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 .
Claims 1-34, 38 have been canceled. Claims 35-37, 39-41 remain pending.
Applicant's arguments filed 7-9-26 have been fully considered but they are not persuasive.
Do not use bold face type in amendments. It tends to read as a megaphone. You’ve already pointed out the new text by underlining which is sufficient.
There are discrepancies for support cited by applicants throughout the response filed 7-28-26. For example, support for claim 38, now incorporated into claim 35, is not in paragraph 199 as stated on pg 5 of the response. Paragraphs of the original disclosure matches the Published Application, so it is unclear where support for the changes lie.
When referencing the specification, please use page and paragraph number (and line number as necessary) of the original specification. Do not simply use paragraph numbers. Do not refer to paragraphs of the US Patent Application Publication because
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the following reasons: The application contains the sequence LWIY in claims 35 and 39 that is missing a SEQ ID NO. Applicants must file a “Sequence Listing” accompanied by directions to enter the listing into the specification as an amendment. Applicant also must provide statements regarding sameness and new matter with regards to the CRF and the “Sequence Listing.” Failure to fully comply with the sequence rules in response to the instant office action will be considered non-responsive.
Election/Restrictions
Applicants elected Group I, claims 35-39, with traverse in the reply filed on 12-29-25. The requirement remains FINAL. Claims 40 and 41 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention.
Claims 35-37, 39 remain pending.
Claim Objections
The claim objections have been withdrawn in view of the amendment.
Claim Rejections - 35 USC § 112
Written Description
Claims 35-37, 39 remain 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
A) The specification lacks written description for any transgenic non-human mammal whose genome comprises a “genetically modified myostatin gene in which 12 consecutive nucleotides encoding [ ] leucine, tryptophan, isoleucine, and tyrosine (LWIY) have been deleted from exon 2” that expresses a “pro-myostatin protein consisting of the amino acid sequence of SEQ ID NO: 30, 31, 32, or 33, wherein muscle mass of the non-human mammal is higher than a wild-type non-human mammal” as required in claim 35.
Claim 35 is drawn to “A transgenic non-human mammal whose genome comprises a genetically modified endoqenous myostatin gene in which 12 consecutive nucleotides encoding the amino acid sequence leucine, tryptophan, isoleucine, and tyrosine (LWIY) have been deleted from exon 2, wherein the transgenic non-human mammal expresses a pro-myostatin protein consisting of the amino acid sequence of SEQ ID NO: 30, 31, 32, or 33, and wherein muscle mass of the transgenic non-human mammal is higher than a wild-type non-human mammal.
The specification lacks written description for any “genetically modified myostatin gene in which 12 consecutive nucleotides encoding [ ] leucine, tryptophan, isoleucine, and tyrosine (LWIY) have been deleted from exon 2” in any non-human mammal as required in claim 35. The claim requires knowledge of the sequence of the myostatin gene in any species of myostatin gene in any elephant, gazelle, deer, antelope, elk, whale, dolphin, tiger, leopard, cheetah, dingo, wolf, beaver, mole, vole, otter, et al. The claim encompasses genetically modifying the myostatin gene of any elephant, gazelle, deer, antelope, elk, whale, dolphin, tiger, leopard, cheetah, dingo, wolf, beaver, mole, vole, otter, et al. The claim encompasses obtaining a genetically modified elephant, gazelle, deer, antelope, elk, whale, dolphin, tiger, leopard, cheetah, dingo, wolf, beaver, mole, vole, otter, et al. The claim encompasses modifying the muscle mass in any genetically modified elephant, gazelle, deer, antelope, elk, whale, dolphin, tiger, leopard, cheetah, dingo, wolf, beaver, mole, vole, otter, et al.
