexly regulating the expressions and actions of various cytokines (Pg. ,para. 208). In another experiment, the inventors observed that SOD3-MSCs have a protective function from cellular stress (Pg. ,para. 214).
Critically, each example provided by the specification discloses an alleviating effect (i.e. treating) of applying SOD3-transfected MSCs to a subject in need thereof. None of these examples show a preventative effect. This is problematic. Given the high level of required effect, a high level of evidence showing prevention is separately required. Examiner notes that one skilled in the art could not practice the claim to achieve the results of preventing an inflammatory disease, because the specification lacks the critical steps necessary in presenting some type of predictable response in a population of hosts deemed necessary to prevent inflammatory disease. Reasonable guidance with respect to preventing inflammatory disease relies on quantitative analysis from defined populations which have been successfully pre-screened and are predisposed to inflammatory disease or have had inflammatory disease. The essential element towards the validation of a preventive therapeutic is the ability to test the drug on subjects monitored in advance of the onset of inflammatory disease in a subject afflicted and link those results with subsequent histological confirmation of the presence of an inflammatory disease. This irrefutable link between antecedent drug and subsequent knowledge of the prevention of the disease is the essence of a valid preventive agent. Such is not provided in the instant specification.
The State of the Prior Art: Bandgar (Bioorg Med Chem. 2010 Aug 15;18(16):6149-55) teaches inflammation is the body's way of dealing with infections and tissue damage, but there is a fine balance between the beneficial effects of inflammation cascades and their potential for long-term tissue destruction. If they are not controlled or resolved, inflammation cascades can lead to the development of diseases such as chronic asthma, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and psoriasis. Within many inflammation cascades or pathways there are often pivotal molecular targets that, when antagonized or neutralized, block the output of the pathway. Historically, at least over the past 20 years in the modern era of target-based drug discovery, a relatively small number of pivotal targets have been identified that have yielded any successful anti-inflammatory drugs (Pg. 6150, Col. 1, para. 1). To this point, Marie et al. (Mult Scler. 2025 Dec 26:13524585251398381.) teach that in 2020, nearly 3 million people were living with multiple sclerosis (MS) worldwide. Costs to affected individuals, their families, health systems, and society remain high.2 Considerable progress has been made in understanding genetic and environmental risk factors for MS, and its pathobiology. The expanding array of disease-modifying therapies (DMTs) reflects highly effective global scientific collaboration. Yet, MS still cannot be prevented (Pg. 1, Col. 1). Similarly, Sharma et al. (Oriental Journal of Chemistry 38.4 (2022).) teach psoriasis is a multifaceted, challenging illness for which several innovative therapeutics have emerged in recent years. Despite advancements in targeted medicines, Sharma teaches psoriasis represents a manageable but not preventable condition (Pg. 945, Col. 1, para. 1). CA Mattison (Hamilton, Canada: McMaster Health Forum, November 22, 2018.) simply discloses irritable bowel syndrome (IBD) is not preventable, given the role of genetics and environmental factors (paragraph bridging Pg. 10 and Pg. 11).
In sum, the art makes clear that while inflammatory diseases are treatable, they are not preventable. Therefore, it is reasonable to conclude that a pharmaceutical composition for the purposes of preventing an inflammatory disease in a subject was not enabled by the specification or the art.
The level of Predictability in the Art/Conclusion: The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue. Due to the lack of guidance or evidence in the specification or in the art regarding preventing inflammatory diseases, it would have required undue experimentation for one skilled in the art at the time of the invention to practice the invention, as claimed.
Claim Rejections - 35 USC § 101/112 (b)- “Use Claims”
MPEP 2173.05 (q) (I) states that in view of the split of authority as discussed above, the most appropriate course of action would be to reject a “use” claim under alternative grounds based on 35 U.S.C. 101 and 112 . As such, “use” claim 12 is rejected under 35 U.S.C. 101 AND 35 U.S.C. 112(b).
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.
Claim 12 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because claim 21 is not a proper process claim under 35 U.S.C. 101. Per MPEP 2173.05 (q), in a case using similar “use” language, the court in In Clinical Products Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966), held the following claim was not a proper process claim under 35 U.S.C. 101: “The use of a sustained release therapeutic agent in the body of ephedrine absorbed upon polystyrene sulfonic acid.” Appropriate correction is required.
