DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse of invention Group I (claims 83-88, 92, and 102, drawn to a composition comprising a recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) protein comprising an amino acid sequence having at least about 97% identity with SEQ ID NO: 1 or SEQ ID NO: 2 and having a substitution or deletion at position N37, E38 and/or T39 or a position corresponding thereto) in the reply filed on
2/3/2026 is acknowledged.
3. Claims 89-101 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as
being drawn to a nonelected species, there being no allowable generic or linking claim. Election
was made without traverse in the reply filed on 2/3/2026. The amendments filed 2/3/2026
are acknowledged. Claims 89-101 are withdrawn. Claims 83-88, 92, and 102 are pending and under examination.
Information Disclosure Statement
4. The information disclosure statement (IDS) submitted 4/21/23, 6/16/23, 10/1/2024, and 12/12/2025 and the references cited therein have been considered, unless indicated otherwise.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
5. Claims 83 and 102 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 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
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, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, 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 Applicants were in possession of the claimed genus.
The instant claims are drawn to a composition comprising a recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) protein, comprising an amino acid sequence having at least about 97% identity with SEQ ID NO: 1 or SEQ ID NO: 2 and having a substitution or deletion at position N37, E38 and/or T39 or a position corresponding thereto.
The specification discloses a recombinant human GM-CSF comprising SEQ ID NO:1 and SEQ ID NO: 2.
The main issue is the use of the term “an” when describing the amino acid sequences, for example in claim 1 “comprising an amino acid sequence having at least about 97% identity with SEQ ID NO: 1 or SEQ ID NO: 2.” It is also possible, given the language of the claim which includes "an amino acid sequence", that any two amino acids in sequence would suffice to meet the limitations of the claims. Because function of protein is dependent on the presence of each specific amino acid residue, and with the possibility of added or deleted amino acids, a wide variety of polypeptides, is encompassed by the instant claim. In addition, the phrase “an amino acid sequence” allows any fragment, including any two amino acids in sequence, to be encompassed in the instant claim. This would in theory encompass any possible peptide. These peptides have no correlation between their structure and function. It is recommended that Applicant amend the language of the claim to recite “comprising the amino acid sequence” in all places that “an amino acid sequence” appears to overcome this issue.
Accordingly, the specification does not define any structural features commonly possessed by the members of the genus, because, while the description of an ability of the claimed protein may generically describe the protein’s function, it does not describe the protein itself. A definition by function does not suffice to define the genu because it is only an indication of what the protein does, rather than what it is; therefore, it is only a definition of a useful result rather than a definition of what achieves the result. In addition, because the genus of GM-CSF protein is highly variable (i.e., each complex would necessarily have a unique structure, See MPEP 2434), the generic description of the heterodimer is insufficient to describe the genus. Further, given the highly diverse nature of proteins, even one of skill in the art cannot envision the structure of the GM-CSF protein only by knowing its functional characteristics. Thus, the specification does not provide substantive evidence for possession of this large and variable genus, encompassing a potentially massive number of GM-CSF protein claimed only by a functional characteristic and/or partial structure.
A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not sufficient identifying characteristics for written description purposes, even when accompanied by a method of obtaining the agent. The specification does not adequately describe the correlation between the chemical structure and function of the genus, such as structural domains or motifs that are essential and distinguish members of the genus from those excluded. Thus, the genus of protein has no correlation between their structure and function.
Furthermore, Applicants have not shown possession of a representative number of species that have the claimed function(s). The claims generically recite a GM-CSF protein. As noted above, the claims are not limited to the disclosed GM-CSF protein comprising SEQ ID NO: 1 and SEQ ID NO: 2 and broadly encompass GM-CSF protein comprising variants and fragments of SEQ ID NO: 1 and SEQ ID NO: 2. Thus, the genus has substantial variation because of the numerous alternatives and combinations permitted. There is no description of the structure common to the members of the genus such that one of skill in the art can visualize or recognize the members of the genus. Therefore, only a single species has been described and this is not considered to be representative of the breadth of the genus.
MPEP §2163 states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. If the genus has a substantial variance (as in the instant case), the disclosure must describe a sufficient variety of species to reflect the variation within that genus. Although the MPEP does not define what constitutes a sufficient number of representative species, the courts have indicated what does not constitute a representative number to adequately describe a broad genus. The courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus (e.g., see In re Gostelli, 872, F. 2d at 1012, 10 USPQ2d at 1618).