Pg 11, para 104, teaches: “In the present application, term ‘a conserved region of the myostatin gene by species’ includes nucleic acid sequences encoding 20 amino acids in the order of leucine, tryptophan, isoleucine, and tyrosine in conserved region of the myostatin (see Table 3).” Table 3 (pg 27) shows:
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But Table 3 and the specification and the art at the time of filing as a whole do not teach any specific non-mammalian myostatin gene sequences with the combination of 12 consecutive nucleotides encoding LWIY as required in claim 35. The specification does not teach the myostatin gene in any elephant, gazelle, deer, antelope, elk, whale, dolphin, tiger, leopard, cheetah, dingo, wolf, beaver, mole, vole, otter, et al. contains LWIY as encompassed by claim 35, nor does the specification teach deleting it in those species.
Crawford (WO 2008033042) taught a genetically modified cattle whose genome comprised a mutant myostatin gene, wherein the cattle exhibited increased muscle mass as compared to a wild-type cattle. The mutation was in exon 2 (nt419(del7-ins10)) which occurs in Maine-Anjou cattle (Grobet 1998) (pg 24, lines 5-11).
Pg 21, para 187, through pg 22, para 192, and Table 2, show the wild-type mature myostatin amino acid sequence.
Pg 31, para 271, says the sgRNAs in Table 5 (pg 32) target a sequence in Table 2, but actually they target wild-type nucleic acid sequences encoding wild-type myostatin.
Example 1 describes making sgRNA in Table 2 that target myostatin coding sequences.
Examples 2 and 3 describe isolating bovine oocytes and fertilizing them (pg 45-46).
Example 4 (pg 47) describes microinjecting fertilized bovine zygotes with mRNA encoding Cas9 and sgRNAs.
Example 5 (pg 48) describes implanting microinjected zygotes into recipient females such that calves were obtained.
Example 6-7 (pg 49) describe an assay for identifying the desired 12 base deletion in exon 2.
Example 8 (pg 50) describes off target assays.
Example 9 (pg 51) describes “targeted deep sequening”.
Example 10 (pg 53) describes performing the assay to identify the desired 12 base deletion and any off target effects.
Example 11 – part 1 (pg 54) describes assay the female offspring obtained to determine germline transmission. Eggs were collected from the offspring, fertilized, and transferred to a recipient female. The mutation was successfully transmitted to F1 offspring (pg 57, line 20). Pg 58, para 482, describes Fig. 17 which shows sequencing data from offspring with 12 nucleotides deleted.
Example 11 – part 2 (pg 58) describes assay the male offspring obtained to determine germline transmission. Sperm was collected from the offspring, used to fertilize eggs, and transferred to a recipient female. The mutation was successfully transmitted to F1 offspring (pg 57, line 20). Pg 59, para 487, describes Fig. 21 which shows sequencing data from offspring with 12 nucleotides deleted.
The specification is limited to a genetically modified cattle whose genome comprised a mutant myostatin gene, wherein the cattle exhibited increased muscle mass as compared to a wild-type cattle (Examples 1-11). sgRNAs were created to target exon 2 of an endogenous myostatin gene and make a 12 nucleotide deletion encoding leucine, tryptophan, isoleucine, and tyrosine (LWIY) (pg 3, lines 19-25; pg 9, lines 3-6; Fig. 4, SEQ ID NO: 7 that is -12 bp). Amino acids 156-159 of bovine or pig myostatin are LWIY; amino acids 157-159 of mouse myostatin are LWIY (pg 27, Table 3). The target sequence may be any of the nucleic acid sequences of SEQ ID NO: 38-60 (pg 28, para 249, through pg 30, para 256; Table 4).
The Examples do not teach the phenotype of the cattle obtained. Therefore, the specification lacks written description for any non-human mammal with the myostatin genetic modification that expresses SEQ ID NO: 30, 31, 32, or 33 and has increased muscle mass as required in claim 35.
