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 .
DETAILED ACTION
1. Preliminary amendment and claims 1-9 filed on 9/11/24 is acknowledged.
2. Priority
Receipt is acknowledged of papers (foreign priority filed 4/26/23) submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
3. IDS filed 9/19/24 is acknowledged. A signed copy of the IDS is provided with this Office Action.
4. Drawings
The drawings filed on 9/11/24 are acknowledged.
5. Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant's cooperation is requested in correcting any errors of which applicant may become aware in the specification.
6. Written Description
Claims 1-9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, as containing 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(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-9 of the instant application as interpreted are directed to the following genus claims.
1. An angiotensin converting enzyme 2 (ACE2) homologous peptide, comprising one of the following sequences:
QEQAQTYLDGYNKTYQDLVYKDNLAQWTLNT (SEQ ID NO: 1) VTQQAQMFLEEFNRRAENISYESSLASWDYNT (SEQ ID NO: 2) EENAKTFLNNFNQEAEDLSYQSSLASWNYNT (SEQ ID NO: 3) VENKANEFLQKFDEEATRRMYQYSLASWAYNT (SEQ ID NO: 4) RQQAQTYLDSYNKTYQDLIYKDNLAQWTLNT (SEQ ID NO: 5) VTQQAAEFLLQFNINAENRSYESSLASWDYNT (SEQ ID NO: 6) VPQNVTTFLNQFNQNAEGLYYESSLASWAYNT (SEQ ID NO: 7).
2. The ACE2 homologous peptide according to claim 1, comprising the following sequence: (SEQ ID NO: 1) QEQAQTYLDGYNKTYQDLVYKDNLAQWTLNT.
3. The ACE2 homologous peptide according to claim 1, comprising the following sequence: (SEQ ID NO: 2) VTQQAQMFLEEFNRRAENISYESSLASWDYNT.
4. The ACE2 homologous peptide according to claim 1, comprising the following sequence: (SEQ ID NO: 3) EENAKTFLNNFNQEAEDLSYQSSLASWNYNT.
5. The ACE2 homologous peptide according to claim 1, comprising the following sequence: (SEQ ID NO: 4) VENKANEFLQKFDEEATRRMYQYSLASWAYNT.
6. The ACE2 homologous peptide according to claim 1, comprising the following sequence: (SEQ ID NO: 5) RQQAQTYLDSYNKTYQDLIYKDNLAQWTLNT.
7. The ACE2 homologous peptide according to claim 1, comprising the following sequence: (SEQ ID NO: 6) VTQQAAEFLLQFNINAENRSYESSLASWDYNT.
8. The ACE2 homologous peptide according to claim 1, comprising the following sequence: (SEQ ID NO: 7) VPQNVTTFLNQFNQNAEGLYYESSLASWAYNT.
9. A pharmaceutical composition, comprising the ACE2 homologous peptide according to claim 1, wherein the pharmaceutical composition competitively inhibits a binding of a receptor-binding domain region of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) with ACE2 in host cells.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. For a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
“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., 119, F.3d 1559, 1568, 43 USPQ2d 1398, 1405 (Fed. Cir. 1997).
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the biomolecule, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule.”
“The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice …, reduction to drawings …, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.” MPEP 2163.
Furthermore, a “‘representative number of species’ means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure ‘indicates that the patentee has invented species sufficient to constitute the gen[us].’ See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (‘[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.’). ‘A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.’ In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).” MPEP 2163.
In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, the Court of Appeals for the Federal Circuit has held that “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”. As indicated in MPEP § 2163, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that a representative number of species means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163.
In the instant case, there is no function associated with structure with regard to the members of genus of “angiotensin converting enzyme 2 (ACE2) homologous peptide, comprising one of SEQ ID Nos.1-7; which as written can also read on any genomic sequence(s) of ACE2 peptide(s). Further no pharmaceutical compositions are described. It is neither taught nor any data is provided for using the short ACE2 peptide(s) of SEQ ID Nos. 1-7 in pharmaceutical compositions for the treatment of any of the diseases or disorders. There is no evidence presented that ACE2 peptide(s) of SEQ ID Nos. 1-7 is associated with any of the known diseases or disorders or can be treated by administering the ACE2 peptide(s) of SEQ ID Nos. 1-7.