Further, the disclosure of only one or two 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 genu[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.") (MPEP 2163). “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).
Accordingly, the specification also does not provide adequate written description to identify the broad genus of the claimed, claimed only be a function characteristic(s) and not structures per se, because inter alia, it does not describe a sufficient number and/or a sufficient variety of representative species to reflect the breadth and variation within the claimed genus. Consequently, based on the lack of information within the specification, there is evidence that a representative number and a representative variety of the numerous heterodimers had not yet been identified and thus, the specification represents little more than a wish for possession. Therefore, one of skill in the art would not conclude that Applicant was in possession of the broad and highly variable genus of heterodimers claimed only by a partial structure and functional characteristic(s).
Vas-Cath Inc. v. Mahurkar, 19 U5PQ2d 1111, makes clear that
"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. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.)The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
With the exception of a GM-CSF protein comprising SEQ ID NO:1 and SEQ ID NO:2, the skilled artisan cannot envision the detailed chemical structure of the encompassed polypeptides, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The nucleic acid and/or protein itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481,1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc., 107 F.3d 1565,1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d 1966.
In Ariad Pharrns., Inc. v. Eh Lilly & Co., 598 F.3d 1336,1351 (Fed. Cir. 2010), the court held that a “sufficient description of a genus ... requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize’ the members of the genus." Ariad, 598 F.Bd at 1350. “[A]n adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials,” Id. Although “functional claim language can meet the written description requirement when the art has established a correlation between structure and function," "merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genu and showing that one has invented a genus and not just a species.
Furthermore, regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods. Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004).
Protein chemistry is probably one of the most unpredictable areas of biotechnology. Consequently, the effects of sequence dissimilarities upon protein structure and function cannot be predicted. Bowie et al. (Science, 1990, 247:1306-1310) teach that an amino acid sequence encodes a message that determines the shape and function of a protein and that it is the ability of these proteins to fold into unique three-dimensional structures that allows them to function and carry out the instructions of the genome and further teaches that the problem of predicting protein structure from sequence data and in turn utilizing predicted structural determinations to ascertain functional aspects of the protein is extremely complex (column 1, page 1306). Bowie et al. further teach that while it is known that many amino acid substitutions are possible in any given protein, the position within the protein's sequence where such amino acid substitutions can be made with a reasonable expectation of maintaining function are limited. Certain positions in the sequence are critical to the three dimensional structure/function relationship and these regions can tolerate only conservative substitutions or no substitutions at all (column 2, page 1306). The sensitivity of proteins to alterations of even a single amino acid in a sequence are exemplified by Burgess et al. (J. Cell Biol. 111:2129-2138,1990) who teach that replacement of a single lysine residue at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein and by Lazar et al. (Mol. Cell. Biol., 8:1247-1252,1988) who teach that in transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen. These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of a protein.
Additionally, Whisstock et al. (Quarterly Reviews in Biophysics. 36(3):307-340, 2007) teach that the prediction of protein function from sequence and structure is a difficult problem (See abstract). Although many families of proteins contain homologues with the same function, homologous proteins often have different functions as the sequences progressively diverge (See page 309). Whisstock et al. teach that assigning a function to an amino acid sequence based upon similarity becomes significantly more complex as the similarity between the sequence and a putative homologue falls. Whisstock et al. teach that while it is hopeful that similar proteins will share similar functions, substitution of a single, critically placed amino acid in an active-site may be sufficient to alter a protein’s role fundamentally (See pages 321-323). Given not only the teachings of Bowie et al., Lazar et al. and Burgess et al. but also the limitations and pitfalls of assigning a function to an amino acid sequence based upon similarity as taught by Whisstock, the claimed proteins could not be predicted. Therefore, the state of the art supports that even the skilled artisan requires guidance on the critical structures of the agent per se and thereby does not provide adequate written description support for which structural features of any given polypeptide would predictably retain their functional activities.
