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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) was filed before the mailing date of the non-final first action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlinks and/or other form of browser-executable code on pages1-lines 26,31, 33; and page 3 -lines 5,9,16, 21 . Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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 8 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 8, the claim recites the term “ repetitively”. The term is unclear because it is uncertain whether “ expressed repetitively” requires continuous expression, repeated expression, inducible expression, or another defined pattern of expression. The specification does not provide a sufficiently definite standard by which one of ordinary skill in the art could determine whether Decorin expression satisfies the limitation. Accordingly, the metes and bounds of claim 8 are unclear.
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 1,4,5,9-13, and 16 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Braid et al (US 2019/0134101 A1).
Regarding claim 1, Braid et al disclose a genetically modified human umbilical cord perivascular cells (“HUVPVCs”) genetically modified to express a wound healing agent selected form a non-antibody anti-fibrotic factor. Braid et al further disclose that the antifibrotic factor may be a TGFB antagonist and expressly identified Decorin as such a TGFB antagonist. Braid et al further disclose that the HUCPVC synthesizes and secrets the wound healing agent. ([0005-0007]). Braid et al additionally disclose genetic modification of the HUCPVCs by viral transduction and expressly states that the retroviral transduction may be lentiviral transduction. ([0012] and [0125]). Braid et al also disclose a pharmaceutical composition comprising the genetically modified mesenchymal cell (i.e. HUCPVCs) and pharmaceutically acceptable carriers or excipient. In particular, Braid et al disclose a pharmaceutical composition comprising genetically modified HUCPVCs, and its disclosure specifically identifies Decorin as the non-antibody TGFB antagonist. ( See claims 1-3, and 29). It is noted that the preamble of claim 1 recites “ for use in the treatment of fibrosis of lung or kidney”. Such recitation is considered to be an intended use and not an actual limitation of the claimed invention. As it has been held that when the body of a claim fully and intrinsically sets forth all limitations of the claimed invention, and the preamble merely states the intended use of the invention, rather than any distinct definition of the any of the claimed invention’s limitations, the preamble is not considered a limitation and is of no significance to claim construction. See MPEP § 2111.02. To be applicable the prior art product must only be shown to be suitable for the intended use, but disclosure of use of the prior art product in said intended use is not necessary. In the instant case, Braid et al defines “ fibrosis” broadly to include disorders involving abnormal deposition of scar tissue and expressly state that fibrosis may occur in various organs, including kidney and lung. [0083]. Braid et al also expressly characterize Decorin as an anti-fibrotic factor. Therefore, under the broadest reasonable interpretation , the recitation of treatment of lung or kidney fibrosis does not distinguish the claimed modified cells from the modified HUCPVC disclosed by Braid et al because the recitation identifies an intended use of the claimed cell rather than a structural limitation distinguishing the cell from Braid’s cell. Accordingly, Braid et al anticipate instant claim.
Regarding claim 4, Braid et al expressly disclose human HUCPVCs. HUCPVCs are mesenchymal/perivascular cells, and Braid identifies them as a mesenchymal stem-cell population. [0106]. Braid therefore discloses the claimed mesenchymal cells of human origin.
Regarding claim 5, Braid et al expressly disclose that the genetically modified HUCPVCs may be allogenic to the subject. [0108].
Regarding claim 9, Braid et al expressly disclose viral transduction of HUCPVCs, including retroviral transduction, and further expressly identifies lentiviral transduction as a type of retroviral transduction. [0132].
Regarding claims 10-11, Braid et al disclose pharmaceutical compositions comprising genetically modified HUCPVs. Braid et al further disclose that the genetically modified HUCPVs express Decorin as anti-fibrotic factor and expressly discloses retroviral modification. It should be noted that the additional recitations directed to preventing or slowing fibrosis of the kidney (claim 10) or lung (claim 11) are directed to intended use rather than a structural limitation of the medicament . According to the MPEP, the prior art product must only be shown to be suitable for the intended use, but disclosure of use of the prior art product in said intended use is not necessary. In the instant case, Braid et al identifies kidney and lung among organs which fibrosis may occur and identifies Decorin as an anti-fibrotic factor. [0083]. Accordingly, Braid et al anticipate instant claims.
Regarding claims 12-13, and 16, Braid et al disclose a method of genetically modifying HUCPVs to express a wound healing agent, including Decorin. Braid further disclose introducing the genetic material by viral transduction and specifically disclose retroviral and lentiviral transduction. ( See claims 3, 10-11, 12-13).
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claims 2-3, and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Braid et al (US 2019/0134101 A1), in view of Krusius and Ruoslathi (PNAS, 1986).