No information, beyond the characterization of a few short peptides drawn to “An angiotensin converting enzyme 2 (ACE2) homologous peptide, consisting of one of the sequences of SEQ ID Nos. 1-7, which competitively inhibits binding of a receptor-binding domain region of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) with ACE2 in host cells; has been provided by the applicants’, which would indicate that they had possession of the claimed genus of ACE2 polypeptides.
The genus of polypeptides and the encoding polynucleotides required in the claimed invention is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of polypeptides is adequately described by the disclosure of the structures of SEQ ID NOs: 1-7, with specific structures having the associated function/activity, since one could use structural homology to isolate those polypeptides and the encoding polynucleotides recited in the claims. The art clearly teaches the “Practical Limits of Function Prediction”:
(a) Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and (iv) conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that “Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105). Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105). Applicants’ are respectfully directed to the problems associated EC Classification in the section “Transferring the EC Classification enzyme to Non-Enzyme Comparisons”; pages 101-102 and Fig. 2a)-b), highlighting the structural and functional heterogeneity based on EC Classification numbers; as the stereo-specificity, substrate-specificity and catalytic properties vary widely.
(b) Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340) also highlight the difficulties associated with “Prediction of protein function from protein sequence and structure”; “To reason from sequence and structure to function is to step onto much shakier ground”, closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer (page 309, paragraph 4), it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given three protein functions, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions (page 312, paragraph 5), in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity (page 313, paragraph 4), although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein’s role fundamentally (page 323, paragraph 1).
(c) This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polynucleotides and encoded polypeptides do not necessarily share the same function. For example, Witkowski et al., (Biochemistry 38:11643-11650, 1999), teaches that one conservative amino acid substitution transforms a b-ketoacyl synthase into a malonyl decarboxylase and completely eliminates b-ketoacyl synthase activity.
As stated above, No information, beyond the characterization of a few short peptides drawn to “An angiotensin converting enzyme 2 (ACE2) homologous peptide, consisting of one of the sequences of SEQ ID Nos. 1-7, which competitively inhibits binding of a receptor-binding domain region of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) with ACE2 in host cells is described.
As the claimed genera of polypeptides having widely variable structures and no associated function, correlating structure with function has been provided. Furthermore, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features” (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895).
Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. Applicants are referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
7. Pharmaceutical composition
Claim 9 is rejected under 35 U.S.C. § 112, first paragraph, as the disclosure is enabling only for claims limited to - An angiotensin converting enzyme 2 (ACE2) homologous peptide, consisting of one of the sequences of SEQ ID Nos. 1-7, which competitively inhibits binding of a receptor-binding domain region of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) with ACE2 in host cells.
Factors to be considered in determining whether undue experimentation is required, are summarized in re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988) [ Ex parte Forman [230 USPQ 546 (Bd. Pat. App. & Int. 1986)]. The Wands factors are: (a) the quantity of experimentation necessary, (b) the amount of direction or guidance presented, (c) the presence or absence of working example, (d) the nature of the invention, (e) the state of the prior art, (f) the relative skill of those in the art, (g) the predictability or unpredictability of the art, and (h) the breadth of the claim.
It is neither taught nor any data is provided for using the sequences of SEQ ID Nos. 1-7 in pharmaceutical compositions for the treatment of any of the diseases or disorders. There is no evidence presented that any of the sequences of SEQ ID Nos. 1-7 is associated with any of the known diseases or disorders or can be treated by administering the sequences of SEQ ID Nos. 1-7. Without such a data or evidence, claims to pharmaceutical composition comprising any of the sequences of SEQ ID Nos. 1-7, would amount to a composition or potential drug for treatment for any disorder or disease, which is not enabled. Given the lack of direction or guidance and the nature of the invention, obtaining such a composition for one of skill in the art would be highly unpredictable. This is because the polypeptide when associated with a particular disease or disorder would be expressed differentially. Manipulating or controlling these levels depends upon the disease or disorder, and may not always be controlled by supplementing with such a polypeptide(s) composition. Further, no guidance in provided, pertaining to the fate of the administrated polypeptide(s) in vivo.
