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 .
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 9 and 18 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.
The claims recite “STP705”, which is not a term of the art and does not sufficiently define the compound and therefore the metes and bounds of the compound cannot be clearly ascertained by the claim language and the claims are not definite.
From a review of the specification, it appears that STP705 requires SEQ ID NOs: 1-4, which should be recited in the claim.
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 1-8, 10-17, 19, and 20 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 is directed to delivery of any siRNA that binds to an mRNA that codes for any TGF-β1 and any siRNA that binds to an mRNA that codes for any Cox2 or any PTGS2.
The specification discloses siRNAs wherein one strand is fully complementary to a specific TGF-β1 target sequence or to a specific Cox2 target sequence. The species of the specification are not representative of the entire claimed genus of siRNAs that bind on any level (i.e. 2 nt) to any portion of any mRNA that codes for any TGF-β1 and any siRNA that binds at any level to any portion of any mRNA that codes for any Cox2 or any PTGS2.
The specification does not adequately describe the structure required for the recited function. The specification does not disclose any other siRNAs targeted to any other TGF-β1 or Cox2 target sequences or that bind at varying levels to the target sequences. The specification does not even disclose a single species of siRNA that binds at any level to any possible PTGS2 sequence. Without knowledge of the specific target sequences and knowledge of the specific structure required between the siRNA and the target, one would not be able to readily envision which siRNAs are necessarily included or excluded from the recited genus and one would not be able to readily recognize which siRNAs have the structure required for the recited function.
With regards to instant claim 11, the claim is directed to a method of treating a patient with “RNAi therapy” via delivery of one or more double stranded nucleic acids capable of inhibiting the activity of any TGF-β1, wherein the second target gene is any Cox2 or any PTGS2. The specification does not define or adequately describe what is required for “RNAi therapy”. RNAi agents are normally long dsRNA, shRNAs, or siRNAs, but instant claim 13 includes miRNAs. The specification does not adequately describe which miRNAs would function via RNAi.
Additionally, the specification does not adequately describe the structure required for the function for any double stranded nucleic acid molecule of any length that acts via any mechanism to have the function of being capable of inhibiting the activity of any TGF-β1, any Cox2, or any PTGS2. The TGF-β1 or Cox2 siRNAs of the specification are not representative of any possible double stranded molecule that is capable of inhibiting the activity of any TGF-β1, any Cox2, or any PTGS2. The specification does not describe even a single species of double stranded nucleic acid molecule of any length that acts via any mechanism and has the function of being capable of inhibiting the activity of any PTGS2; and does not describe even a single species of miRNAs or shRNAs that have the structure for the required function. One would not be able to readily recognize which miRNAs, shRNAs, or siRNAs would have the structure to function as claimed.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The claims are rejected under the written description requirement for failing to disclose adequate species to represent the claimed genus, the genus being double stranded RNAi agents of any length that comprise 15 contiguous nucleotides of instant SEQ ID NO: 669 in the antisense strand in the same or a different portion than the double-stranded region and have no other sequence specificity to any specific HAO1 target sequence and function by inhibiting the expression of HAO1.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing.
To achieve the desired function, it appears that the structure is required to be of a shorter length than the claimed genus which has no length limitation. With respect to siRNAs, a single species double stranded nucleic acids, Elbashir et al. (The EMBO Journal, Vol. 20, No. 23, pages 6877-6888, 2001) teaches that duplexes of 21-23 nt RNAs are the sequence specific mediators of RNAi and that even single mismatches between the siRNA duplex and the target mRNA abolish interference (abstract and page 6888).
The claims encompass very long dsRNA, for example, that can trigger RNAi. Such dsRNA with 15 contiguous nucleotides of SEQ ID NO: 669 would not likely function as claimed. For example, Parrish et al. (Molecular Cell, Vol. 6, 1077–1087, November, 2000) teach that sequences of 1000 bp trigger RNAi (page 1078). Without further description of the structure required for the function, one would not be able to readily recognize which dsRNA molecules are capable of achieving the recited function.
With regards to miRNAs, the specification does not adequately describe the genus of miRNAs that would function as claimed. Broughton et al. (Molecular Cell, 64, 320–333, 2016) teach that through the analysis of thousands of sequences, pairing to the miRNA seed emerged as the predominant motif associated with functional interactions. Broughton et al. teach that they discovered that additional pairing to 3’ sequences is prevalent in the majority of target sites and leads to specific targeting by members of miRNA families. By editing an endogenous target site, we demonstrate that 3’ pairing determines targeting by specific miRNA family members and that seed pairing is not always sufficient for functional target interactions. Overall, our analysis revealed that sequences in the 5’ as well as the 3’ regions of a miRNA provide the information necessary for stable and specific miRNA-target interactions in vivo (Summary, page 320). Without knowledge of the specific structure required for the miRNA, one would not be able to recognize which miRNAs have the required structure to function as claimed to inhibit the recited targets and remodel adipose tissue.
