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 Status
Claims 1-7 are pending.
Claims 1 and 7 are amended.
Claim Objections
Claim 4 is objected to because of the following informalities: the claim recites the “NAMPT-derived peptide binds to TLR4 or CYBB”. Examiner recommends defining TLR4 as the acronym is not defined in the specification. 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 2 (and claim 3 dependent from) 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.
With regards to claim 2 (and claim 3 dependent from), the claim recites “the NAMPT-derived peptide is a laminin a-1 derived peptide bound to an N-terminus or C-terminus”. It is unclear as to what defines an N-terminus or C-terminus that the laminin a-1-derived peptide is bound to and therefore it is unclear as to what the structure of the NAMP-derived peptide is. Therefore, the claim is indefinite.
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 1-7 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 treatment, does not reasonably provide enablement for prevention. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required, are summarized in In re Wands (858 F.2d 731, 8 USPQ 2nd 1400 (Fed. Cir. 1988)) as follows: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claim(s).
The specification defines “prevention” as all actions that inhibit inflammatory bowel disease or delay the onset of inflammatory bowel disease by administration of the composition.
The factors to be considered in making an enablement rejection were summarized above. 1) Preventing diseases requires identifying those patients who will acquire the condition before the symptoms occur. This would require extensive and potentially open-ended clinical research on healthy subjects (see Torres et al., The Lancet, Vol. 389, pg. 1741-1755; published 2017), 2-3) There is no working example of such a preventive procedure in man or animal in the specification 4) The claims rejected are drawn to clinical pharmacology and are therefore physiological in nature, 5) the state of the art is that no general procedure is art-recognized for determining which patients generally develop inflammatory bowel disease before the fact (see Bamias and Cominelli, Clin. Gastroenterol. Hepatol. Vol. 19, pg. 2469-2480; published 2017) 6) the artisan using the Applicants invention would need to be a Board Certified physician, 7) Despite intensive efforts, pharmaceutical science has been unable to find a way of identifying a pharmaceutical composition that is found to be effective for prevention of inflammatory bowel disease (see Kumar et al., Therap. Adv. Gastroenterol. Doi:10.1177/17562848221078456; published 2022). Under such circumstances, it is proper for the PTO to require evidence that such an unprecedented feat has actually been accomplished, In re Ferens, 163 USPQ 609. No such evidence has been presented in this case. The failure of skilled scientists to achieve such a goal is substantial evidence that achieving such a goal is beyond the skill of practitioners in that art. This establishes that it is not reasonable for any agent to be able to prevent inflammatory bowel disease. 8) the claims broadly read on prevention of all symptoms.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1 ( and claims 4-6 dependent from) and 7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claim(s) recite(s) “a nicotinamide phosphoribosyltransferase (NAMPT)-derived peptide as an active ingredient, wherein the NAMPT consists of SEQ ID NO: 1, and the NAMPT-derived peptide comprises at least one amino acid sequence selected from the group consisting of amino acids 57-65, amino acids 52 to 65, and amino acids 52-65 of NAMPT. This judicial exception is not integrated into a practical application because the additional elements do not contribute to any meaningful limitation to the natural product. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because claim 1 and claim 7 recites a nicotinamide phosphoribosyltransferase (NAMPT)-derived peptide wherein the NAMPT consists of SEQ ID NO: 1…”. The claims encompass a composition of a polypeptide that is structurally identical to a natural occurring polypeptide as evidenced by UniPro Database entry: (NAMPT_Human; deposited November 01, 1995) which discloses the sequence of a human nicotinamide phosphoribosyltransferase (alternate names: NAMPT, Visfatin, Pre-B cell-enhancing factor) that shares 100% sequence identity with SEQ ID NO:1 of the current instant application (see alignment below; residues 52-65 are highlighted in bold and underlined in the sequence alignment) and Romacho et al. (PLOS ONE, Vol 8, e78283; published October 10, 2013) who teach that human endothelial cells synthesize and release visfatin (NAMPT) in response to inflammation (see Abstract, pg. 1).