Since it is not routine in the art to engage in de novo experimentation to prepare numerous compositions where the expectation "of success is unpredictable", the skilled artisan would require additional guidance, specific to individual disorder or disease, in order to make and use pharmaceutical compositions in a manner reasonably commensurate with the scope of the claims. Without such guidance, the experimentation left to those skilled in the art is undue.
8. 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) 1-8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Accession Numbers as noted against the claimed sequences and are 100% identical to the claimed sequences. In the instant case, there is no function associated with structure with regard to the members of genus of “angiotensin converting enzyme 2 (ACE2) homologous peptide, comprising any one of SEQ ID Nos.1-7; which as written can also read on any genomic sequence(s) of ACE2 peptide(s). Perhaps using ‘consisting of’ instead of ‘comprising’ may have a different effect.
SEQ ID NO: 2 vs AC A0A091LIW5
A0A091LIW5_9AVES
ID A0A091LIW5_9AVES Unreviewed; 803 AA.
AC A0A091LIW5;
DT 26-NOV-2014, integrated into UniProtKB/TrEMBL.
DT 26-NOV-2014, sequence version 1.
DE RecName: Full=Angiotensin-converting enzyme
DE EC=3.4.-.- {ECO:0000256|RuleBase:RU361144};
GN ORFNames=N324_00522 {ECO:0000313|EMBL:KFP42826.1};
OS Chlamydotis macqueenii (Macqueen's bustard).
PNG
media_image1.png
258
978
media_image1.png
Greyscale
SEQ ID NO: 3 (Rao et al.) vs. AC: BKB51145
PNG
media_image2.png
644
989
media_image2.png
Greyscale
PNG
media_image3.png
297
957
media_image3.png
Greyscale
SEQ ID NO: 4 vs. AC: A0A6A5FEK4
PNG
media_image4.png
224
1119
media_image4.png
Greyscale
PNG
media_image5.png
117
983
media_image5.png
Greyscale
PNG
media_image6.png
246
1022
media_image6.png
Greyscale
SEQ ID NO: 1 vs. ACA1K1RQC0
PNG
media_image7.png
165
778
media_image7.png
Greyscale
ANGIOTENSIN-CONVERTING ENZYME; 1
PNG
media_image8.png
243
1078
media_image8.png
Greyscale
SEQ ID NO: 5 vs. AC:AOA3E1NTC7
PNG
media_image9.png
137
776
media_image9.png
Greyscale
Chitinophaga silvisoli
ANGIOTENSIN-CONVERTING ENZYME; 1
PNG
media_image10.png
250
1033
media_image10.png
Greyscale
SEQ ID NO: 6 vs. AC:: G1KTF3
PNG
media_image11.png
159
714
media_image11.png
Greyscale
Anolis carolinensis (American chameleon)
ANGIOTENSIN-CONVERTING ENZYME
PNG
media_image12.png
247
1006
media_image12.png
Greyscale
SEQ ID NO: 7 vs. AC: A0A151N089
PNG
media_image13.png
115
755
media_image13.png
Greyscale
Alligator mississippiensis (American alligator).
ANGIOTENSIN-CONVERTING ENZYME
PNG
media_image14.png
237
1023
media_image14.png
Greyscale
9. No claim is allowed.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to TEKCHAND SAIDHA whose telephone number is (571)272-0940. The examiner can normally be reached on M-F 8.00-5.30. 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, Robert B Mondesi can be reached on 408 918 7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TEKCHAND SAIDHA/
Primary Examiner, Art Unit 1652
Recombinant Enzymes, Hoteling
Telephone: (571) 272-0940
Fax: (571) 273-0940
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