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of agents within the instant enormous genus that function as claimed. Thus, one skilled in the art would be led to conclude that Applicant was not in possession of the claimed invention at the time the application was filed.
Claims 1-20 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 a method of inhibiting TGF-β1 with the TGF-β1 siRNAs of the specification or Cox2 with the Cox2 siRNAs of the specification, does not reasonably provide enablement for a method of remodeling any type of adipose tissue via any mode of delivery of any siRNA that binds at any level to any TGF-β1, and of any siRNA that binds at any level to any Cox2 or PTGS2; or delivery of any possible double stranded nucleic acid that is capable of inhibiting the activity of the recited genes. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Factors to be considered in a determination of lack of enablement 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.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)
The claims are directed to a method of remodeling any type of adipose tissue via any mode of delivery of any siRNA that binds at any level to any TGF-β1, and of any siRNA that binds at any level to any Cox2 or PTGS2; or delivery of any possible double stranded nucleic acid that is capable of inhibiting the activity of the recited genes.
The specification demonstrates delivery of STP705 directly into squamous cell carcinoma tumors at the highest dose (120 µg) exhibited skin changes consistent with panniculitis, an inflammation of subcutaneous adipose tissue. STP705 is a specific nanoparticle formulation comprising a specific siRNA targeted to TGF-β1 and a specific siRNA targeted to Cox2 (page 25).
Direct intratumoral delivery of STP705 at a specific concentration with a result of skin changes consistent with panniculitis, an inflammation of subcutaneous adipose tissue is not enabling for a method of remodeling any type of adipose tissue via any mode of delivery in any possible patient of any siRNA that binds at any level to any TGF-β1, and of any siRNA that binds at any level to any Cox2 or PTGS2; or delivery of any possible double stranded nucleic acid that is capable of inhibiting the activity of the recited genes.
The specification does not disclose or enable any other siRNAs targeted to any other TGF-β1 or Cox2 target sequences or that bind at varying levels to the target sequences that function by remodeling any possible adipose tissue in any patient. The specification does not even disclose a single species of siRNA that binds at any level to any possible PTGS2 sequence. Without knowledge of the specific target sequences and knowledge of the specific structure required between the siRNA and the target, one would not be able to readily determine which siRNAs via any mode of delivery and at any concentration would result in remodeling of any type of adipose tissue.
With regards to miRNAs, the specification does not enable delivery of any miRNA that functions via RNAi of the instantly recited targets and results in remodeling of any possible adipose tissue. It would involve undue experimentation to determine which miRNAs would predictably function as claimed.
The specification does not disclose even a single species of double stranded nucleic acid molecule of any length that acts via any mechanism and has the function of being capable of inhibiting the activity of any PTGS2; and does not disclose even a single species of miRNAs or shRNAs that have the structure for the required function. One would not be able to readily determine which miRNAs, shRNAs, or siRNAs would predictably result in remodeling of any possible type of adipose tissue at any concentration in any possible patient.
Additionally, there is no guidance in the specification as filed that teaches how to deliver the instantly recited genus of agents, each having different delivery challenges, and predictably remodel adipose tissue in vivo.
With regards to siRNAs, a single species of the instant inhibitors, the instant siRNAs are not required to have any specific structural relationship with any specific target sequence. It is known in the siRNA field that not any siRNA to any target sequence will result in inhibitory effect. Even from those that are inhibitory to the instantly recited targets, not all of this pool would predictably result in treatment effects in vivo.
Although applicant has demonstrated RNA interference in vitro via specific siRNAs, applicant is not enabled for mediating RNA interference in vivo by the broadly recited methods, as delivery and effective action therein is known in the art to be unpredictable with regards to dsRNA duplexes. Activity in vitro is not predictable of the in vivo therapeutic effect in the in vivo complex environment.
For example, Elbashir et al. (The EMBO Journal, Vol. 20, No. 23, pages 6877-6888, 2001) teaches that duplexes of 21-23 nt RNAs are the sequence specific mediators of RNAi and that even single mismatches between the siRNA duplex and the target mRNA abolish interference (abstract and page 6888).
Fujita et al. (Int. J. Mol. Sci. 2015, 16, 5254-5270) teach that two types of small RNA molecules, small interfering RNAs (siRNAs) and microRNAs (miRNAs), have a central function in RNAi technology. The success of RNAi-based therapeutic delivery may be dependent upon uncovering a delivery route, sophisticated delivery carriers, and nucleic acid modifications (page 5254). Fujita et al. teach that the success of an RNAi-based therapy in clinical trials rests on careful selection of target genes and miRNAs. Moreover, we suggest that a delivery route, sophisticated delivery carriers, chemical modification, and modified RNAi platforms are needed to enhance RNAi effects in cancer cells (pages 5262-5263).
