DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's election without traverse of Group I, heparan sulfate 2-0-sulphotransferase (HS2ST, species from Group H), and sulfatase 2 (Sulf2, species from Group J) in the reply filed on 08/22/2025 is acknowledged. Claims 91-97 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention. The requirement is still deemed proper and is therefore made FINAL.
Claims 59, 70-77, 99, 100, heparan sulfate 2-0-sulphotransferase (HS2ST, species from Group H), and sulfatase 2 (Sulf2, species from Group J) are under consideration in this Office Action.
Title
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
Claim Rejections - 35 USC § 112(b) or 35 U.S.C. 112 (pre-AIA ) 2nd Paragraph
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 59, 70-77, 99, 100 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 pre-AIA the applicant regards as the invention.
Claim 59 recites the phrase “(a) growing a cell deficient or transgenic in one or more genes recited in Tables 1, 2, 4 or 5, using an appropriate growth media”. The metes and bounds of the claim are vague and indefinite because the claim is referencing limitations that are not set forth in either an independent claim or a dependent claim. A claim should not depend on tables or figures found in the specification for completeness but instead, should be able to stand alone. MPEP 2173.05(s) states that where possible, claims are to be complete in themselves. Incorporation by reference to a specific table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a table into the claim. Incorporation by reference is a necessity doctrine, not for applicant's convenience." Exparte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). Further, the specific nucleotide sequences and structures of the genes are not known and not recited in the claim. Dependent claims 70-77, 99, 100 are also rejected because they do not correct the defect.
Since the specification defines the term “transgenic” as referring to a genome that is modified to include additional genetic material encoding one or more genes of interest, then genes recited in the claims are not limited to any specific SEQ ID NO nucleotide sequences and structures of the genes and the recited cell encompasses any of the recited genes.
Claims 59, 70-77, 99, 100 are vague and indefinite since the claims do not recite specific methods steps for isolating and/or purifying the produced glycosaminoglycan including heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and/or hyaluronic acid.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 59, 70-77, 99, 100 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a broad and widely varying genus of methods of preparation of a substantially pure glycosaminoglycan selected from the group consisting of heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid comprising: (a) growing a genus of cells deficient or transgenic in one or more genus of genes of any nucleotide sequence and structure including variants and mutants thereof recited in Tables 1, 2, 4 or 5, using an appropriate growth media, (b) isolating the growth media from the cells by centrifugation. According to MPEP 2163:
“For each claim drawn to a genus: 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 (see i)(A), above), reduction to drawings (see i)(B), above), 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 (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014)…”
According to MPEP 2163.02:
“The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, "does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed." In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon "reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter." Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)).”
The reference of Kizer et al. (Appl Environ Microbiol. 2008 May;74(10):3229-41; PTO 892), which teaches that producing complex chemicals using synthetic metabolic pathways in microbial hosts is often complicated by deleterious interactions between pathway intermediates and the host cell metabolism [see p. 3229, abstract], noting that “… embedding a novel biochemical pathway in the metabolic network of a host cell can disrupt the subtle regulatory mechanisms that the cell has evolved over the millennia" [see p. 3229, column 1] and “[w]hile it can be relatively simple to determine that an engineered synthetic biochemical pathway is not functioning in the heterologous host, it is often a far more challenging task to determine exactly what is causing the problem” [p. 3237, column 2]. The reference of Prather et al. (Curr Opin Biotechnol. 2008 Oct;19(5):468-74; PTO 892) teaches numerous challenges associated with constructing de novo metabolic pathways, including selection of the appropriate enzymes in a multi-step pathway, compatibility of the enzymes with the expression host and with each other, and the requirement to engineer one or more of the enzymes to achieve the desired activity on a given substrate [see p. 472, columns 1-2]. Prather et al. specifically teach that “while synthetic biology provides a complementary framework for de novo pathway design, it is unclear how well some of the core principles, for example, Abstraction, can be implemented [see p. 472, column 2, top]. The reference of Chica et al. (Curr Opin Biotechnol. 2005 Aug;16(4):378-84; PTO 892) teaches that the complexity of the structure/function relationship in enzymes has proven to be the factor limiting the general application of rational enzyme modification and design, where rational enzyme modification and design requires in-depth understanding of structure/function relationships. The reference of Singh et al. (Curr Protein Pept Sci. 2017, 18, 1-11; PTO 892) reviews protein engineering methods including directed evolution, rational design, semi-rational design, and de-novo design; and states that despite the availability of a growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see entire publication especially Figs.1 and 3, and page 7, left column, lines 8-17). The reference teachings only provide guidance for searching and screening for the claimed genus of cells deficient or transgenic in one or more genus of genes recited in Tables 1, 2, 4 or 5, and genus of genes having any nucleotide sequence and structure including variants and mutants thereof.
The specification as originally filed does not disclose a representative number of species encompassed by the claimed genus by actual reduction to practice. The specification as originally filed does not provide a correlation between function and/or structure to enable one of ordinary skill in the art to predict which specific genes that are modified in the cell correlate with the cells being able to produce heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and/or hyaluronic acid.