Accordingly, one of skill in the art would conclude that the claimed invention encompasses a plurality of polypeptides defined solely in terms of their function that may not have the biological functions recited in the claims. Based on the teachings of the instant specification and the prior art, one of skill in the art would not conclude that Applicant was in possession of the claimed genus of agents.
While “examples explicitly covering the full scope of the claim language” typically will not be required, a sufficient number of representative species must be included to “demonstrate that the patentee possessed the full scope of the [claimed] invention.” Lizardtech v. Earth Resource Mapping, Inc., 424 F.3d 1336, 1345, 76 USPQ2d 1724, 1732 (Fed. Cir. 2005).
In the absence of sufficient recitation of distinguishing characteristics, the specification does not provide adequate written description of the claimed genus. One of skill in the art would not recognize from the disclosure that the applicant was in possession of the genus. 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, Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1895 (Fed. Cir. 2004); accord Ex Parte Kubin, 2007-0819, BPAI 31 May 2007, opinion at p. 16, paragraph 1). The specification does not clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed (see Vas-Cath at page 1116).
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision (see page 1115).
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.
6. Claim 83 and 102 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “…comprising an amino acid sequence having at least about 97% identity with SEQ ID NO: 1 or SEQ ID NO: 2.”.” The use of “an amino acid sequence” encompasses amino acids that comprise the full-length sequence of SEQ ID NO: 1 and 2 or any portion of SEQ ID NO: 1 and 2. Given the broadest reasonable interpretation, the claimed method would encompass administering the full-length amino acid sequence set forth in SEQ ID NO: 1 and 2 or any portion of SEQ ID NO: 1 and 2. However, the specification provides no guidance regarding the specific portion(s) of SEQ ID NO: 1 and 2 that would maintain the GM-CSF protein function. Thus, there is ambiguity as to the scope of the claim and one of skill in the art would not be apprised of the scope of the claim. Clarification and/or correction is required.
It is suggested that Applicant amend the claim as follows for clarity and precision of claim language: A composition comprising a recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) protein, comprising the amino acid sequence having at least about 97% identity with SEQ ID NO: 1 or SEQ ID NO: 2 and having a substitution or deletion at position N37, E38 and/or T39 or a position corresponding thereto
7. The term “at least” in claims 83 and 102 is a relative term which renders the
claim indefinite. The term “at least” 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. The word at least introduces a
range of possibilities and even wider in some interpretations which causes ambiguity. The
rationale for avoiding such phrasing comes down to accuracy, reproducibility and the proper
representation of uncertainty.
8. The term “substantially” in claims 86 and 88 and “substantial” in claims 88 and 102 is a relative term which renders the claim indefinite. The term “substantially” and ”substantial” 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. The word at least introduces a range of possibilities and even wider in some interpretations which causes ambiguity. The rationale for avoiding such phrasing comes down to accuracy, reproducibility and the proper representation of uncertainty.
Claim Rejections - 35 USC § 102
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.
9. Claim 83 and 87-88 is rejected under 35 U.S.C 102(a)(2) as being unpatentable over Gantier, et al. (U.S. Publication No: US 2004/0132977 A1), issues July 8, 2004).
Instant claim 83 and 84 teach a composition comprising a recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) protein, comprising an amino acid sequence having at least about 97% identity with SEQ ID NO: 1 or SEQ ID NO: 2 and having a substitution or deletion at position N37, E38 and/or T39 or a position corresponding thereto.
Gantier, et al. teach a modified human granulocyte macrophage colony stimulating factor cytokine comprising as amino acid sequences corresponding to SEQ ID NO: 362, 363, 364 which are at least about 97% identity with instant SEQ ID NO 1 and 2, and have a substitution at the position E38.
Gantier, et al. SEQ ID NO: 362 is at least about 97% match to instant SEQ ID NO: 1 with substitution at the E38 position.
Query Match 99.6%; Score 670; Length 127;
Best Local Similarity 99.2%;
Matches 126; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE 60
|||||||||||||||||||||||||||||||||||||:||||||||||||||||||||||
Db 1 APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNQTVEVISEMFDLQEPTCLQTRLE 60
Qy 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
Qy 121 CWEPVQE 127
|||||||
Db 121 CWEPVQE 127
Gantier, et al. SEQ ID NO: 363 is at least about 97% match to instant SEQ ID NO: 1 with substitution at the E38 position.