Friedrich et al. (BioDrugs (2022) 36:549–571) teach that still, the development of siRNA therapeutics faces several challenges and issues, including the definition of optimal siRNAs in terms of target, sequence, and chemical modifications, siRNA delivery to its intended site of action, and the absence of unspecific off-target effects (Abstract). Friedrich et al. teach that the use of short siRNA is preferred because longer siRNAs can provoke an inflammatory antiviral immune response (page 551).
Friedrich et al. teach: As a basic parameter, the GC content of an siRNA is addressed by algorithms and its range should be between ~30 and 60%. Too low GC content can lead to weak or unspecific binding, whereas too high GC content may impede unwinding by helicase and incorporation in the RISC complex. Between nucleotides 9 and 14, however, low GC content is important to increase RISC function during mRNA cleavage. Sequences that could lead to secondary structures in the sense or antisense stand must be avoided (e.g., internal repeats, palindromes, CCC or GGG sequences). A proper duplex formation is essential for functional siRNA. Additionally, sequences that contain single nucleotide polymorphisms, miRNA seed matches, and known toxic motifs must be avoided (page 552).
Friedrich et al. teach: The 5′-untranslated region (and 3′-untranslated region) of mRNA as well as sequences close to the start codon are not recommended as siRNA targets, as the binding of regulatory proteins in this area may impede RISC binding and thus the silencing effect. Rather, selecting regions in the open reading frame about 50–100 nucleotides downstream of the start codon is recommended. Furthermore, siRNAs closer to the start codon seem to be more efficient than those further downstream (page 552). Friedrich et al. is evidence as to the delivery challenges, as well as the fact that not any siRNA inhibitor of a target would result in the desired therapeutic effect.
As outlined above, it is well known that there is a high level of unpredictability in the RNAi art (a single species of the instant inhibitors) for therapeutic in vivo applications and design. The scope of the claims in view of the specification as filed together do not reconcile the unpredictability in the art to enable one of skill in the art to make and/or use the claimed invention, namely a broad method of remodeling any possible adipose tissue via broad systemic delivery of a broad genus of agents that act via different mechanisms and have different levels of activity encompassing in vivo effects.
MPEP 2164.01
Any analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.
Also, MPEP 2164.01(a)
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Given the teachings of the specification as discussed above, one skilled in the art could not predict a priori whether introduction of any possible agent of the instant genus in vivo by the broadly disclosed methodologies of the instantly claimed invention, would result in successful remodeling of any type of adipose tissue. To practice the claimed invention, one of skill in the art would have to de novo determine; the stability of the molecule in vivo, delivery of the molecule to the whole organism, specificity to the target tissue in vivo, dosage and toxicity in vivo, and entry of the molecule into the cell in vivo and the effective action therein. Without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation (see MPEP 2164.01(a)).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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) 1-3, 5-8, 10-17, 19, and 20 is/are rejected under 35 U.S.C. 102(a)(1) or (a)(2) as being anticipated by He et al. (US 2012/0115923 A1).
He et al. teach compositions and methods using siRNA to target various genes expressed in cells of injured tissue during scar formation to promote scar-free wound healing (abstract).
He et al. teach: [0014] The composition used for contacting injured tissues or cells may comprise a plurality of targeting polynucleotides of the invention and the polynucleotides may target a plurality of gene sequences. The composition may further comprise a TargeTran nanoparticle solution. The targeting polynucleotides found in the composition may target sequences of genes such as Cox-2 and TGF-β, found in tables 1-7. The targeting polynucleotides may comprise one or more siRNA duplexes against one or more gene sequences, such as Cox-2/ TGF-β1/IL-8, Cox-2/ TGF-β1/IL-6, Cox-2/ TGF-β1/fibronectin, Cox-2/ TGF-β1/smad3 and other combinations of three or more gene sequences. The polynucleotides of the invention may be mixed in equal or different ratios (instant claims 1, 11, and 13).
He et al. teaches a pharmaceutical composition comprising the nanoparticle formulation comprising the siRNAs and a pharmaceutically acceptable carrier [0045] (instant claims 1 and 11).
He et al. teach incorporation of carriers including cationic copolypeptides such as histidine-lysine (HK) ([0051] and claims) (instant claims 2, 3, and 12). He et al. teaches that the siRNA can be conjugated (RGD-PEG-PEI)([0051]) (instant claim 14).
