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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/05/2025 has been entered.
Status of the application
Receipt of applicant’s remarks and claim amendments filed on 08/05/2025 are acknowledged.
However, applicants’ arguments for the previous 103 rejection are found not persuasive. Accordingly, the previous rejection is maintained and modified to address amended claims. Please see the examiners response to applicants below.
Response to Arguments
Applicants main argument is that the rejection of the pending claims fails on at least “a finding that the prior art included each element claimed, although not necessarily in a single prior art reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference”; because:
* Byrne, either alone or in combination with the other references fails to teach, suggest or disclose a star polypeptide with peptide arms that are 20 amino acids long or less; and
* Byrne, either alone or in combination with the other references fails to teach, suggest or disclose a ratio of nitrogen in the star polypeptide to phosphates in the mRNA ("the N/P ratio") that is 20 or lower.
For at least these reasons, the rejection of the pending claims should be withdrawn.
In fact, Byrne teaches G5(64)-PLL5, wherein “5” indicates 5 L-lysine subunits per PLL arm.
Byrne also teaches N/P ratios for their star peptides, see Fig.1-13, wherein the ratio ranges from 1-100, which overlaps claimed range.
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 of this title, 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, 4, 7-8, 10-12, 14-15, 18 and 20-26 are rejected under 35 U.S.C. 103 as being unpatentable over Byrne (Biomater. Sci., 2013, 1, 1223-1234; see applicants filed IDS dated ) in view of Sanchez-Gonzales (International Journal of Peptides, 22-Feb 2012, 1-10), Vorland (Scandinavian Journal of Infectious Diseases, vol.31, issue 5, 1999).
For claims 1, 4, 7 and 26:
Byrne teaches the following:
Star-shaped polypeptides are an attractive class of molecules for use as gene delivery vectors owing to their potential improved biocompatibility, structural characteristics and therapeutic “cargo” capacity. All star-shaped polypeptides efficiently packaged pDNA into discrete spherically shaped and positively charged nanocomplexes at low N/P ratios with sizes as low as <100 nm whereas the equivalent linear polypeptide required a higher complexation ratio. The complexation of siRNA with star-shaped PLL (poly-L-Lysine) was greatly superior to linear PLL. In particular the small armed, less densely branched star polypeptides were most promising as both pDNA and siRNA delivery vectors owing to their optimum sizing and complexation data. All star polypeptides offered similar protection of pDNA and siRNA from nuclease degradation once complexed. Overall the promising nucleic acid complexation, sizing, morphology and protection capacity of two different genetic “cargoes” highlight the potential of polypeptide dendrimer hybrids as gene delivery vectors.
Based on the above, Byrne developed and exemplified a method of pDNA transfection of Calu-3 cells using linear and star-shaped G5(64)-PLL40 polyplexes [see page 1226]. So, the “transfection of Calu-3 cells” is interpreted as “a method of stimulating a response” by administering star-shaped polypeptide.
In the above, G5(64)-PLL40 is identical to applicants elected species.
In addition, Byrne teaches G5(64)-PLL5, wherein “5” indicates 5 L-lysine subunits per PLL arm.
Byrne also teaches N/P ratios for their star peptides, see Fig.1-13, wherein the ratio ranges from 1-100, which overlaps claimed range.
The meaning of ‘stimulating a response’ in a subject can be interpreted as “cell(s) accepts or binds to the star-shaped polypeptide or its conjugate” or “star-shaped polypeptide stimulates cell and gets a response from the cell and so that it binds to cell or it penetrate into cell”.
Byrne also exemplified polypeptide/siRNA polyplexes and described their preparative methods for various sizes [see section “Particle size, surface charge and morphology of siRNA-PLL polyplexes” in pages 1227-1230].
The difference is that Byrne is silent on exemplifying applicants method of stimulating a response in a subject with applicants elected species, which are G5(64)-PLL5 and nucleic acid as a mRNA.
