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
Application Status
This application is a US Non-Provisional Patent application filed on 12/15/2022.
Claims 1-20 are currently pending in the instant patent application.
The claims set filed on 12/15/2022 is acknowledged.
Election/Restriction
Applicant's election without traverse of Group III, Claims 1, 8, 13-15 and 17 (in part), drawn to a mammalian cell, comprising: one or more promoters operably connected to one or more gas vesicle (GV) polynucleotides comprising: one or more gas vesicles assembly (GVA) gene(s) encoding one or more GVA protein(s); and one or more gas vesicle structural (GVS) gene(s) encoding one or more GVS protein(s), wherein the one or more GVA protein(s) and the one or more GVS protein(s) are capable of forming gas vesicles (GVs) upon expression in the mammalian cell, and wherein said GVs are capable of producing nonlinear ultrasound contrast, wherein the expression of the GVs within the mammalian cell is capable of being detected via dynamic non-destructive imaging, and wherein the dynamic non-destructive imaging comprises: nonlinear ultrasound imaging; cross-propagating amplitude modulation pulse sequence (xAM) imaging; and/or parabolic AM (pAM) imaging in the response filed on October 27, 2025 is acknowledged.
After careful review, the Examiner is hereby considering to withdrew restriction requirement between Groups III and I, the claims of Group III and I are under consideration.
Claims 2-4, 9-12, 16 and 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicants request for rejoinder is noted. However, current claims of elected Group III are not allowable at this time. When Group I would be allowable, rejoinder request would be evaluated at that time.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1,5-6, 7, 8, 13-15 and 17 are present for examination.
Priority
Acknowledgement is made of applicants claim for priority of US Provisional applications 63/420,147, filed on 10/28/2022, 63/290425, filed on 12/16/2021, and 63/290,402, filed on 12/16/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/22/2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are considered by the examiner. The signed copy of 1449 is enclosed herewith.
Drawings Objections
Drawings submitted on 12/15/2022 are not accepted by the Examiner because text in the figures and few Figures are not clearly legible. Appropriate correction is required.
Claim Objections
Claims 1 and 14 are objected to in the recitation “operably connected to”, which should be changed to “operably linked to”. Appropriate correction is required.
Claim 6 is objected to in the recitation “therapeutic cell configured”, which should be changed to “therapeutic cell comprising”. Appropriate correction is required.
Claims 13 is objected to in the recitation “are selected from the group comprising gvpA, gvpC, gvpN, gvpJ, gvpK, gvpF, gvpG, gvpV, gvpW, or any combination thereof, which should be changed to “are selected from the group consisting of gvpA, gvpC, gvpN, gvpJ, gvpK, gvpF, gvpG, gvpV, and gvpW, or any combination thereof”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claim 15 is rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 15 is indefinite in the recitation “portion” in the context of GVA or GVA protein, wherein the phrase “portion” is a relative term, because it does not have any boundary of said GVA or GVS protein sequence, regarding its length and location, which is unknown, renders the claim indefinite. The term is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. See MPEP 2173.05(b), part (I). Clarification is required.
Claim 17 is rejected under 35 U.S.C. 112(b) or second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 17 is indefinite in the recitation “at least about” in the context of 5 day for robust mutations. It is unclear whether applicant meant “at least 5 days” or “about 5 days”. However, “about 5 days” is unclear and vague, as it is not clearly stated in the specification about what is the scope of “about 5 days” mean? In addition, the combination of “at least about 5 days” is ambiguous and confusing. Besides, the term “about” is a term of degree and the examiner has reviewed the specification and can find no examples or teachings that can be used for ascertaining the variance intended by the recited term of degree. Moreover, there is nothing in the specification or prior art of record to indicate that one of ordinary skill in the art could have ascertain the scope of the recited degree. It is suggested that applicant clarify the meaning of the claim.
Claim Rejections - 35 USC § 112(a)
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.
A. Written Description
Claims 1, 5-7, 8, 13-15 and 17 are rejected under 35 U.S.C. 112(a), 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1 and 15 are directed to a mammalian cell, comprising: any one or more promoters operably connected to one or more gas vesicle (GV) polynucleotides comprising: one or more gas vesicles assembly (GVA) gene(s) encoding one or more GVA protein(s); and one or more gas vesicle structural (GVS) gene(s) encoding one or more GVS protein(s), wherein the one or more GVA protein(s) and the one or more GVS protein(s) are capable of forming gas vesicles (GVs) upon expression in the mammalian cell, and wherein said GVs are capable of producing nonlinear ultrasound contrast, wherein the expression of the GVs within the mammalian cell is capable of being detected via dynamic non-destructive imaging, and wherein the dynamic non-destructive imaging comprises: nonlinear ultrasound imaging; cross-propagating amplitude modulation pulse sequence (xAM) imaging; and/or parabolic AM (pAM) imaging, wherein the mammalian cell comprises a DNA sequence that is at least 80% identical to SEQ ID NO: 2 or 3.
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.” University of California v. Eli Lilly and Co., 1997 U.S. App. LEXIS 18221, at *23, quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). To fully describe a genus of genetic material, which is a chemical compound, applicants must (1) fully describe at least one species of the claimed genus sufficient to represent said genus whereby a skilled artisan, in view of the prior art, could predict the structure of other species encompassed by the claimed genus and (2) identify the common characteristics of the claimed molecules, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these (paraphrased from Enzo Biochemical).
