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 .
1. Claims 1-11 as filed on February 12, 2024 are pending and under consideration.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
2. Claims 1, 6, 7, and 9-11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more. The claim(s) recite(s) an isolated or recombinantly produced peptidase D (PEPD) or mutated forms thereof. This judicial exception is not integrated into a practical application because the recitation of “[a] pharmaceutical preparation for use in prophylaxis and/or therapy of ErbB2 positive cancer” and “an indication that the pharmaceutical preparation is for use with a coagulation inhibitor” are intended uses that do not change the structure or function of PEPD. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because pharmaceutically acceptable carriers, containers and instructions for use are routine in the art and do not change the structure or function of PEPD.
The Mayo framework provides that first whether the claims at issue are directed to a patent-ineligible concept is determined. If the answer is yes, then the elements of each claim both individually and “as an ordered combination” are considered to determine whether additional elements “transform the nature of the claim” into a patent-eligible application. The second step—known as the “inventive concept”—requires that claims include elements which would render the method both new and useful.
The recent Eligibility Guidance (2014 Interim Guidance on Patent Subject Matter Eligibility (Interim Eligibility Guidance and 2018 Revised Patent Subject Matter Eligibility Guidance published in the Federal Register (84 FR 50) on January 7, 2019) address the subject matter eligibility analysis for all claims (i.e., machine, composition of matter, manufacture and process claims). The analysis is to be used for evaluating whether a claim is drawn to patent-eligible subject matter.
Step 1 determines whether the claim is directed to a process, machine, manufacture, or composition of matter. If the claim is directed to a statutory category, proceed to Step 2.
Step 2 is the two-part analysis for claims directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions).
In Step 2A, determine whether the claim is directed to a law of nature, a natural phenomenon, or an abstract idea (judicial exceptions). “Directed to” means the exception is recited in the claim, i.e., the claim sets forth or describes the exception.
In Prong One of Step 2A it is determined if the claim recites a judicial exception. If the claim recites a judicial exception then Prong Two of Step 2A determines whether the claims recites additional elements that integrate the exception into a practical application.
If the answer to Prong Two of Step 2A is no, Step 2B is used to determine whether the claim as a whole amounts to significantly more than the exception by the recitation of additional elements.
The present claims are directed to a product so Step 1 is satisfied.
With respect to Step 2A MPEP 2106.04(c) II(C)(2) teaches:
In Myriad, the Supreme Court made clear that not all changes in characteristics will rise to the level of a marked difference, e.g., the incidental changes resulting from isolation of a gene sequence are not enough to make the isolated gene markedly different. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. The patentee in Myriad had discovered the location of the BRCA1 and BRCA2 genes in the human genome, and isolated them, i.e., separated those specific genes from the rest of the chromosome on which they exist in nature. As a result of their isolation, the isolated genes had a different structural characteristic than the natural genes, i.e., the natural genes had covalent bonds on their ends that connected them to the rest of the chromosome, but the isolated genes lacked these bonds. However, the claimed genes were otherwise structurally identical to the natural genes, e.g., they had the same genetic structure and nucleotide sequence as the BRCA genes in nature. The Supreme Court concluded that these isolated but otherwise unchanged genes were not eligible, because they were not different enough from what exists in nature to avoid improperly tying up the future use and study of the naturally occurring BRCA genes. See, e.g., Myriad, 569 U.S. at 585, 106 USPQ2d at 1977 ("Myriad's patents would, if valid, give it the exclusive right to isolate an individual’s BRCA1 and BRCA2 genes … But isolation is necessary to conduct genetic testing") and 569 U.S. at 593, 106 USPQ2d at 1980 (describing how would-be infringers could not avoid the scope of Myriad’s claims). In sum, the claimed genes were different, but not markedly different, from their naturally occurring counterparts (the BRCA genes), and thus were product of nature exceptions.