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.
Claim 12 is 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 pre-AIA the applicant regards as the invention.
At issue for the purpose of instant rejection is that the claims are directed to the “use” of stem cells overexpressing SOD3- but do not set for any steps. Per MPEP , 2173.05 (q) 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. This position has been consistently held by the courts. 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).
Appropriate correction is required.
Claim Rejections - 35 USC § 103
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.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1- 13 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (Exp Mol Med. 2012 Sep 30; 44(9):529-35.; Ref. 20 in IDS filed 10/12/23), Gan et al. (Myotherapy. 2015 Apr;17(4):403-17.; Ref. 2 in IDS filed 10/12/23), Kim et al. (Free Radic Biol Med. 2011 Dec 1;51(11):1985-95; Ref. 5 in IDS filed 10/12/23), Tokura et al. (J UOEH. 2010 Dec 1;32(4):317-28.; Ref. 18 in IDS filed 10/12/23), Crapo et al. (U.S. Patent US6127356, Published 10/3/2000; Ref. 2 in IDS filed 10/12/23) and Crapo et al. (U.S. Patent US5994339, Published 11/30/1999; Ref. 1 in IDS filed 10/12/23 ), hereinafter referred to as Crapo (b) et al.
Claim interpretation: In view of the 112 (b) rejection above, claim 12 is being interpreted to mean a method of treating an inflammatory disease by administering stem cells overexpressing SOD3.
Yu et al. teach oxidative stress such as reactive oxygen species (ROS) within the inflamed joint have been indicated as being involved as inflammatory mediators in the induction of arthritis. Correlations between extracellular-superoxide dismutase (EC-SOD) and inflammatory arthritis have been shown in several animal models of RA. However, there is a question whether the over-expression of EC-SOD on arthritic joint also could suppress the progression of disease or not (Pg. 529, paragraph bridging Col. 1 and Col. 2). Towards this end, and with regards to claim 1, claim 12 and claim 13, Yu teach studying the effect on the synovial tissue of experimental inflammatory arthritis using EC-SOD over-expression model (Pg. 530, Col. 1, last paragraph). Yu teaches the over-expression of EC-SOD in synovial tissue, showed suppressed incidence and development of inflammatory arthritis disease. Notably, Yu teaches protective effects included the inhibition of key pro-inflammatory cytokines, such as IL-1β and TNF-α (Pg. 532, Col. 1, para. 1).
However, Yu fails to teach SOD3 is overexpressed in stem cells (as further in claim 1, claim 12 and claim 13).
Before the effective filing date of the claimed invention, Gan et al. taught exposure to ionizing radiation leads to the increased generation of reactive oxygen species (ROS) and other free radicals. Gan adds that oxidative stress after high-dose ionizing radiation has been implicated in delayed morbidity (Pg. 404, Col. 1, para. 1). Thus, Gan reasons that clinical management of ARS may benefit from improving tissue damage repair processes through the use of therapies that are directed at mitigation of inflammation caused by oxidative stress; MSCs have anti-oxidative stress. Gan notes that Superoxide dismutase (SOD) is a potent anti-oxidant enzyme that converts the superoxide anion (O2–) radical into hydrogen peroxide plus molecular oxygen. Thus, towards this end, Gan et al. describe a novel therapeutic approach to treat acute radiation syndrome (ARS) by combining the unique regenerative capabilities of umbilical cord mesenchymal stem cells (UCMSCs) (as further in claim 1, in claim 2, in claim 3 and as further in claim 12 and claim 13) with the anti-oxidative activity of SOD. Particularly, Gan examined whether systemic administration of UCMSCs transfected with adenoviruses comprising the human ECSOD3 gene (as in claim 9 and claim 10) could rescue hematopoietic failure in a mouse model of lethal irradiation (Pg. 404, Col. 1, para. 2-Pg. 404, paragraph bridging Col. 1 and Col. 2). Gan concludes that their data highlight the clinical potential of this two-pronged approach to the treatment of ARS, thereby serving as a rapid and effective first-line strategy to combat the hematopoietic failure resulting from a radiation accident, nuclear terrorism and other radiologic emergencies (Pg. 413, Col. 2, para. 2).