Hence, the specification does not provide sufficient written description to inform one of ordinary skill in the art that applicants were in possession at the time the application was filed of the claimed genus of methods of preparation of a substantially pure glycosaminoglycan selected from the group consisting of heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid comprising: (a) growing a genus of cells deficient or transgenic in one or more genus of genes of any nucleotide sequence and structure including variants and mutants thereof recited in Tables 1, 2, 4 or 5, using an appropriate growth media, (b) isolating the growth media from the cells by centrifugation.
Claim Rejections - 35 USC § 103
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.
Claims 59, 70-77, 99, 100 are rejected under 35 U.S.C. 103 as being unpatentable over
US20110281817 (11/17/2011; PTO 892) in view of JP10257896 (09/29/1998, abstract; PTO 892), Morimoto-Tomita et al. (J. Biol. Chem. 277: 49175-49185, 2002; PTO 892), US20110244520 (10/06/2011; PTO 892).
US20110281817 teaches methods for producing hyaluronic acid are described, including altering the activity in Streptococcus cells of one or more enzymes and/or altering the amount of available substrates or substrate precursors (see entire publication and abstract especially paragraphs [0011]-[ [0028]). US20110281817 teaches the following in the claims:
1. A method for producing hyaluronic acid, wherein the method comprises growing Streptococcus cells in a culture medium, wherein the cells express the enzymes required for hyaluronic acid synthesis, wherein the activity or amount in the cells of one or more enzymes selected from:
(a) phosphoglucoisomerase;
(b) D-fructose-6-phosphate amidotransferase;
(c) phosphoglucosamine mutase;
(d) glucosamine-1-phosphate acetyl transferase;
(e) N-acetylglucosamine-1-phosphate pyrophosphorylase
(f) glucosamine-6-phosphate acetyl transferase; and
(g) phosphoacetylglucosamine mutase
has been increased, thereby producing hyaluronic acid.
2. The method according to claim 1, further comprising recovering the hyaluronic acid produced by the cells.
3. A method for producing hyaluronic acid, wherein the method comprises recovering hyaluronic acid from Streptococcus cells that express the enzymes required for hyaluronic acid synthesis, wherein the activity or amount in the cells of one or more enzymes selected from:
(a) phosphoglucoisomerase;
(b) D-fructose-6-phosphate amidotransferase;
(c) phosphoglucosamine mutase;
(d) glucosamine-1-phosphate acetyl transferase;
(e) N-acetylglucosamine-1-phosphate pyrophosphorylase
(f) glucosamine-6-phosphate acetyl transferase; and
(g) phosphoacetylglucosamine mutase
has been increased.
4. A method for producing hyaluronic acid, wherein the method comprises growing Streptococcus cells in a culture medium, wherein the cells express the enzymes required for hyaluronic acid synthesis, wherein the cells have been engineered or treated to increase the activity or amount in the cells of one or more enzymes selected from:
(a) phosphoglucoisomerase;
(b) D-fructose-6-phosphate amidotransferase;
(c) phosphoglucosamine mutase;
(d) glucosamine-1-phosphate acetyl transferase;
(e) N-acetylglucosamine-1-phosphate pyrophosphorylase
(f) glucosamine-6-phosphate acetyl transferase; and
(g) phosphoacetylglucosamine mutase
thereby producing hyaluronic acid.
5. The method according to claim 4, further comprising recovering the hyaluronic acid produced by the cells.
6. A method for producing hyaluronic acid, wherein the method comprises recovering hyaluronic acid from Streptococcus cells that express the enzymes required for hyaluronic acid synthesis, wherein the cells have been engineered or treated to increase the activity or amount in the cells of one or more enzymes selected from:
(a) phosphoglucoisomerase;
(b) D-fructose-6-phosphate amidotransferase;
(c) phosphoglucosamine mutase;
(d) glucosamine-1-phosphate acetyl transferase;
(e) N-acetylglucosamine-1-phosphate pyrophosphorylase
(f) glucosamine-6-phosphate acetyl transferase; and
(g) phosphoacetylglucosamine mutase
thereby producing hyaluronic acid.
7. The method according to claim 1, wherein the activity or amount in the cells of the one or more enzymes produces more UDP-N-acetyl glucosamine compared to wild type Streptococcus cells.
8. The method according to claim 1, wherein the hyaluronic acid produced is of a higher average molecular weight compared to wild type Streptococcus cells.
9. A method for producing hyaluronic acid, wherein the method comprises growing Streptococcus cells in a culture medium, wherein the cells express the enzymes required for hyaluronic acid synthesis; and providing one or more substrates selected from:
(a) UDP-N-acetylglucosamine;
(b) N-acetylglucosamine; and
(c) glucosamine
thereby producing hyaluronic acid.