In Ambry Genetics, the court identified claimed DNA fragments known as "primers" as products of nature, because they lacked markedly different characteristics. University of Utah Research Foundation v. Ambry Genetics Corp., 774 F.3d 755, 113 USPQ2d 1241 (Fed. Cir. 2014). The claimed primers were single-stranded pieces of DNA, each of which corresponded to a naturally occurring double-stranded DNA sequence in or near the BRCA genes. The patentee argued that these primers had markedly different structural characteristics from the natural DNA, because the primers were synthetically created and because "single-stranded DNA cannot be found in the human body". The court disagreed, concluding that the primers’ structural characteristics were not markedly different than the corresponding strands of DNA in nature, because the primers and their counterparts had the same genetic structure and nucleotide sequence. 774 F.3d at 760, 113 USPQ2d at 1243-44. The patentee also argued that the primers had a different function than when they are part of the DNA strand because when isolated as a primer, a primer can be used as a starting material for a DNA polymerization process. The court disagreed, because this ability to serve as a starting material is innate to DNA itself, and was not created or altered by the patentee:
In fact, the naturally occurring genetic sequences at issue here do not perform a significantly new function. Rather, the naturally occurring material is used to form the first step in a chain reaction--a function that is performed because the primer maintains the exact same nucleotide sequence as the relevant portion of the naturally occurring sequence. One of the primary functions of DNA’s structure in nature is that complementary nucleotide sequences bind to each other. It is this same function that is exploited here--the primer binds to its complementary nucleotide sequence. Thus, just as in nature, primers utilize the innate ability of DNA to bind to itself.
Ambry Genetics, 774 F.3d at 760-61, 113 USPQ2d at 1244. In sum, because the characteristics of the claimed primers were innate to naturally occurring DNA, they lacked markedly different characteristics from nature and were thus product of nature exceptions. A similar result was reached in Marden, where the court held a claim to ductile vanadium ineligible, because the "ductility or malleability of vanadium is . . . one of its inherent characteristics and not a characteristic given to it by virtue of a new combination with other materials or which characteristic is brought about by some chemical reaction or agency which changes its inherent characteristics". In re Marden, 47 F.2d 958, 959, 18 CCPA 1057, 1060, 8 USPQ 347, 349 (CCPA 1931
For Prong One of Step 2A the claims recite a judicial exception, i.e. a natural product which is a natural phenomenon. In particular, the claims recite the natural protein PEPD. Although claims 6 recites a PEPD with less dipeptide hydrolysis activity and a PEPD comprising a mutation of glycine at position 278 of SEQ ID NO: 1, these forms of PEPD occur naturally. In particular, Ledoux et al. (Am. J. Hum. Genet 59:1035-1039, 1996) teaches prolidase/PEPD mutants, including a G278D, from a prolidase deficient patient that are enzymatically inactive. See Summary and Fig. 1-3. So the answer to Prong One of Step 2A is yes the claims do recite a judicial exception.
For Prong Two of Step 2A the claims do not integrate the exception into a practical application. The judicial exception is not integrated into a practical application because the recitation of “[a] pharmaceutical preparation for use in prophylaxis and/or therapy of ErbB2 positive cancer” and “an indication that the pharmaceutical preparation is for use with a coagulation inhibitor” are intended uses or instructions that do not change the structure or function of PEPD.. So the answer to Prong Two of Step 2A is no.
With respect to Step 2B MPEP 2106.05 (I) teaches that
The second part of the Alice/Mayo test is often referred to as a search for an inventive concept. Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 217, 110 USPQ2d 1976, 1981 (2014) (citing Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 71-72, 101 USPQ2d 1961, 1966 (2012)).
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An inventive concept "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself." Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016). See also Alice Corp., 573 U.S. at 21-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 78, 101 USPQ2d at 1968 (after determining that a claim is directed to a judicial exception, "we then ask, ‘[w]hat else is there in the claims before us?") (emphasis added)); RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017) ("Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract"). Instead, an "inventive concept" is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself. Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966).
With respect to Step 2B MPEP 2106.05 (d) teaches that:
Another consideration when determining whether a claim recites significantly more than a judicial exception is whether the additional element(s) are well-understood, routine, conventional activities previously known to the industry.
If the additional element (or combination of elements) is a specific limitation other than what is well-understood, routine and conventional in the field, for instance because it is an unconventional step that confines the claim to a particular useful application of the judicial exception, then this consideration favors eligibility. If, however, the additional element (or combination of elements) is no more than well-understood, routine, conventional activities previously known to the industry, which is recited at a high level of generality, then this consideration does not favor eligibility.