However, neither Yu nor Gan teach the inflammatory disease is a skin inflammatory disease (as in claim 17).
Before the effective filing date of the claimed invention, Kim et al. sought to investigate the role of EC-SOD in angiogenesis and inflammation in chronic inflammatory skin disorders such as psoriasis (Pg. 1986, Col. 1, para. 2). Kim teaches overexpressed EC-SOD reduced expression of angiogenic factors and proinflammatory mediators in hypoxia-induced keratinocytes and in ultraviolet B-irradiated mice, whereas the expression of the antiangiogenic factor tissue inhibitor of metalloproteinase-1 and anti-inflammatory cytokine interleukin-10 were increased. EC-SOD decreased new vessel formation, epidermal edema, and inflammatory cell infiltration in UVB-irradiated transgenic mice (Pg. 1960). Moreover, cells treated with recombinant human EC-SOD showed inhibited endothelial tube formation and cell proliferation. Overall, the antiangiogenic and anti-inflammatory effects of EC-SOD might be due to suppression of hypoxia-inducible factor-1α, protein kinase C, and nuclear factor-κB expression (Abstract). Furthermore, EC-SOD expression in tissue from psoriasis patients was markedly decreased in psoriatic lesional and nonlesional skins from psoriasis patients in comparison to normal skin from healthy volunteers (paragraph bridging Pg. 1992 and Pg. 1993). Together, Kim teaches these results suggest that EC-SOD may provide a novel therapeutic approach to treating angiogenic and inflammatory skin diseases such as psoriasis (as in claim 5, claim 6, claim 7 and claim 12). As noted by Tokura, psoriasis is a Th17 mediated skin disease (as in claim 4) (see Tokura Abstract).
However, none of Yu, Gan, Kim or Tokura teach the SOD3 includes the amino acid sequence defined by SEQ ID NO: 1 or SEQ ID NO: 3 (as in claim 8) or that the polynucleotide encoding SOD3 includes the nucleotide sequence defined by SEQ ID NO: 2 or SEQ ID NO: 4 (as in claim 11).
Before the effective filing date of the claimed invention, Crapo et al. taught a method of treating an inflammatory condition in a patient in need of such treatment comprising administering to the patient an effective amount of an oxidant scavenger, such as EC-SOD, under conditions such that the treatment is effected (Col. 6, lines 22-27). In fact, Crapo teaches an amino acid sequence that is 100% identical to SEQ ID NO: 1 of claim 8. The alignment between SEQ ID NO: 1(Qy, query) and the SOD3 amino acid sequence taught by Crapo et al. (Db, database) is provided below.
RESULT 5
AAY94782
ID AAY94782 standard; protein; 240 AA.
XX
AC AAY94782;
XX
DT 15-JUN-2007 (revised)
DT 12-FEB-2001 (first entry)
XX
DE Human superoxide dismutase (EC-SOD) protein sequence.
XX
KW Porphine; metal complex oxidant scavenger; inhibitor; EC-SOD; gout;
KW superoxide dismutase; myocardial infarction; stroke; acute head trauma;
KW organ reperfusion; bowel ischaemia; pulmonary infarction; glaucoma;
KW skeletal muscle reperfusion injury; central nervous system disease; AIDS;
KW dementia; stroke; amylotrophic lateral sclerosis; Parkinson's disease;
KW Huntington's disease; neurological disorder; arthritis; hypertension;
KW artherosclerosis; oedema; septic shock; pulmonary hypertension; asthma;
KW impotence; infertility; endometriosis; diabetes; pneumonia; human;
KW cystic fibrosis; sinusitis; autoimmune disease; BOND_PC;
KW superoxide dismutase 3, extracellular;
KW Superoxide dismutase 3, extracellular [Homo sapiens];
KW superoxide dismutase; extracellular-superoxide dismutase (EC 1.15.1.1);
KW extracellular-superoxide dismutase mature peptide G00-125-291; SOD3;
KW SOD3 [Homo sapiens]; superoxide dismutase 3;
KW superoxide dismutase 3 [synthetic construct];
KW superoxide dismutase 3, extracellular [synthetic construct]; GO1666;
KW GO4785; GO5507; GO5515; GO5578; GO5625; GO5802; GO6801; GO8201; GO8270;
KW GO16209; GO16491; GO46872.