The specification lacks written description for any species of non-human mammal that expresses a pro-myostatin that is no more or less than the amino acid sequence of SEQ ID NO: 30, 31, 32, or 33. The breadth of non-human mammals is discussed above. However, the SEQ ID NO: 30 is limited to a bovine myostatin protein, SEQ ID NO: 31 is a pig protein, SEQ ID NO: 32 is a mouse protein, and SEQ ID NO: 33 is a human protein (pg 19, para 176-179). The specification does not teach or infer expressing the mutated bovine myostatin protein of SEQ ID NO: 30 in any non-bovine non-human mammal as broadly encompassed by claim 35. The specification does not teach or infer expressing the mutated pig myostatin protein of SEQ ID NO: 30 in any non-pig non-human mammal as broadly encompassed by claim 35. The specification does not teach or infer expressing the mutated mouse myostatin protein of SEQ ID NO: 30 in any non-mouse non-human mammal as broadly encompassed by claim 35. The specification does not teach or infer expressing the mutated human myostatin protein of SEQ ID NO: 30 in any non-human mammal as broadly encompassed by claim 35. The specification does not teach SEQ ID NO: 30-33 are interchangeable and would work in any species from which they were foreign. The specification does not teach SEQ ID NO: 30-33 share significant homology that would allow them to function in any non-human mammal.
An adequate written description of genetically modified non-human mammal that expresses SEQ ID NO: 30,31,32,or 33 that has increased muscle mass requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it; what is required is a description of sequences, reagents, and final products. It is not sufficient to define a genetically modified non-human mammal solely by its principal biological property, i.e. expressing SEQ ID NO: 30,31,32 or 33 in the mammal and obtaining increased muscle mass, because disclosure of no more than that, as in the instant case, is simply a wish to know the identity of any non-human mammal that has those features. Naming a type of material generically known to exist in the absence of knowledge as to what that material consists of is not a description of that material. Claiming all non-human mammals that express SEQ ID NO: 30,31,32 or 33 and have increased muscle mass without defining what means will do is not in compliance with the description requirement. Rather, it is an attempt to preempt the future before it has arrived. Therefore, the concept lacks written description.
Response to arguments
Applicants point to para 162 (pg 17). Applicants’ argument is not persuasive. The paragraph does not teach any specific myostatin sequence in any non-mammalian species that encodes LWIY in exon 2. The paragraph does not contemplate deleting LWIY in exon 2.
Applicants point to para 175-179 and 199. Applicants’ argument is not persuasive. Para 175 says the animal expresses SEQ ID NO: 30, 31, 32, or 33. The paragraph does not contemplate expressing SEQ ID NO: 30, 31, 32, or 33 in non-bovine non-human mammals as encompassed by claim 35. The paragraph does not teach any specific myostatin sequence in any non-mammalian species that encodes LWIY in exon 2. The paragraph does not contemplate deleting LWIY in exon 2 as required in claim 35.
Para 176 says the animal is a bovine and the protein is SEQ ID NO: 30 “in which 4 amino acids are deleted” (this appears to be a translation error because SEQ ID NO: 30 already has 4 amino acids deleted). The paragraph is lacking the items cited above.
Para 177 says the animal is a pig and the protein is SEQ ID NO: 31 “in which 4 amino acids are deleted” (this appears to be a translation error because SEQ ID NO: 30 already has 4 amino acids deleted). The paragraph is lacking the items cited above.
Paragraphs 178, 179 contemplate mouse and human mutant myostatin proteins but are flawed for reasons set forth above.
Para 199 (pg 23) says the animal has 1-40% more muscle mass. Applicants’ argument is not persuasive for reasons set forth above.
Applicants conclude the claims are commensurate in scope with the specification. Applicants’ argument is not persuasive. The question is not whether the specification contemplated the scope. The question is whether the scope claimed has adequate written description. An adequate written description of genetically modified non-human mammal that expresses SEQ ID NO: 30,31,32,or 33 that has increased muscle mass requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it; what is required is a description of sequences, reagents, and final products. It is not sufficient to define a genetically modified non-human mammal solely by its principal biological property, i.e. expressing SEQ ID NO: 30,31,32 or 33 that has increased muscle mass, because disclosure of no more than that, as in the instant case, is simply a wish to know the identity of any non-human mammal that has those features. Naming a type of material generically known to exist in the absence of knowledge as to what that material consists of is not a description of that material. Claiming all non-human mammals that express SEQ ID NO: 30,31,32 or 33 and have increased muscle mass without defining what means will do is not in compliance with the description requirement. Rather, it is an attempt to preempt the future before it has arrived.