He et al. teach: [0046] A pharmaceutical composition of the invention is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral, nasal, inhalation, transdermal (topical), transmucosal, and rectal administration (instant claims 5 and 6).
He et al. teach: [0021] Efficient silencing is generally observed with siRNA duplexes composed of a 16-30 nt sense strand and a 16-30 nt antisense strand of the same length (instant claims 7, 8, 15, 16, 19, and 20).
He et al. teach: [0013] This invention also provides a method of suppressing scar formation during the cutaneous wound healing process by contacting the injured tissues or cells, at a time of a surgery, wound treatment, injury recovery or skin grafting, with a composition comprising a targeting polynucleotide of the invention. In one embodiment, the composition is applied topically. In another embodiment, the composition is locally injected (instant claim 11).
Since He et al. teaches a method comprising each of the instant method steps, the method would necessarily achieve the recited outcome of remodeling adipose tissue, absent evidence to the contrary (instant claims 1, 10, 11, and 17). As stated in the MPEP (see MPEP 2112), something that is old does not become patentable upon the discovery of a new property. The only recited method step is delivering of the siRNAs.
Therefore, the instant invention is anticipated by He et al.
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 (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
Claim(s) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over He et al. (US 2012/0115923 A1), as set forth above, further in view of Leng et al. (Molecular Therapy, vol. 20, no. 12, 2012, 2282-2290), and Lu et al. (US 2010/0319074 A1).
He et al. teach compositions and methods using siRNA to target various genes expressed in cells of injured tissue during scar formation to promote scar-free wound healing (abstract).
He et al. teach: [0014] The composition used for contacting injured tissues or cells may comprise a plurality of targeting polynucleotides of the invention and the polynucleotides may target a plurality of gene sequences. The composition may further comprise a TargeTran nanoparticle solution. The targeting polynucleotides found in the composition may target sequences of genes such as Cox-2 and TGF-β, found in tables 1-7. The targeting polynucleotides may comprise one or more siRNA duplexes against one or more gene sequences, such as Cox-2/ TGF-β1/IL-8, Cox-2/ TGF-β1/IL-6, Cox-2/ TGF-β1/fibronectin, Cox-2/ TGF-β1/smad3 and other combinations of three or more gene sequences. The polynucleotides of the invention may be mixed in equal or different ratios (instant claims 1, 11, and 13).
He et al. teaches a pharmaceutical composition comprising the nanoparticle formulation comprising the siRNAs and a pharmaceutically acceptable carrier [0045] (instant claims 1 and 11).
He et al. teach incorporation of carriers including cationic copolypeptides such as histidine-lysine (HK) ([0051] and claims) (instant claims 2, 3, and 12). He et al. teaches that the siRNA can be conjugated (RGD-PEG-PEI)([0051]) (instant claim 14).
He et al. teach: [0046] A pharmaceutical composition of the invention is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral, nasal, inhalation, transdermal (topical), transmucosal, and rectal administration (instant claims 5 and 6).
He et al. teach: [0021] Efficient silencing is generally observed with siRNA duplexes composed of a 16-30 nt sense strand and a 16-30 nt antisense strand of the same length (instant claims 7, 8, 15, 16, 19, and 20).
He et al. teach: [0013] This invention also provides a method of suppressing scar formation during the cutaneous wound healing process by contacting the injured tissues or cells, at a time of a surgery, wound treatment, injury recovery or skin grafting, with a composition comprising a targeting polynucleotide of the invention. In one embodiment, the composition is applied topically. In another embodiment, the composition is locally injected (instant claim 11).
Since He et al. teaches a method comprising each of the instant method steps, the method would necessarily achieve the recited outcome of remodeling adipose tissue, absent evidence to the contrary (instant claims 1, 10, 11, and 17). As stated in the MPEP (see MPEP 2112), something that is old does not become patentable upon the discovery of a new property. The only recited method step is delivering of the siRNAs.
He et al. does not teach that the copolymer is H3K4b (instant claim 4).
However, it would have been obvious for the copolymer to be H3K4b because Leng et al. teach that H3K4b siRNA carriers have greater pH buffering capacity comparted with other HK peptides and that there carriers minimize toxicity (abstract). One would reasonably expect the benefits taught by Leng et al. when incorporated into the formulation of He et al.
He et al. does not teach the specific siRNA sequences of STP705 (instant SEQ ID NOs: 1-4) as the Cox-2 and TGF-β siRNAs (instant claims 9 and 18).
However, it would have been obvious to select these sequences as a matter of design choice because they were known Cox-2 and TGF-β1 siRNAs, both taught by Lu et al. for healing and skin conditions (see the 5th 25-mer sense sequence for Cox-2, page 15; and see the 1st sense sequence for TGF-β1, page 14).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached M-F 8:00am-6:00pm.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636