XX
OS Homo sapiens.
XX
FH Key Location/Qualifiers
FT Peptide 1..18
FT /note= "Putative signal peptide"
FT Protein 19..240
FT /label= EC-SOD
FT /note= "Superoxide dismutase"
XX
CC PN US6127356-A.
XX
CC PD 03-OCT-2000.
XX
CC PF 07-JUN-1996; 96US-00663028.
XX
PR 15-OCT-1993; 93US-00136207.
PR 13-OCT-1994; 94US-00322766.
PR 07-JUN-1995; 95US-00476866.
PR 11-MAR-1996; 96US-00613418.
XX
CC PA (UYDU-) UNIV DUKE.
XX
CC PI Crapo JD, Fridovich I, Oury T, Folz RJ, Trova MP, Freeman BA;
CC PI Batinic-Haberle I, Day BJ;
XX
DR WPI; 2000-664150/64.
DR N-PSDB; AAA28294.
DR PC:NCBI; gi338284.
DR PC:SWISSPROT; P08294.
XX
CC PT New metal complexes of methine substituted porphines useful as catalytic
CC PT oxygen scavengers.
XX
CC PS Disclosure; Fig 24; 97pp; English.
XX
CC This invention relates to porphines and their metal complex oxidant
CC scavengers, where the metal is manganese, copper or iron. The porphines
CC exhibit cardiant; cerebroprotective; vasotropic; ophthalmological;
CC antiparkinsonian; nootropic; anticonvulsant; cytostatic; gynecological;
CC antiarteriosclerotic; antiinflammatory; antibacterial; immunosuppressive;
CC hypotensive; antidiabetic; antigout; antiasthmatic; and virucide
CC activity. The porphines act as superoxide dismutase (SOD) inhibitors and
CC are used as catalytic scavengers of reactive oxygen species to protect
CC against ischaemia reperfusion injuries associated with myocardial
CC infarction, stroke, acute head trauma, organ reperfusion following
CC transplantation, bowel ischaemia, pulmonary infarction, surgical
CC occlusion of blood flow, soft tissue injury, skeletal muscle reperfusion
CC injuries, glaucoma, macular degeneration of the eye, diseases of the
CC bones, to increase the limited storage viability of transplanted hearts,
CC kidneys, skin and other organs and tissues. The compounds are also useful
CC in the treatment of diseases of the central nervous system (including
CC AIDS dementia, stroke, amylotrophic lateral sclerosis), Parkinson's
CC disease, Huntington's disease, disease of the musculature, cardiac
CC fatigue of congestive heart failure, muscle weakness syndrome associated
CC with myopathies, neurological disorders, arthritis, systemic
CC hypertension, artherosclerosis, oedema, septic shock, pulmonary
CC hypertension, impotence, infertility, endometriosis, premature uterine
CC contractions, microbial infections, gout, Type II diabetes mellitus,
CC inflammation of the lungs, asthma, pneumonia, cystic fibrosis, chronic
CC sinusitis and autoimmune disease. The present sequence represents the
CC human EC-SOD protein. EC-SOD is a tetrameric glycosylated copper and zinc
CC containing enzyme. The enzyme is used to illustrate the activity of the
CC porphines of the invention
CC
CC Revised record issued on 15-JUN-2007 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 240 AA;
Query Match 100.0%; Score 1282; DB 1; Length 240;
Best Local Similarity 100.0%;
Matches 240; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MLALLCSCLLLAAGASDAWTGEDSAEPNSDSAEWIRDMYAKVTEIWQEVMQRRDDDGTLH 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MLALLCSCLLLAAGASDAWTGEDSAEPNSDSAEWIRDMYAKVTEIWQEVMQRRDDDGTLH 60
Qy 61 AACQVQPSATLDAAQPRVTGVVLFRQLAPRAKLDAFFALEGFPTEPNSSSRAIHVHQFGD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AACQVQPSATLDAAQPRVTGVVLFRQLAPRAKLDAFFALEGFPTEPNSSSRAIHVHQFGD 120
Qy 121 LSQGCESTGPHYNPLAVPHPQHPGDFGNFAVRDGSLWRYRAGLAASLAGPHSIVGRAVVV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LSQGCESTGPHYNPLAVPHPQHPGDFGNFAVRDGSLWRYRAGLAASLAGPHSIVGRAVVV 180
Qy 181 HAGEDDLGRGGNQASVENGNAGRRLACCVVGVCGPGLWERQAREHSERKKRRRESECKAA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 HAGEDDLGRGGNQASVENGNAGRRLACCVVGVCGPGLWERQAREHSERKKRRRESECKAA 240
However, none of Yu, Gan, Kim, Tokura or Crapo teach the polynucleotide encoding SOD3 includes the nucleotide sequence defined by SEQ ID NO: 2 or SEQ ID NO: 4 (as in claim 11).