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 2591 100.0 491 1 AASEQ2_02242026_101923
ALIGNMENTS
RESULT 1
AASEQ2_02242026_101923
Query Match 100.0%; Score 2591; DB 1; Length 491;
Best Local Similarity 100.0%;
Matches 491; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MNPAAEAEFNILLATDSYKVTHYKQYPPNTSKVYSYFECREKKTENSKLRKVKYEETVFY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MNPAAEAEFNILLATDSYKVTHYKQYPPNTSKVYSYFECREKKTENSKLRKVKYEETVFY 60
Qy 61 GLQYILNKYLKGKVVTKEKIQEAKDVYKEHFQDDVFNEKGWNYILEKYDGHLPIEIKAVP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLQYILNKYLKGKVVTKEKIQEAKDVYKEHFQDDVFNEKGWNYILEKYDGHLPIEIKAVP 120
Qy 121 EGFVIPRGNVLFTVENTDPECYWLTNWIETILVQSWYPITVATNSREQKKILAKYLLETS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 EGFVIPRGNVLFTVENTDPECYWLTNWIETILVQSWYPITVATNSREQKKILAKYLLETS 180
Qy 181 GNLDGLEYKLHDFGYRGVSSQETAGIGASAHLVNFKGTDTVAGLALIKKYYGTKDPVPGY 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GNLDGLEYKLHDFGYRGVSSQETAGIGASAHLVNFKGTDTVAGLALIKKYYGTKDPVPGY 240
Qy 241 SVPAAEHSTITAWGKDHEKDAFEHIVTQFSSVPVSVVSDSYDIYNACEKIWGEDLRHLIV 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 SVPAAEHSTITAWGKDHEKDAFEHIVTQFSSVPVSVVSDSYDIYNACEKIWGEDLRHLIV 300
Qy 301 SRSTQAPLIIRPDSGNPLDTVLKVLEILGKKFPVTENSKGYKLLPPYLRVIQGDGVDINT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 SRSTQAPLIIRPDSGNPLDTVLKVLEILGKKFPVTENSKGYKLLPPYLRVIQGDGVDINT 360
Qy 361 LQEIVEGMKQKMWSIENIAFGSGGGLLQKLTRDLLNCSFKCSYVVTNGLGINVFKDPVAD 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LQEIVEGMKQKMWSIENIAFGSGGGLLQKLTRDLLNCSFKCSYVVTNGLGINVFKDPVAD 420
Qy 421 PNKRSKKGRLSLHRTPAGNFVTLEEGKGDLEEYGQDLLHTVFKNGKVTKSYSFDEIRKNA 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 PNKRSKKGRLSLHRTPAGNFVTLEEGKGDLEEYGQDLLHTVFKNGKVTKSYSFDEIRKNA 480
Qy 481 QLNIELEAAHH 491
|||||||||||
Db 481 QLNIELEAAHH 491
Because there is no difference in characteristics (structural, functional, or otherwise) between the claimed and naturally occurring composition, the claimed composition does not have markedly different characteristics and thus is a product of nature exception. Accordingly, the product is directed to an exception (Step 2A: Yes). Because the claims do not include any additional features that could add significantly more to the exception (Step 2B: No), the claims do not qualify as eligible subject matter and are rejected.
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.
(g)(1) during the course of an interference conducted under section 135 or section 291, another inventor involved therein establishes, to the extent permitted in section 104, that before such person’s invention thereof the invention was made by such other inventor and not abandoned, suppressed, or concealed, or (2) before such person’s invention thereof, the invention was made in this country by another inventor who had not abandoned, suppressed, or concealed it. In determining priority of invention under this subsection, there shall be considered not only the respective dates of conception and reduction to practice of the invention, but also the reasonable diligence of one who was first to conceive and last to reduce to practice, from a time prior to conception by the other.