Query Match 99.3%; Score 668; Length 127;
Best Local Similarity 99.2%;
Matches 126; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE 60
||||||||||||||||||||||||||||||||||||| ||||||||||||||||||||||
Db 1 APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNNTVEVISEMFDLQEPTCLQTRLE 60
Qy 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
Qy 121 CWEPVQE 127
|||||||
Db 121 CWEPVQE 127
Gantier, et al. SEQ ID NO: 364 is at least about 97% match to instant SEQ ID NO: 1 with substitution at the E38 position.
Query Match 99.3%; Score 668; Length 127;
Best Local Similarity 99.2%;
Matches 126; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE 60
||||||||||||||||||||||||||||||||||||| ||||||||||||||||||||||
Db 1 APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNHTVEVISEMFDLQEPTCLQTRLE 60
Qy 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
Qy 121 CWEPVQE 127
|||||||
Db 121 CWEPVQE 127
Gantier, et al. SEQ ID NO: 362 is at least about 97% match to instant SEQ ID NO: 2 with substitution at the E38 position.
Query Match 98.7%; Score 663; Length 127;
Best Local Similarity 98.4%;
Matches 125; Conservative 1; Mismatches 1; Indels 0; Gaps 0;
Qy 1 APARSPSPSTQPWEHVNAIQEALRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE 60
|||||||||||||||||||||| ||||||||||||||:||||||||||||||||||||||
Db 1 APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNQTVEVISEMFDLQEPTCLQTRLE 60
Qy 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
Qy 121 CWEPVQE 127
|||||||
Db 121 CWEPVQE 127
Gantier, et al. SEQ ID NO: 363 is at least about 97% match to instant SEQ ID NO: 2 with substitution at the E38 position.
Query Match 98.4%; Score 661; Length 127;
Best Local Similarity 98.4%;
Matches 125; Conservative 0; Mismatches 2; Indels 0; Gaps 0;
Qy 1 APARSPSPSTQPWEHVNAIQEALRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE 60
|||||||||||||||||||||| |||||||||||||| ||||||||||||||||||||||
Db 1 APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNNTVEVISEMFDLQEPTCLQTRLE 60
Qy 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
Qy 121 CWEPVQE 127
|||||||
Db 121 CWEPVQE 127
Instant claim 87 teach the composition of claim 83, wherein the recombinant human GM-CSF comprises a plurality of molecular forms selected from non-glycosylated, 0-glycosylated, N-glycosylated and N+0 glycosylated forms. Gantier, et al. teach N-glycosylation sites can be added to increase resistance to proteolysis while maintaining or improving requires biological activity (paragraph 293). This anticipates instant claim 87.
Instant claim 88 recites the composition of claim 83, wherein (a) the recombinant human GM-CSF is substantially free of hypermannosylated forms, (b) the recombinant human GM-CSF resolves as three peaks when quantified by reversed phase high- performance liquid chromatography (RP-HPLC), (c) the recombinant human GM-CSF provides no substantial peaks at a retention time of less than about 20 minutes when quantified by reversed phase high-performance liquid chromatography (RP- HPLC), and/or (d) the recombinant human GM-CSF is substantially free of hypermannosylated forms when purified without the use of organic solvents, or without the use of a reversed phase C4 HPLC column. Instant claim 88 is interpreted as a product by process claim. It is noted that product by process claims are not limited to the manipulation of the recited steps, but only the structure implied by those steps (see MPEP 2113). MPEP 2113 states that “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). Furthermore, "[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes." Amgen Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340, 1370 n 14, 92 USPQ2d 1289, 1312, n 14 (Fed. Cir. 2009). However, in the context of an infringement analysis, a product-by-process claim is only infringed by a product made by the process recited in the claim. Id. at 1370 ( "a product in the prior art made by a different process can anticipate a product-by-process claim, but an accused product made by a different process cannot infringe a product-by-process claim." ). Thus, the product of the Gantier, et al. anticipate the product of the instant claims, even if made by a different process.
Double Patenting
10. 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 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
11. Claims 83-86, and 92 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 114 and 115 of copending Application No. 18854328.
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims recite a recombinant human granulocyte macrophage colony stimulating factor protein.