Before the effective filing date of the claimed invention, Crapo (b) et al. taught a method of treating an inflammatory condition in a patient in need of such treatment comprising administering to the patient an effective amount of an oxidant scavenger, such as EC-SOD, under conditions such that the treatment is effected (Col. 4, lines 39-44). In fact, Crapo (b) teaches the polynucleotide encoding SOD3 includes the nucleotide sequence defined by SEQ ID NO: 2 as in claim 11. The alignment between SEQ ID NO: 2 (Qy, query) and the polynucleotide encoding SOD3 taught by Crapo (b) et al. (Db, database) is provided below.
RESULT 13
US-08-476-866-20
; Sequence 20, Application US/08476866
; Patent No. 5994339
; GENERAL INFORMATION:
; APPLICANT: CRAPO, JAMES D.
; APPLICANT: FRIDOVICH, IRWIN
; APPLICANT: OURY, TIM
; APPLICANT: DAY, BRIAN J.
; APPLICANT: FOLZ, RODNEY J.
; APPLICANT: FREEMAN, BRUCE A.
; TITLE OF INVENTION: SUPEROXIDE DISMUTASE AND MIMETICS THEREOF
; NUMBER OF SEQUENCES: 24
; CORRESPONDENCE ADDRESS:
; ADDRESSEE: NIXON & VANDERHYE P.C.
; STREET: 1100 NORTH GLEBE ROAD
; CITY: ARLINGTON
; STATE: VIRGINIA
; COUNTRY: U.S.A.
; ZIP: 22201-4714
; COMPUTER READABLE FORM:
; MEDIUM TYPE: Floppy disk
; COMPUTER: IBM PC compatible
; OPERATING SYSTEM: PC-DOS/MS-DOS
; SOFTWARE: PatentIn Release #1.0, Version #1.25
; CURRENT APPLICATION DATA:
; APPLICATION NUMBER: US/08/476,866
; FILING DATE:
; CLASSIFICATION: 424
; PRIOR APPLICATION DATA:
; APPLICATION NUMBER: US 08/322,766
; FILING DATE: 13-OCT-1994
; APPLICATION NUMBER: US 08/136,207
; FILING DATE: 15-OCT-1993
; CLASSIFICATION: 424
; ATTORNEY/AGENT INFORMATION:
; NAME: WILSON, MARY J.