B) The specification lacks written description for “myostatin mRNA expression” in the transgenic animal being “less than that of a wild-type animal” as required in claim 36. The concept cannot be found in the specification or any of the examples. It is unclear how/why the transgenic animal would have less mRNA expression than a wild-type animal because the transgenic animal still expresses mutant myostatin mRNA and uses the same cell machinery to do so as compared to a wild-type animal. While the mRNA may encode mutant myostatin in a transgenic animal, the amount of mRNA MUST be the same as in a wild-type animal because the cell machinery is the same. Accordingly claim 36 lacks written description.
Response to arguments
Applicants argue paragraphs 28, 42, 166-169, 459-461 and Fig. 14 contemplate low myostatin mRNA expression. Applicants’ argument is not persuasive. Fig. 14 is limited to low mature myostatin mRNA expression in cattle 14 and 17 (pg 10, para 90); however, the claims are not.
C) The specification lacks written description for an engineered non-human mammalian cell whose genome comprises a “genetically modified myostatin gene in which 12 consecutive nucleotides encoding [ ] leucine, tryptophan, isoleucine, and tyrosine (LWIY) have been deleted from exon 2” that expresses a “pro-myostatin protein consisting of the amino acid sequence of SEQ ID NO: 30, 31, 32, or 33” as required in claim 39.
The specification lacks written description for any “genetically modified myostatin gene in which 12 consecutive nucleotides encoding [ ] leucine, tryptophan, isoleucine, and tyrosine (LWIY) have been deleted from exon 2” in any non-human mammal as required in claim 39 for reasons set forth in claim 35.
Pg 11, para 104, teaches: “In the present application, term ‘a conserved region of the myostatin gene by species’ includes nucleic acid sequences encoding 20 amino acids in the order of leucine, tryptophan, isoleucine, and tyrosine in conserved region of the myostatin (see Table 3).” Table 3 (pg 27) shows:
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But Table 3 and the specification and the art at the time of filing as a whole do not teach any specific non-mammalian myostatin gene sequences with the combination of 12 consecutive nucleotides encoding LWIY as required in claim 39. The specification does not teach the myostatin gene in any elephant, gazelle, deer, antelope, elk, whale, dolphin, tiger, leopard, cheetah, dingo, wolf, beaver, mole, vole, otter, et al. contains LWIY as encompassed by claim 39, nor does the specification teach deleting it in those species.
Crawford (WO 2008033042) is described above.
The teachings of the specification and the examples are described above. The specification is limited to a genetically modified cattle whose genome comprised a mutant myostatin gene, wherein the cattle exhibited increased muscle mass as compared to a wild-type cattle (Examples 1-11). sgRNAs were created to target exon 2 of an endogenous myostatin gene and make a 12 nucleotide deletion encoding leucine, tryptophan, isoleucine, and tyrosine (LWIY) (pg 3, lines 19-25; pg 9, lines 3-6; Fig. 4, SEQ ID NO: 7 that is -12 bp). Amino acids 156-159 of bovine or pig myostatin are LWIY; amino acids 157-159 of mouse myostatin are LWIY (pg 27, Table 3). The target sequence may be any of the nucleic acid sequences of SEQ ID NO: 38-60 (pg 28, para 249, through pg 30, para 256; Table 4).