10. The method according to claim 9, further comprising recovering the hyaluronic acid produced by the cells.
11. A method for producing hyaluronic acid, wherein the method comprises recovering hyaluronic acid from Streptococcus cells that express the enzymes required for hyaluronic acid synthesis, wherein one or more substrates selected from:
(a) UDP-N-acetylglucosamine;
(b) N-acetylglucosamine; and
(c) glucosamine
has been provided.
12. The method according to claim 9, further comprising providing one or more metabolites selected from:
(a) glutamine;
(b) acetyl-CoA; and
(c) UTP.
13. A method for producing hyaluronic acid, wherein the method comprises growing Streptococcus cells in a culture medium, wherein the cells express the enzymes required for hyaluronic acid synthesis, wherein the cells have been engineered or treated to increase the amount in the cells of one or more substrates selected from:
(a) UDP-N-acetylglucosamine;
(b) N-acetylglucosamine; and
(c) glucosamine
thereby producing hyaluronic acid.
14. The method according to claim 13, further comprising recovering the hyaluronic acid produced by the cells.
The teachings of the reference differ from the claims in that the reference does not teach that the cells are deficient or transgenic for heparan sulfate 2-0-sulphotransferase (HS2ST) and/or sulfatase 2 (Sulf2).
JP10257896 teaches heparan sulfate 2-sulfotransferase (HS2ST), which catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to L-iduronic acid at position 2 in heparan sulfate, purified from Chinese hamster ovary (CHO) cells and encoding cDNA (see attached abstract)
Morimoto-Tomita et al. teach the cloning of the full-length cDNA sequence for human and mouse SULF2 and expression in Chinese hamster ovary (CHO) cells (see entire publication and abstract especially EXPERIMENTAL PROCEDURES section, RESULTS section, and pages 49175- 49181).
US20110244520 teaches a method for producing a chondroitin, comprising (a) transferring the construct comprising a gene cluster comprising kpsF, kpsE, kpsD, kpsU, kpsC, kpsS, kfoA, kfoC, and kfoF to a non-pathogenic bacterial host cell, and (b) culturing the bacterial host cell under fermentation conditions wherein the chondroitin is produced by the bacterial host cell. US20110244520 teaches that the method for producing a chondroitin can include the step of purifying the recovered chondroitin where purification of chondroitin can be accomplished by any technique known in the art, including, for example, alkali treatment, acid treatment, proteinases treatment, chromatography, extraction, solvent extraction, membrane separation, electrodialysis, reverse osmosis, distillation, precipitation, chemical derivatization, crystallization, ultrafiltration, and/or precipitation of the polysaccharide using organic solvents. See entire publication and claims especially claims 34-61 and paragraphs [0115]- [0146]
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify and/or combine the reference teachings to make the claimed invention by modifying the method of US20110281817 where the cells are genetically modified to overexpress or delete the gene encoding heparan sulfate 2-sulfotransferase (HS2ST) as taught by JP10257896 and/or gene encoding sulfatase 2 (Sulf2) as taught by Morimoto-Tomita et al., growing the cells in appropriate growth media to produce the glycosaminoglycan, and isolating the growth media from the cells by centrifugation. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do this in order to obtain a simple method for producing a desired glycosaminoglycan including heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and/or hyaluronic acid. It would have been obvious in view of the above reference teachings including the teachings of US2011024452 to use any of the recited method steps including fractionating by ion exchange, nuclease digestion, protease digestion, and not using enzymes including chondoitinase as routine optimization and/or as desired for production of the desired heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and/or hyaluronic acid that is at least 95% free form protein and nucleic acid contamination. One of ordinary skill in the art at the time the invention was made would have a reasonable expectation of success because transforming host cells with nucleic acids to express protein and enzymes for producing desired products are known in the art as shown by the above reference teachings. Hence, the claimed invention as a whole is prima facie obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 59, 70-77, 99, 100 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 9, 10 of US Patent No. 11549000. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
The instant application is a continuation of Application Serial No. 16063670, now US Patent No. 11549000, published 01/10/2023. The claims and/or specification of the patent teach the claimed method of preparation of a substantially pure glycosaminoglycan selected from the group consisting of heparan sulfate, chondroitin sulfate, dermatan sulfate,keratan sulfate, and hyaluronic acid comprising: (a) growing a cell deficient or transgenic in one or more genes recited in Tables 1, 2, 4 or 5, using an appropriate growth media, and (b) isolating the growth media from the cells by centrifugation. Thus, the teachings anticipate the claimed invention.
Claims 59, 70-77, 99, 100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 44-47, 49, 51-53, 62 of Application Serial No. 16470164. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
The claims and/or specification of the copending applications teach the claimed method of preparation of a substantially pure glycosaminoglycan selected from the group consisting of heparan sulfate, chondroitin sulfate, dermatan sulfate,keratan sulfate, and hyaluronic acid comprising: (a) growing a cell deficient or transgenic in one or more genes recited in Tables 1, 2, 4 or 5, using an appropriate growth media, and (b) isolating the growth media from the cells by centrifugation. Thus, the teachings anticipate the claimed invention. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/CHRISTIAN L FRONDA/Primary Examiner, Art Unit 1652