. . .
On the other hand, Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 67, 101 USPQ2d 1961, 1964 (2010) provides an example of additional elements that were not an inventive concept because they were merely well-understood, routine, conventional activity previously known to the industry, which were not by themselves sufficient to transform a judicial exception into a patent eligible invention. Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 79-80, 101 USPQ2d 1969 (2012) (citing Parker v. Flook, 437 U.S. 584, 590, 198 USPQ 193, 199 (1978) (the additional elements were "well known" and, thus, did not amount to a patentable application of the mathematical formula)). In Mayo, the claims at issue recited naturally occurring correlations (the relationships between the concentration in the blood of certain thiopurine metabolites and the likelihood that a drug dosage will be ineffective or induce harmful side effects) along with additional elements including telling a doctor to measure thiopurine metabolite levels in the blood using any known process. 566 U.S. at 77-79, 101 USPQ2d at 1967-68. The Court found this additional step of measuring metabolite levels to be well-understood, routine, conventional activity already engaged in by the scientific community because scientists "routinely measured metabolites as part of their investigations into the relationships between metabolite levels and efficacy and toxicity of thiopurine compounds." 566 U.S. at 79, 101 USPQ2d at 1968. Even when considered in combination with the other additional elements, the step of measuring metabolite levels did not amount to an inventive concept, and thus the claims in Mayo were not eligible. 566 U.S. at 79-80, 101 USPQ2d at 1968-69.
Additionally MPEP 2106.05 (d) II teaches that:
The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
ii. Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
iii. Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
iv. Immunizing a patient against a disease, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011);
v. Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
vi. Freezing and thawing cells, Rapid Litig. Mgmt. 827 F.3d at 1051, 119 USPQ2d at 1375;
vii. Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014); and
viii. Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d at 1247.
The additional limitations of relate to pharmaceutically acceptable carriers, containers and instructions for use are routine in the art and do not change the structure or function of PEPD. Thus the PEPD does not have a significanly different structure or function from the naturally occuring PEPD and mutants thereof. The absence of structural differences taken together with the lack of any functional difference between the claimed PEPD and mutants and their natural counterparts demonstrates that the recited products are not markedly different from what exists in nature.
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.
3. Claim(s) 1-3, 9 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Golz et al (WO 2004/104595, Dec 2, 2004, IDS). “Golz”.
It is noted that the recitation of “[a] pharmaceutical preparation for use in prophylaxis and/or therapy of ErbB2 positive cancer” in claims 1 and 9 and “an indication that the pharmaceutical preparation is for use with a coagulation inhibitor” in claim 11 are an intended uses that do not result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art and thus is not given weight for comparison of the claims with the prior art.
Golz teaches a method of preparation of pharmaceutical composition for treating a disease including cancer, wherein the composition comprises PEPD protein or polypeptide and pharmaceutically acceptable carrier (abstract, page 86-line 20 to page-87 line 21) or a fusion protein comprising PEPD linked to a detectable agent (page 23) or fused to histidine residues or Ig Fc region tagged for purification (page 33, lines 5-20, page 116, 120).
Golz teaches the pharmaceutical composition for therapy comprising a sealed container containing PEPD and printed instructions for administration (page 91-lines 3-5 and p. 92-lines 13-28 ). The product disclosed by Golz anticipates the instantly claimed product.
Regarding claims 9 and 11, it is noted that patentable weight is not given to instructional limitations in a product claim absent a new and unobvious functional relationship between the instructional limitations and the product. See MPEP 2112.01 (III) and In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004).
4. Claim(s) 1-2, 6, 7 and 9-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ledoux et al. (Am. J. Hum. Genet 59:1035-1039, 1996), “Ledoux”.
It is noted that the recitation of “[a] pharmaceutical preparation for use in prophylaxis and/or therapy of ErbB2 positive cancer” in claims 1 and 9 and “an indication that the pharmaceutical preparation is for use with a coagulation inhibitor” in claim 11 are an intended uses that do not result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art and thus is not given weight for comparison of the claims with the prior art.