The specification lacks written description for any species of non-human mammal cell that expresses a pro-myostatin that is no more or less than the amino acid sequence of SEQ ID NO: 30, 31, 32, or 33. The breadth of non-human mammals is discussed above. However, the SEQ ID NO: 30 is limited to a bovine myostatin protein, SEQ ID NO: 31 is a pig protein, SEQ ID NO: 32 is a mouse protein, and SEQ ID NO: 33 is a human protein (pg 19, para 176-179). The specification does not teach or infer expressing the mutated bovine myostatin protein of SEQ ID NO: 30 in any non-bovine non-human mammal as broadly encompassed by claim 39. The specification does not teach or infer expressing the mutated pig myostatin protein of SEQ ID NO: 30 in any non-pig non-human mammal as broadly encompassed by claim 39. The specification does not teach or infer expressing the mutated mouse myostatin protein of SEQ ID NO: 30 in any non-mouse non-human mammal as broadly encompassed by claim 39. The specification does not teach or infer expressing the mutated human myostatin protein of SEQ ID NO: 30 in any non-human mammal as broadly encompassed by claim 39. The specification does not teach SEQ ID NO: 30-33 are interchangeable and would work in any species from which they were foreign. The specification does not teach SEQ ID NO: 30-33 share significant homology that would allow them to function in any non-human mammal.
An adequate written description of genetically modified non-human mammal cell that expresses SEQ ID NO: 30,31,32,or 33 requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it; what is required is a description of sequences, reagents, and final products. It is not sufficient to define a genetically modified non-human mammal solely by its principal biological property, i.e. expressing SEQ ID NO: 30,31,32 or 33, because disclosure of no more than that, as in the instant case, is simply a wish to know the identity of any non-human mammal cell that has the genetic modification claimed and expresses SEQ ID NO: 30,31,32 or 33. Naming a type of material generically known to exist in the absence of knowledge as to what that material consists of is not a description of that material. Claiming all non-human mammal cells that have the genetic modification and express SEQ ID NO: 30,31,32 or 33 without defining what means will do is not in compliance with the description requirement. Rather, it is an attempt to preempt the future before it has arrived. Therefore, the concept lacks written description.
Response to arguments
Applicants’ arguments are the same as those in section A) above and are not persuasive for reasons set forth above.
Enablement
Claims 35-37, 39 remain 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 a transgenic non-human mammal whose genome comprises a genetically modified myostatin gene comprising a deletion of 12 nucleotides in exon 2 encoding the amino acid sequence leucine, tryptophan, isoleucine, and tyrosine (LWIY), does not reasonably provide enablement for any species of non-human animal, a modified myostatin gene other than one in the genome comprising a genetically modified myostatin gene comprising a deletion of 12 nucleotides in exon 2 encoding the amino acid sequence LWIY. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make/use the invention commensurate in scope with these claims.
A) The specification does not enable making/using any transgenic non-human mammal whose genome comprises a “genetically modified myostatin gene in which 12 consecutive nucleotides encoding [ ] leucine, tryptophan, isoleucine, and tyrosine (LWIY) have been deleted from exon 2” that expresses a “pro-myostatin protein consisting of the amino acid sequence of SEQ ID NO: 30, 31, 32, or 33, wherein muscle mass of the non-human mammal is higher than a wild-type non-human mammal” as required in claim 35.
Claim 35 is recited above.
The specification does not enable making any “genetically modified myostatin gene in which 12 consecutive nucleotides encoding [ ] leucine, tryptophan, isoleucine, and tyrosine (LWIY) have been deleted from exon 2” in any non-human mammal as required in claim 35. The claim requires knowledge of the sequence of the myostatin gene in any species of myostatin gene in any elephant, gazelle, deer, antelope, elk, whale, dolphin, tiger, leopard, cheetah, dingo, wolf, beaver, mole, vole, otter, et al. The claim encompasses genetically modifying the myostatin gene of any elephant, gazelle, deer, antelope, elk, whale, dolphin, tiger, leopard, cheetah, dingo, wolf, beaver, mole, vole, otter, et al. The claim encompasses obtaining a genetically modified elephant, gazelle, deer, antelope, elk, whale, dolphin, tiger, leopard, cheetah, dingo, wolf, beaver, mole, vole, otter, et al. The claim encompasses modifying the muscle mass in any genetically modified elephant, gazelle, deer, antelope, elk, whale, dolphin, tiger, leopard, cheetah, dingo, wolf, beaver, mole, vole, otter, et al.