; REGISTRATION NUMBER: 32,955
; REFERENCE/DOCKET NUMBER: 1579-74
; TELECOMMUNICATION INFORMATION:
; TELEPHONE: (703) 816-4000
; TELEFAX: (703) 816-4100
; TELEX: 200797 NIXN UR
; INFORMATION FOR SEQ ID NO: 20:
; SEQUENCE CHARACTERISTICS:
; LENGTH: 10079 base pairs
; TYPE: nucleic acid
; STRANDEDNESS: single
; TOPOLOGY: linear
; MOLECULE TYPE: DNA (genomic)
; FEATURE:
; NAME/KEY: CDS
; LOCATION: 5086..5803
US-08-476-866-20
Query Match 100.0%; Score 720; DB 5; Length 10079;
Best Local Similarity 100.0%;
Matches 720; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGCTGGCGCTACTGTGTTCCTGCCTGCTCCTGGCAGCCGGTGCCTCGGACGCCTGGACG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5085 ATGCTGGCGCTACTGTGTTCCTGCCTGCTCCTGGCAGCCGGTGCCTCGGACGCCTGGACG 5144
Qy 61 GGCGAGGACTCGGCGGAGCCCAACTCTGACTCGGCGGAGTGGATCCGAGACATGTACGCC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5145 GGCGAGGACTCGGCGGAGCCCAACTCTGACTCGGCGGAGTGGATCCGAGACATGTACGCC 5204
Qy 121 AAGGTCACGGAGATCTGGCAGGAGGTCATGCAGCGGCGGGACGACGACGGCACGCTCCAC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5205 AAGGTCACGGAGATCTGGCAGGAGGTCATGCAGCGGCGGGACGACGACGGCACGCTCCAC 5264
Qy 181 GCCGCCTGCCAGGTGCAGCCGTCGGCCACGCTGGACGCCGCGCAGCCCCGGGTGACCGGC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5265 GCCGCCTGCCAGGTGCAGCCGTCGGCCACGCTGGACGCCGCGCAGCCCCGGGTGACCGGC 5324
Qy 241 GTCGTCCTCTTCCGGCAGCTTGCGCCCCGCGCCAAGCTCGACGCCTTCTTCGCCCTGGAG 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5325 GTCGTCCTCTTCCGGCAGCTTGCGCCCCGCGCCAAGCTCGACGCCTTCTTCGCCCTGGAG 5384
Qy 301 GGCTTCCCGACCGAGCCGAACAGCTCCAGCCGCGCCATCCACGTGCACCAGTTCGGGGAC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5385 GGCTTCCCGACCGAGCCGAACAGCTCCAGCCGCGCCATCCACGTGCACCAGTTCGGGGAC 5444
Qy 361 CTGAGCCAGGGCTGCGAGTCCACCGGGCCCCACTACAACCCGCTGGCCGTGCCGCACCCG 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5445 CTGAGCCAGGGCTGCGAGTCCACCGGGCCCCACTACAACCCGCTGGCCGTGCCGCACCCG 5504
Qy 421 CAGCACCCGGGCGACTTCGGCAACTTCGCGGTCCGCGACGGCAGCCTCTGGAGGTACCGC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5505 CAGCACCCGGGCGACTTCGGCAACTTCGCGGTCCGCGACGGCAGCCTCTGGAGGTACCGC 5564
Qy 481 GCCGGCCTGGCCGCCTCGCTCGCGGGCCCGCACTCCATCGTGGGCCGGGCCGTGGTCGTC 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5565 GCCGGCCTGGCCGCCTCGCTCGCGGGCCCGCACTCCATCGTGGGCCGGGCCGTGGTCGTC 5624
Qy 541 CACGCTGGCGAGGACGACCTGGGCCGCGGCGGCAACCAGGCCAGCGTGGAGAACGGGAAC 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5625 CACGCTGGCGAGGACGACCTGGGCCGCGGCGGCAACCAGGCCAGCGTGGAGAACGGGAAC 5684
Qy 601 GCGGGCCGGCGGCTGGCCTGCTGCGTGGTGGGCGTGTGCGGGCCCGGGCTCTGGGAGCGC 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5685 GCGGGCCGGCGGCTGGCCTGCTGCGTGGTGGGCGTGTGCGGGCCCGGGCTCTGGGAGCGC 5744
Qy 661 CAGGCGCGGGAGCACTCAGAGCGCAAGAAGCGGCGGCGCGAGAGCGAGTGCAAGGCCGCC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5745 CAGGCGCGGGAGCACTCAGAGCGCAAGAAGCGGCGGCGCGAGAGCGAGTGCAAGGCCGCC 5804
The combination of prior art cited above in all rejections under 35 U.S.C.103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1,148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A and G are applicable. Before the effective filing date of the claimed invention, it would have been prima facie obvious to an artisan of ordinary skill to combine the teachings of Yu et al., wherein Yu teaches the over-expression of SOD3 in the synovial tissue of a subject having inflammatory arthritis, wherein said inflammatory arthritis is characterized by oxidative stress within the inflamed joint, with the teachings of Gan et al., wherein Gan teaches pairing mesenchymal stem cells, which have inherent anti-oxidative stress properties, and a polynucleotide encoding SOD3 resulted in a therapeutic additive effect in a subject in need thereof, with a reasonable expectation of success. That is, one of ordinary skill in the art would have found it prima facie obvious to transfect mesenchymal stem cells with a polynucleotide encoding SOD3 such that SOD3 is overexpressed in an inflammatory disease characterized by an increase in oxidative stress with a reasonable expectation of arriving at the claimed invention. One of skill in the art would have been sufficiently motivated to make such a modification because Yu already found success in treating an inflammatory disease with over-expression of SOD3 and