A rejection on this statutory basis (35 U.S.C. 102(g) as in force on March 15, 2013) is appropriate in an application or patent that is examined under the first to file provisions of the AIA if it also contains or contained at any time (1) a claim to an invention having an effective filing date as defined in 35 U.S.C. 100(i) that is before March 16, 2013 or (2) a specific reference under 35 U.S.C. 120, 121, or 365(c) to any patent or application that contains or contained at any time such a claim.
Claims 1, 4 and 7 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Samal et al. (US Patent Number: 5,874,399; published February 23, 1999), hereinafter referred to as Samal et al., as evidenced by Gasparrini et al. (Journal of Biological Chemistry, Vol. 298, 101669; published February 02, 2022), hereinafter referred to as Gasparrini et al.
With regards to claims 1, 4, and 7, Samal et al. disclose a pharmaceutical composition comprising a progenitor B cell stimulating factor (PBSF; also known as NAMPT) that has the amino acid sequence of SEQ ID NO. 2 (which is 100% identical to the amino acid sequence of SEQ ID NO. 1 of the current instant application) (see Column 2, lines 53-60) and which also comprises at least one amino acid sequence selected from the group consisting of amino acids 57 to 65, amino acids 52 to 56, and amino acids 52 to 65 of NAMPT” (see bold and underlined residues in sequence alignment below). Claim 4 is anticipated by the inherent ability of NAMPT to bind to TLR4 as evidenced by Gasparrini et al. who demonstrate the binding of NAMPT to TLR4 (see pg. 5, Kinetics of NAMPT interaction with immobilized TLR4).
Query Match 100.0%; Score 2591; Length 491;
Best Local Similarity 100.0%;
Matches 491; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MNPAAEAEFNILLATDSYKVTHYKQYPPNTSKVYSYFECREKKTENSKLRKVKYEETVFY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MNPAAEAEFNILLATDSYKVTHYKQYPPNTSKVYSYFECREKKTENSKLRKVKYEETVFY 60
Qy 61 GLQYILNKYLKGKVVTKEKIQEAKDVYKEHFQDDVFNEKGWNYILEKYDGHLPIEIKAVP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLQYILNKYLKGKVVTKEKIQEAKDVYKEHFQDDVFNEKGWNYILEKYDGHLPIEIKAVP 120
Qy 121 EGFVIPRGNVLFTVENTDPECYWLTNWIETILVQSWYPITVATNSREQKKILAKYLLETS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 EGFVIPRGNVLFTVENTDPECYWLTNWIETILVQSWYPITVATNSREQKKILAKYLLETS 180
Qy 181 GNLDGLEYKLHDFGYRGVSSQETAGIGASAHLVNFKGTDTVAGLALIKKYYGTKDPVPGY 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GNLDGLEYKLHDFGYRGVSSQETAGIGASAHLVNFKGTDTVAGLALIKKYYGTKDPVPGY 240
Qy 241 SVPAAEHSTITAWGKDHEKDAFEHIVTQFSSVPVSVVSDSYDIYNACEKIWGEDLRHLIV 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 SVPAAEHSTITAWGKDHEKDAFEHIVTQFSSVPVSVVSDSYDIYNACEKIWGEDLRHLIV 300
Qy 301 SRSTQAPLIIRPDSGNPLDTVLKVLEILGKKFPVTENSKGYKLLPPYLRVIQGDGVDINT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 SRSTQAPLIIRPDSGNPLDTVLKVLEILGKKFPVTENSKGYKLLPPYLRVIQGDGVDINT 360
Qy 361 LQEIVEGMKQKMWSIENIAFGSGGGLLQKLTRDLLNCSFKCSYVVTNGLGINVFKDPVAD 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LQEIVEGMKQKMWSIENIAFGSGGGLLQKLTRDLLNCSFKCSYVVTNGLGINVFKDPVAD 420
Qy 421 PNKRSKKGRLSLHRTPAGNFVTLEEGKGDLEEYGQDLLHTVFKNGKVTKSYSFDEIRKNA 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 PNKRSKKGRLSLHRTPAGNFVTLEEGKGDLEEYGQDLLHTVFKNGKVTKSYSFDEIRKNA 480
Qy 481 QLNIELEAAHH 491
|||||||||||
Db 481 QLNIELEAAHH 491
Therefore, claims 1, 4 and 7 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Samal et al. ( US Patent Number: 5,874,399; published February 23, 1999), hereinafter referred to as Samal et al., as evidenced by Gasparrini et al. (Journal of Biological Chemistry, Vol. 298, 101669; published February 02, 2022).