Pg 11, para 104, teaches: “In the present application, term ‘a conserved region of the myostatin gene by species’ includes nucleic acid sequences encoding 20 amino acids in the order of leucine, tryptophan, isoleucine, and tyrosine in conserved region of the myostatin (see Table 3).” Table 3 (pg 27) shows:
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But Table 3 and the specification and the art at the time of filing as a whole do not teach any specific non-mammalian myostatin gene sequences with the combination of 12 consecutive nucleotides encoding LWIY as required in claim 35. The specification does not teach the myostatin gene in any elephant, gazelle, deer, antelope, elk, whale, dolphin, tiger, leopard, cheetah, dingo, wolf, beaver, mole, vole, otter, et al. contains LWIY as encompassed by claim 35, nor does the specification teach deleting it in those species.
Crawford (WO 2008033042) is described above.
The teachings in the specification and the Examples are described above.
The specification is limited to a genetically modified cattle whose genome comprised a mutant myostatin gene, wherein the cattle exhibited increased muscle mass as compared to a wild-type cattle (Examples 1-11). sgRNAs were created to target exon 2 of an endogenous myostatin gene and make a 12 nucleotide deletion encoding leucine, tryptophan, isoleucine, and tyrosine (LWIY) (pg 3, lines 19-25; pg 9, lines 3-6; Fig. 4, SEQ ID NO: 7 that is -12 bp). Amino acids 156-159 of bovine or pig myostatin are LWIY; amino acids 157-159 of mouse myostatin are LWIY (pg 27, Table 3). The target sequence may be any of the nucleic acid sequences of SEQ ID NO: 38-60 (pg 28, para 249, through pg 30, para 256; Table 4).
The Examples do not teach the phenotype of the cattle obtained. Therefore, the specification does not enable making any non-human mammal with the myostatin genetic modification that expresses SEQ ID NO: 30, 31, 32, or 33 and has increased muscle mass as required in claim 35.
The specification does not enable making any species of non-human mammal that expresses a pro-myostatin that is no more or less than the amino acid sequence of SEQ ID NO: 30, 31, 32, or 33. The breadth of non-human mammals is discussed above. However, the SEQ ID NO: 30 is limited to a bovine myostatin protein, SEQ ID NO: 31 is a pig protein, SEQ ID NO: 32 is a mouse protein, and SEQ ID NO: 33 is a human protein (pg 19, para 176-179). The specification does not teach or infer expressing the mutated bovine myostatin protein of SEQ ID NO: 30 in any non-bovine non-human mammal as broadly encompassed by claim 35. The specification does not teach or infer expressing the mutated pig myostatin protein of SEQ ID NO: 30 in any non-pig non-human mammal as broadly encompassed by claim 35. The specification does not teach or infer expressing the mutated mouse myostatin protein of SEQ ID NO: 30 in any non-mouse non-human mammal as broadly encompassed by claim 35. The specification does not teach or infer expressing the mutated human myostatin protein of SEQ ID NO: 30 in any non-human mammal as broadly encompassed by claim 35. The specification does not teach SEQ ID NO: 30-33 are interchangeable and would work in any species from which they were foreign. The specification does not teach SEQ ID NO: 30-33 share significant homology that would allow them to function in any non-human mammal.
Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to make/use the transgenic non-human mammal required in claim 35.
Response to arguments
Applicants point to para 162 (pg 17). Applicants’ argument is not persuasive. The paragraph does not teach any specific myostatin sequence in any non-mammalian species that encodes LWIY in exon 2. The paragraph does not contemplate deleting LWIY in exon 2.