The teachings of Braid et al are set forth above. Braid et al anticipate claims 1,4,5,9-13, and 16.
Regarding claims 2-3, and 14-15, following the discussion above, Braid et al disclose a genetically modified human mesenchymal cells expressing human Decorin. Specifically, Braid et al teach recombinant adenovirus pAd5-Dcn encoding the full length human Decorin gene and use of the resulting genetically modified cells to express and secret human Decorin. [0202]. Thus, Braid et al teach a genetically modified mesenchymal cells comprising an expression construct encoding the full length human Decorin. However, Braid et al do not provide a DCN accession number, or a sequence identifying the exact isoform of Decorin being used.
Krusius and Ruoslathi et al disclose PG40, that is subsequently identified as Decorin, and provide the nucleotide sequence and the encoded amino acid sequence corresponding to human PG40/Decorin. ( See Fig.2). It should be noted that the sequence disclosed by Krusius and Ruoslathi corresponds to Decorin isoform A. Thus, Krusius and Ruoslathi establish the sequence identity and structure of the known human Decorin protein. Therefore, it would have been prima facie obvious at the time the invention was filed to modify the teachings of Braid et al and select the conventional full length (i.e. isoform A) taught by Krusius and Ruoslathi to generate genetically modified cells expressing Decorin isoform A. Because Braid et al teach a genetically modified mesenchymal cells expressing the full length human Decorin but fail to specify the corresponding isoform. Krusius and Ruoslathi provide the known sequence information of human Decorin isoform A. Thus, an ordinary skill in the art would have had a reasonable expectation of success when modifying the cells of Braid et al to express the Decorin isoform A, taught by Krusius and Ruoslathi , would have the predictable results of expressing a functional human Decorin. In other words, instant claims are examples of combining prior art elements according to known methods to yield predictable results. See MPEP 2143 (I)(A).
Claims 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Braid et al (US 2019/0134101 A1), in view of Ikeyama et al ( US 20190117701 A1)
The teachings of Braid et al are set forth above. Braid et al anticipate claims 1,4,5,9-13, and 16.
Regarding claims 6-7, following the discussion of claim 1 above Braid et al disclose genetically modified human mesenchymal cells comprising recombinant construct encoding the full length human Decorin. In particular, Braid et al teach a mesenchymal stem cell derived from human umbilical cord perivascular cells (HUCPVCs). However, Braid et al do not teach the utilization of MSCs derived from endometrial tissue. Ikeyama et al teach supplement Braid et al by teaching that mesenchymal stem cells maybe obtained from multiple tissue sources, including adipose tissue, bone marrow, or from endometrial tissue, and further describe mesenchymal stem cells in the context of Decorin-related biological activity. ( [0063], [0093], and claims 1-2,4,5). Therefore, it would have been prima facie obvious to one with ordinary skill in the art at the time the invention was filed to employ the mesenchymal cells obtained from a known source such as endometrial tissue in the Decorin expression cell system of Briad et al. The modification merely represent the selection of a known mesenchymal stem cell source in a known-Decorin-expression system.
Claims 17 is rejected under 35 U.S.C. 103 as being unpatentable over Braid et al (US 2019/0134101 A1), in view of Montespan et al ( Journal of Immunology Research, 2014).
The teachings of Braid et al are set forth above. Braid et al anticipate claims 1,4,5,9-13, and 16.
Regarding claim 17, following the discussion of claim 1 above, Braid et al teach the production of genetically modified mesenchymal stem cells expressing the full length human Decorin using a viral vector, wherein the mesenchymal cells derived from human umbilical cord perivascular cells (HUCPVCs). However, Briad et al do not teach the limitation wherein the mesenchymal stem cells express an HLA-G molecule. Montespan et al supplement Braid et al by teaching that MSCs derived from bone marrow and adipose tissue display immunomodulatory properties through expression of soluble factors including HLA-G, and that HLA-G expression is maintained after osteodifferentiation. Montespan et al further explains that HLA-G expressed by MSCs contributes to their immunosuppressive properties. ( See abstract). Therefore, it would have been obvious to employ an HLA-G expressing mesenchymal stem cell in the Decorin-expression system of Braid et al to obtain the known immunomodulatory properties associated with HLA-G. An ordinary skill in the art would have had a reasonable expectation of success because both Decorin expression and HLA-G expression were independently demonstrated in mesenchymal cells.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FATIMAH KHALAF MATALKAH whose telephone number is (703)756-5652. The examiner can normally be reached Monday-Friday,7:30 am-4:30 pm 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, Tracy Vivlemore can be reached on 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/FATIMAH KHALAF MATALKAH/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
Prosecution Insights