However, based on the guidance and teachings of Byrne, it appears that the criticality is in the star-shaped polypeptide, not whether the vector is siRNA or mRNA or DNA, and so, these are equivalents. Though Byrne is silent on exemplifying their teachings with mRNA, but it does not mean that their methodology does not work with mRNA. Moreover, the size of mRNA falls with in the range of siRNA to DNA. Therefore, a skilled person in the art would be motivated to extrapolate the teachings of Byrne to mRNA and reach applicants method with a reasonable expectation of success.
Established case law states that the mere substitution of an equivalent (something equal in value or meaning, as taught by analogous prior art) is not an act of invention; where equivalency is known to the prior art, the substitution of one equivalent for another is not patentable. See In re Ruff 118 USPQ 343 (CCPA 1958). In this case, siRNA, mRNA and DNA are interchangeable or equivalents.
For claim 8:
In the teachings of Byrne) does not recite any additional therapeutic active agents as an additional component in their method.
For claims 10-11:
Byrne is silent on conjugates of star-shaped polypeptides, which stimulating cell growth or inducing of tissue regeneration or angiogenesis etc.
However, Byrne suggest that star-shaped polypeptides are an attractive class of molecules for use as gene delivery vectors owing to their potential improved biocompatibility, structural characteristics and therapeutic “cargo” capacity [see section Conclusion in page 1232]. So, based on the guidance provided by Byrne a skilled person in the art would be motivated to incorporate peptide(s) on the star-shaped polypeptide, which stimulate cell growth or induce tissue regeneration or angiogenesis etc. For example, Sanchez-Gonzales teaches platelet-derived Growth Factors (GFs), which are biologically active peptides that enhance tissue repair mechanisms such as angiogenesis, extracellular matrix remodeling, and cellular effects as stem cells recruitment, chemotaxis, cell proliferation, and differentiation etc [see abstract]. So, these growth factors can be conjugated to star-shaped polypeptides of Byrne and arrive at applicants method with a reasonable expectation of success.
For claims 12 and 14:
Byrne is silent on conjugates of star-shaped polypeptides, which inhibit growth of bacteria, wherein bacteria is selected from E.coli, Staphylococcus and or Mycobacterium etc.
However, Byrne suggest that star-shaped polypeptides are an attractive class of molecules for use as gene delivery vectors owing to their potential improved biocompatibility, structural characteristics and therapeutic “cargo” capacity [see section Conclusion in page 1232]. So, based on the guidance provided by Byrne a skilled person in the art would be motivated to incorporate peptide(s) on the star-shaped polypeptide, which inhibit growth of bacteria. For example, Vorland teaches antimicrobial peptides that are active against E.coli [see abstract].
For claim 15:
The mode of administering by means of nebulizer or hydrogel or a scaffold are well known in the art, absent evidence to the contrary. It appears that applicants are already acknowledged this fact in their specification.
For claims 18 and 20-23:
Byrne teaches G5(64)-PLL5, which is identical to applicants elected star peptide [see Figures 5-7].
For claim 24:
Byrne is silent on conjugates of star-shaped polypeptides, which treats alpha-1-antitrypsin deficiency.
However, Byrne suggest that star-shaped polypeptides are an attractive class of molecules for use as gene delivery vectors owing to their potential improved biocompatibility, structural characteristics and therapeutic “cargo” capacity [see section Conclusion in page 1232]. So, based on the guidance provided by Byrne a skilled person in the art would be motivated to incorporate peptide(s) on the star-shaped polypeptide, which treats alpha-1-antitrypsin deficiency.
For claim 25:
The mode of administering by inhalation, such as nebulizer, is well known in the art, absent evidence to the contrary. It appears that applicants are already acknowledged this fact in their specification.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, star shaped polypeptides and their advantages in delivering organic compounds, nucleic acids and peptides etc., were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art.
The motivation to combine can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed method with a reasonable expectation of success.
The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. In re Sernaker, 702 F.2d 989, 994-95, 217 USPQ 1, 5-6 (Fed. Cir. 1983).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUDHAKAR KATAKAM whose telephone number is (571)272-9929. The examiner can normally be reached 8:30 am to 5 pm.
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SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658