Claims 1-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim et al. (Antioxidants, Vol 11, doi.org/10.3390/antiox11122376; published November 30, 2022), hereinafter referred to as Kim et al..
With regards to claims 1 (and claims 2-6 dependent from) and claim 7, Kim et al. teach the use of a plasmid encoding NAMPT residues 1-491 (see section, 2.4 Plasmid Construction, pg. 3). Although Kim et al. do not disclose the sequence of NAMPT, the sequence is viewed as inherent as evidenced by UniProt Database entry: NAMPT_Human which discloses the sequence of human nicotinamide phosphoribosyltransferase that shares 100% sequence identity with SEQ ID NO:1 (see sequence alignment above under 101 rejection). Kim et al. further disclose the use of NAMPT peptides, amino acids 57-65, amino acids 52-56, or amino acids 52-65 (see section 3.4, pg. 11).
With regards to claims 2-3, Kim et al. disclose the use of a 12-residue peptide TWYKIAFQRNRK (designated TK) that is derived from the COOH-terminal globular domain of laminin-1 a1 chain, as a vehicle for targeted drug delivery to the colon (see section 3.5, pg. 13). The 12-residue TWYKIAFQRNRK peptide (TK) shares 100% sequence identity with SEQ ID NO:2 of claim 3 of the current instant application. Kim et al. further disclose the development of the 12-residue TK peptide designated as colon-targeted (CT)-conjugated multifunctional NAMPT (rcT-NAMPT) comprising CT (TWYKIAFQRNRK) as the colon-targeting moiety which harbors the minimal essential residues required for CYBB/TLR4 binding (see abstract, pg. 1). Kim et al. disclose that to obtain recombinant rCT-NAMPT proteins, colon-targeting sequences of NAMPT amino acids (57-65), NAMPT amino acids (52-65), and CT peptides (TWYKIAFQRNRK) were cloned with an N-terminal 6xHis tag into the pRSFDuet-1 vector (see section 2.6 recombinant protein, pg. 4). Kim et al. disclose an example of such a rCT-NAMPT in Figure 5, panel A (see pg. 13) where the TWKYKIAFQRNRK is at the N-terminus of the NAMPT-peptide.
With regards to claim 4, Kim et al. discloses that eNAMPT directly binds with CYBB or TLR4 (see Figure 2, pg. 9).
With regards to claims 5-6, Kim et al. discloses that an NAMPT peptide inhibits activation of the NLRP3 Inflammasome. Specifically, Kim et al. disclose that TAT-NAMPT peptides (amino acids 52-65) partially inhibited NLRP3 inflammasome activation (see Figure 4, pg. 12). Kim et al. further disclose evidence that the NAMPT peptide (amino acids 52-65) is an essential negative regulator of signal 1 and signal 2 (reduced inflammation) in response to NLRP3 inflammasome activation.
Therefore, claims 1-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim et al. (Antioxidants, Vol 11, doi.org/10.3390/antiox11122376; published November 30, 2022).
Relevant Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Huang et al., Inflammation, Vol. 43, DOI: 10.1007/s10753-019-01166-z (2020)
Ren et al., Drug Delivery, Vol. 23, pg. 1763-1772 (2016)
Manago et al., Nature Communications, DOI: 10.1038/s41467-019-12055-2 (2019)
Camp et al, Scientific Reports, DOI: 10.1038/srep13135 (2015)
Conclusion
No claims are allowed.
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/GEORGE THEMISTOCLIS LOUNTOS/ Examiner, Art Unit 1652
/RICHARD G HUTSON/ Primary Examiner, Art Unit 1652