Thus, Claims are drawn to any mammalian cell, comprising: any one or more promoters operably connected to any one or more gas vesicle (GV) polynucleotides comprising: any one or more gas vesicles assembly (GVA) gene(s) encoding any one or more GVA protein(s); and any one or more gas vesicle structural (GVS) gene(s) encoding one or more GVS protein(s), wherein the one or more GVA protein(s) and the one or more GVS protein(s) are capable of forming gas vesicles (GVs) upon expression in the mammalian cell, and wherein said GVs are capable of producing nonlinear ultrasound contrast, wherein the expression of the GVs within the mammalian cell is capable of being detected via dynamic non-destructive imaging, and wherein the dynamic non-destructive imaging comprises: nonlinear ultrasound imaging; cross-propagating amplitude modulation pulse sequence (xAM) imaging; and/or parabolic AM (pAM) imaging, wherein the mammalian cell comprises any DNA sequence that is at least 80% identical to SEQ ID NO: 2 or 3, i.e., any mammalian cell derived from any sources, any one or more promoters, any one or more gas vesicle (GV) polynucleotides, derived from any sources having no structure, any one or more GV Assembly protein(s) derived from any source having no structure, any one or more gas vesicle structural (GVS) gene(s) encoding any one or more GVS protein(s) derived from any source having no structure, and any DNA, which is at least 80% identical to SEQ ID NO: 2 or 3, which encompasses 20% non-identity that encompasses many DNAs, and many mammalian cells, many promoters, many GV proteins, many GVA proteins, many GVS proteins derived from many unknown sources, and many mutants, variants and fragments thereof, i.e., No Structure-Function correlation, which is required to fulfill the Written Description requirement.
As discussed in the written description guidelines 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. 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.
Thus, Claims are drawn to any mammalian cell derived from any sources, any one or more promoters, any one or more gas vesicle (GV) polynucleotides, derived from any sources having no structure, any one or more GV Assembly protein(s) derived from any source having no structure, any one or more gas vesicle structural (GVS) gene(s) encoding any one or more GVS protein(s) derived from any source having no structure, and any DNA, which is at least 80% identical to SEQ ID NO: 2 or 3, which encompasses 20% non-identity that encompasses many DNAs, or many promoters, and many mammalian cells, ,many GV proteins, many GVA proteins, many GVS proteins derived from many unknown sources, and many mutants, variants and fragments thereof, i.e., No Structure-Function correlation, which is required to fulfill the Written Description requirement.
As discussed in the written description guidelines 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. 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.
As discussed in the written description guidelines 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. 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.
Claims are drawn to any mammalian cell derived from any sources, any one or more promoters, any one or more gas vesicle (GV) polynucleotides, derived from any sources having no structure, any one or more GV Assembly protein(s) derived from any source having no structure, any one or more gas vesicle structural (GVS) gene(s) encoding any one or more GVS protein(s) derived from any source having no structure, and any DNA, which is at least 80% identical to SEQ ID NO: 2 or 3, which encompasses 20% non-identity that encompasses many DNAs, promoters, and many mammalian cells, ,many GV proteins, many GVA proteins, many GVS proteins derived from many unknown sources, and many mutants, variants and fragments thereof, which can have wide variety of unknown structures, whose structures are not fully described in the specification. No information, beyond the characterization of few mammalian cells, promoters, polynucleotides encoding GV proteins, GVA proteins, GVS proteins and two DNA fragments without function has been provided, which would indicate that applicants had possession of the claimed genus of DNAs, genes encoding proteins.
Furthermore, the genus of genes and encoded polypeptides and functional homologs or variants 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 and encoding polynucleotides are adequately described by the disclosure of the structures of prior art, i.e., genes associated with the production of amino acids, since one could use structural homology to isolate those polypeptides and the encoding polynucleotide recited in the claims. However, the art clearly teaches the “Practical Limits of Function Prediction”: Whisstock et al., (2003) 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, 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, 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, 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 (see, whole document). This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polypeptides do not necessarily share the same function and many functionally similar proteins will have little or no structural homology to disclosed proteins. For example, proteins having similar structure have different activities (structure does not always correlate to function); Witkowski et al., (1999) teaches that one conservative amino acid substitution transforms a -ketoacyl synthase into a malonyl decarboxylase and completely eliminates -ketoacyl synthase activity. Similarly, the art also teaches that functionally similar molecules have different structures; Kisselev L., (2002) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
As stated, no information, beyond the characterization of few mammalian cells, polynucleotides encoding GV proteins, GVA proteins, GVS proteins and two DNA fragments without function and promoters has been provide, which would indicate that applicants had possession of the claimed genus. The specification does not contain sufficient disclosure of the structure with function of all the mammalian cells, polynucleotides encoding GV proteins, GVA proteins, GVS proteins and two DNA fragments without function, and promoters has been provided within the scope of the claimed genus. The genus of polynucleotides, polypeptides claimed is a large variable genus including many mutants, variant and fragments thereof, which can have wide variety of structures. Therefore, many structurally unrelated proteins and DNAs within the scope of these claims. The specification discloses the structure of only few representative species of the claimed genus with mutations, which is insufficient to put one of skill in the art in possession of the attributes and features of all species within the claimed genus. 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.
Applicant is 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.
Conclusion
Status of the claims:
Claims 1, 5-7, 8, 13-15 and 17 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IQBAL H CHOWDHURY whose telephone number is (571)272-8137. The examiner can normally be reached on M-F, at 9:00-5:00 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached on 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Iqbal H. Chowdhury, Primary Patent Examiner
Art Unit 1656 (Recombinant Enzymes and Protein Crystallography)
US Patent and Trademark Office
Ph. (571)-272-8137 and Fax (571)-273-8137
/IQBAL H CHOWDHURY/
Primary Examiner, Art Unit 1656