Gan adds that mesenchymal stem cells inherently possess anti-oxidative stress properties. It should be noted that the courts held in In re Kerkhoven, 205 USPQ 1069 (C.C.P.A. 1980) held that "it is prima facie obvious to combine two compositions each of which is taught by prior art to be useful for same purpose in order to form third composition that is to be used for very same purpose;" wherein the "idea of combining them flows logically from their having been individually taught in prior art." In this regard the combination of Yu et al. and Gan et al. are all directed to compositions that reduce oxidative stress, thus the combination would have been prima facie obvious.
Moreover, the skilled artisan would have found it prima facie obvious to administer the SOD3 transfected mesenchymal stem cells of Yu in view of Gan to a subject suffering from an inflammatory skin disease such as psoriasis because Kim observed that EC-SOD expression in tissue from psoriasis patients was markedly decreased in psoriatic lesional and nonlesional skins from psoriasis patients in comparison to normal skin from healthy volunteers and that EC-SOD exhibited antiangiogenic and anti-inflammatory effects, two key markers of psoriasis.
Lastly, in the method of treating inflammation as set forth by the teachings of Yu et al., Gan et al. and Kim et al., the skilled artisan would have been sufficiently motivated to use the SOD3 amino acid sequence of Crapo or the polynucleotide encoding SOD3 of Crapo (b) because Crapo teaches both the amino acid sequence and the polynucleotide are suitable for treating inflammatory diseases.
Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
Therefore, the claimed invention, as a whole, was clearly prima facie obvious.
Double Patenting
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.
Claim 13 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11730766. Although the claims at issue are not identical, they are not patentably distinct from each other because of the following:
Instant claim 13 is drawn to a method for treating an inflammatory disease, the method being characterized by administering an effective amount of a pharmaceutical composition to a subject in need thereof, the pharmaceutical composition comprising, as an overexpressing SOD3.
Claim 1 of U.S. Patent ‘766 is drawn to a method for treating an inflammatory skin disease in a subject, the method comprising administering an effective amount of a composition comprising, as an active ingredient, mesenchymal stem cells overexpressing extracellular superoxide dismutase (SOD3) to the subject in need thereof, wherein the inflammatory skin disease is one or more disease selected from the group consisting of psoriasis and atopic dermatitis.
It is clear that all the elements of the application claims are to be found in patent claims (as the application claims fully encompasses patent claims). The difference between the application claims and the patent claims lies in the fact that the patent claim includes many more elements and is thus much more specific. Thus the invention of claims of the patent is in effect a “species” of the “generic” invention of the application claims. For example, patent claims require mesenchymal stem cells to overexpress SOD3; whereas, instant application requires SOD3 overexpression. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993). Since application claims is anticipated by claims of the patent, it is not patentably distinct from claims of the patent.
Authorization to Initiate Electronic Communications
The examiner may not initiate communications via electronic mail unless and until applicants authorize such communications in writing within the official record of the patent application. See M.P.E.P. § 502.03, part II. If not already provided, Applicants may wish to consider supplying such written authorization in response to this Office action, as negotiations toward allowability are more easily conducted via e-mail than by facsimile transmission (the PTO's default electronic-communication method). A sample authorization is available at § 502.03, part II.
Conclusion
No claim is allowed.
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/TITILAYO MOLOYE/ Primary Examiner, Art Unit 1632