Instant claim 83 directs to a composition comprising a recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) protein, comprising an amino acid sequence having at least about 97% identity with SEQ ID NO: 1 or SEQ ID NO: 2 and having a substitution or deletion at position N37, E38 and/or T39 or a position corresponding thereto. Instant claim 84 further limits the recombinant human (GM-CSF) protein amino sequence wherein (a) the amino acid at position N37 or a position corresponding thereto is selected from glutamine (Q),serine (S), threonine (T), proline (P), and cysteine (C); (b) the amino acid at T39 or a position corresponding thereto is selected from alanine (A), glycine (G), leucine (L), isoleucine (I), methionine (M), and valine (V), and alanine (A); or (c) the amino acid at position E38 or a position corresponding thereto is selected from alanine (A), leucine (L), isoleucine (I), methionine (M), and valine (V).
Claim 114 of copending application ‘328 direct to a composition comprising a fusion or chimeric protein comprising a recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) protein, as well as a linker and single domain antibody. Claim 115 of copending application ‘328 further limits the recombinant human GM-CSF protein amino acid sequence wherein the recombinant human GM-CSF protein comprises an amino acid sequence: having at least 97% identity to the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or having at least 97% identity to the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2 and a substitution or deletion at position asparagine (N) 37 or a position corresponding thereto, wherein the substitution is selected from glutamine (Q), serine (S), and threonine (T). Instant SEQ ID NO: 1 and 2 are 100% identical to copending application ‘328 SEQ ID NO: 1 and 2. The substitution and deletions requirements of the amino acid sequence required by the instant claims are anticipated by the copending application claims.
Copending application ‘328 SEQ ID NO: 1 is 100% match with instant SEQ ID NO: 1
RESULT 1
US-18-854-328-1
Query Match 100.0%; Score 673; DB 1; Length 127;
Best Local Similarity 100.0%;
Matches 127; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE 60
Qy 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
Qy 121 CWEPVQE 127
|||||||
Db 121 CWEPVQE 127
Copending application ‘328 SEQ ID NO: 2 is 100% match with instant SEQ ID NO: 2
RESULT 1
US-18-854-328-2
Query Match 100.0%; Score 672; DB 1; Length 127;
Best Local Similarity 100.0%;
Matches 127; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APARSPSPSTQPWEHVNAIQEALRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 APARSPSPSTQPWEHVNAIQEALRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE 60
Qy 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
Qy 121 CWEPVQE 127
|||||||
Db 121 CWEPVQE 127
Instant claim 85 teach the composition of claim 83, wherein the composition binds and/or activates the granulocyte- macrophage colony stimulating factor receptor (GM-CSF-R-alpha or CSF2R), wherein the GM-CSF-R-alpha is expressed on the surface of a cell selected from a hematopoietic progenitor cell, and wherein the hematopoietic progenitor cell is an immune cell, and/or is irradiated. Copending application ‘328 teach modulating hematopoietic progenitor cells and/or stimulating survival, proliferation and activation of neutrophils, macrophages and/or dendritic cells in a subject in need thereof, comprising administering an effective amount of the pharmaceutical composition of claim 134 to the subject, wherein the subject: is undertaking or has undertaken a cancer therapy, is undertaking or has undertaken a bone marrow transplant, has been acutely exposed to myelosuppressive doses of radiation, or has a Radiation Combined Injury (RCI). This recites the limits of instant claim 85.
Instant claim 86 teach the recombinant human GM-CSF is soluble and has substantially similar function as sargramostim. Copending application ‘328 teach the composition of claim 114, wherein the fusion or chimeric protein demonstrates enhanced pharmacokinetics as compared to sargramostim.
Instant claim 92 teach a pharmaceutical composition comprising a recombinant human GM-CSF of claim 83 and a pharmaceutically acceptable excipient or carrier. Copending application ‘328 teach a pharmaceutical composition comprising a composition of claim 114 and a pharmaceutically acceptable excipient or carrier (claim 133), which contains the recombinant human GM-CSF of instant claim 92.
Conclusion
12. No claims are allowed.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Syed J Abbas whose telephone number is (571)272-0015. The examiner can normally be reached M-Th, 9:00AM-4:00PM.
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, Vanessa Ford can be reached at 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SYED J ABBAS/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674