Applicants point to para 175-179 and 199. Applicants’ argument is not persuasive. Para 175 says the animal expresses SEQ ID NO: 30, 31, 32, or 33. The paragraph does not contemplate expressing SEQ ID NO: 30, 31, 32, or 33 in non-bovine non-human mammals as encompassed by claim 35. The paragraph does not teach any specific myostatin sequence in any non-mammalian species that encodes LWIY in exon 2. The paragraph does not contemplate deleting LWIY in exon 2 as required in claim 35.
Para 176 says the animal is a bovine and the protein is SEQ ID NO: 30 “in which 4 amino acids are deleted” (this appears to be a translation error because SEQ ID NO: 30 already has 4 amino acids deleted). The paragraph is lacking the items cited above.
Para 177 says the animal is a pig and the protein is SEQ ID NO: 31 “in which 4 amino acids are deleted” (this appears to be a translation error because SEQ ID NO: 30 already has 4 amino acids deleted). The paragraph is lacking the items cited above.
Paragraphs 178, 179 contemplate mouse and human mutant myostatin proteins but are flawed for reasons set forth above.
Para 199 (pg 23) says the animal has 1-40% more muscle mass. Applicants’ argument is not persuasive for reasons set forth above.
Applicants conclude the claims are enabled because they are commensurate in scope with the specification. Applicants’ argument is not persuasive. The question is not whether the specification contemplated the scope. The question is whether the scope is enabled. The specification does not disclose the sequences, reagents, and final products required to make/use any of the non-human mammals claimed for reasons set forth above.
B) The specification does not enable obtaining “myostatin mRNA expression” in the transgenic animal being “less than that of a wild-type animal” as required in claim 36. The concept cannot be found in the specification or any of the examples. It is unclear how/why the transgenic animal would have less mRNA expression than a wild-type animal because the transgenic animal still expresses mutant myostatin mRNA and uses the same cell machinery to do so as compared to a wild-type animal. While the mRNA may encode mutant myostatin in a transgenic animal, the amount of mRNA MUST be the same as in a wild-type animal because the cell machinery is the same. Accordingly claim 36 lacks written description.
Response to arguments
Applicants argue paragraphs 28, 42, 166-169, 459-461 and Fig. 14 contemplate low myostatin mRNA expression. Applicants’ argument is not persuasive. Fig. 14 is limited to low mature myostatin mRNA expression in cattle 14 and 17 (pg 10, para 90); however, the claims are not.
C) The specification does not enable an engineered non-human mammalian cell whose genome comprises a “genetically modified myostatin gene in which 12 consecutive nucleotides encoding [ ] leucine, tryptophan, isoleucine, and tyrosine (LWIY) have been deleted from exon 2” that expresses a “pro-myostatin protein consisting of the amino acid sequence of SEQ ID NO: 30, 31, 32, or 33” as required in claim 39.
The specification does not enable making any “genetically modified myostatin gene in which 12 consecutive nucleotides encoding [ ] leucine, tryptophan, isoleucine, and tyrosine (LWIY) have been deleted from exon 2” in any non-human mammal as required in claim 39 for reasons set forth in claim 35.
Pg 11, para 104, teaches: “In the present application, term ‘a conserved region of the myostatin gene by species’ includes nucleic acid sequences encoding 20 amino acids in the order of leucine, tryptophan, isoleucine, and tyrosine in conserved region of the myostatin (see Table 3).” Table 3 (pg 27) shows:
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But Table 3 and the specification and the art at the time of filing as a whole do not teach any specific non-mammalian myostatin gene sequences with the combination of 12 consecutive nucleotides encoding LWIY as required in claim 39. The specification does not teach the myostatin gene in any elephant, gazelle, deer, antelope, elk, whale, dolphin, tiger, leopard, cheetah, dingo, wolf, beaver, mole, vole, otter, et al. contains LWIY as encompassed by claim 39, nor does the specification teach deleting it in those species.
Crawford (WO 2008033042) is described above.
The teachings of the specification and the examples are described above. The specification is limited to a genetically modified cattle whose genome comprised a mutant myostatin gene, wherein the cattle exhibited increased muscle mass as compared to a wild-type cattle (Examples 1-11). sgRNAs were created to target exon 2 of an endogenous myostatin gene and make a 12 nucleotide deletion encoding leucine, tryptophan, isoleucine, and tyrosine (LWIY) (pg 3, lines 19-25; pg 9, lines 3-6; Fig. 4, SEQ ID NO: 7 that is -12 bp). Amino acids 156-159 of bovine or pig myostatin are LWIY; amino acids 157-159 of mouse myostatin are LWIY (pg 27, Table 3). The target sequence may be any of the nucleic acid sequences of SEQ ID NO: 38-60 (pg 28, para 249, through pg 30, para 256; Table 4).
The specification does not enable making/using any species of non-human mammal cell that expresses a pro-myostatin that is no more or less than the amino acid sequence of SEQ ID NO: 30, 31, 32, or 33. The breadth of non-human mammals is discussed above. However, the SEQ ID NO: 30 is limited to a bovine myostatin protein, SEQ ID NO: 31 is a pig protein, SEQ ID NO: 32 is a mouse protein, and SEQ ID NO: 33 is a human protein (pg 19, para 176-179). The specification does not teach or infer expressing the mutated bovine myostatin protein of SEQ ID NO: 30 in any non-bovine non-human mammal as broadly encompassed by claim 39. The specification does not teach or infer expressing the mutated pig myostatin protein of SEQ ID NO: 30 in any non-pig non-human mammal as broadly encompassed by claim 39. The specification does not teach or infer expressing the mutated mouse myostatin protein of SEQ ID NO: 30 in any non-mouse non-human mammal as broadly encompassed by claim 39. The specification does not teach or infer expressing the mutated human myostatin protein of SEQ ID NO: 30 in any non-human mammal as broadly encompassed by claim 39. The specification does not teach SEQ ID NO: 30-33 are interchangeable and would work in any species from which they were foreign. The specification does not teach SEQ ID NO: 30-33 share significant homology that would allow them to function in any non-human mammal.
Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to make/use the non-human mammal cell of claim 39.
Response to arguments
Applicants’ arguments are the same as those in section A) above and are not persuasive for reasons set forth above.
Indefiniteness
The rejection of claim 37 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite has been withdrawn in view of the amendment.
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 (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 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, 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 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 35, 37-39 are rejected under 35 U.S.C. 103 as being unpatentable over XM_061432883.1 and NP_001277896.1 in view of Crawford (WO 2008033042).
XM_061432883.1 encodes NP_001277896.1 is identical to SEQ ID NO: 30 except for a 4 amino acid deletion at positions 153-156:
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394
488
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390
470
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XM_061432883.1 did not teach making a deletion in exon 2 of the myostatin gene of a non-human mammal as required in claim 35.
However, making a non-human mammal with a deletion in exon 2 of the myostatin gene such that increased muscle mass was obtained was well known in the art as described by Crawford (pg 24, lines 5-11). Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to delete amino acids LWIY from the MSTN gene to obtain a double muscle phenotype (pg 24, lines 12-17) to obtain more meat product. This is equivalent to claim 35.
Claim 37 has been included Crawford taught the mammal was a bovine.
Claim 39 has been included because the bovine is made of cells expressing a protein that consists of the amino acid sequence of SEQ ID NO: 30.
Response to arguments
Applicants argue the combined references did not teach deleting nucleotides that encode LWIY from the myostatin gene. Applicants’ argument is not persuasive. It would have been obvious to those of ordinary skill in the art at the time of filing to delete amino acids LWIY from the MSTN gene to obtain a double muscle phenotype (pg 24, lines 12-17) to obtain more meat product.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Inquiry concerning this communication or earlier communications from the examiner should be directed to Michael C. Wilson who can normally be reached at the office on Monday through Friday from 9:30 am to 6:00 pm at 571-272-0738.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638
Prosecution Insights