Ledoux teaches prolidase/PEPD mutants, including G278D, from a prolidase deficient patient that are enzymatically inactive. See Summary and Fig. 1-3.
Ledoux teaches prolidase/PEPD proteins were incubated a buffers containing Tris and MnCl2, i.e., pharmaceutically acceptable carrier. See p. 1036-Transient Expression of HA-Prolidase in COS-1 Cells and Prolidase Assay.
Ledoux teaches the prolidase/PEPD peptides were fused to an HA1 epitope tag. See Summary and p. 1036-Construction of the Expression Vector.
Ledoux teaches that the prolidase/PEPD peptides were expressed in COS-1 cells, harvested and immunoprecipitated with centrifugation. See p. 1036-Transient Expression of HA-Prolidase in COS-1 Cells and Prolidase Assay. One of skill in the art would immediately envision that the expression and immunoprecipitation with centrifugation of the prolidase/PEPD would require sealed containers, e.g. microcentrifuge tudes with lids.
Regarding claims 9-11, it is noted that patentable weight is not given to instructional limitations in a product claim absent a new and unobvious functional relationship between the instructional limitations and the product. See MPEP 2112.01 (III) and In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004).
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, 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.
5. Claim(s) 8 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Golz et al (WO 2004/104595, Dec 2, 2004, IDS). “Golz” as applied to claims 1-3, 9 and 11 above, and further in view of Lima et al (Biosci Rep, online published July 26, 2013, IDS), “Lima”.
Golz teaches as set forth above.
Golz does not teach the composition further comprising coagulation factor inhibitor. But, Golz does teach many blood disorders including cancers related to coagulation disorders (pages 59-61 and 77-80).
Lima teaches activation of blood coagulation in cancer in tumor progression wherein the contribution of coagulation factors including tissue factor, FVIIa, and XIIII. (entire document). Lima teaches anticancer therapy with coagulation factor inhibitor (page 705, right col).
It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art.” See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) and MPEP 2144.06.
The instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose in order to form a third composition that is to be used for the very same purpose since the idea of combining them flows logically from their having been individually taught in the prior art. Appling the same logic to the instant claims, given the teachings of the prior art, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention was made to add coagulation inhibitor in the composition to further inhibit tissue factor, FVIIa, and XIIII for cancer treatment with expected results. One of ordinary skill in the art at the time the invention was made would have been motivated with reasonable expectation of success to combine the teachings as set forth above in order to benefit cancer treatment because Golz disclosed a pharmaceutical composition comprising and method of using PEPD for treating cancer and Lima taught the role of coagulation factor in cancer condition and suggested the coagulation factor targeting therapy. Therefore, the references in combination teach every limitation of the claims and the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention was made, absent unexpected results.
6. Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Golz et al (WO 2004/104595, Dec 2, 2004, IDS). “Golz” as applied to claims 1-3, 9 and 11 above, and further in view of US 2002/0103133 A1 (Copeland et al, Aug 2002, IDS), “Copeland”.
Golz teaches as set forth above.
Golz does not teach a pharmaceutical comprising PEPD conjugated to a chemotherapeutic drug. But Golz did teach the composition being administered with a drug or agent (bridging page 88-89).
Targeting anti-cancer therapy with a conjugate comprising chemotherapy and targeting peptide or antibody has been practiced is well practiced by one skilled in the art. For example, Copeland teaches a chemotherapeutic drug conjugated to a peptide used for treating cancer and method making such conjugate (entire document, abstract, and summary).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention was made to make a PEPD conjugate with chemotherapeutic drug and used it for treating a cancer with expected result. One of ordinary skill in the art at the time the invention was made would have been motivated with reasonable expectation of success to do so in order to increase the efficacy for cancer treatment because Golz disclosed a method of using PEPD for treating cancer and Copeland have shown the method of using conjugate of chemotherapy drug linked to a peptide for cancer treatment as well as a method of making the conjugate. Therefore, the references in combination teach every limitation of the claims and the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention was made, absent unexpected results.
7. Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Golz et al (WO 2004/104595, Dec 2, 2004, IDS). “Golz” as applied to claims 1-3, 9 and 11 above, and further in view of US Pat. No. 6,395,889 (Robison, KE, May 28, 2002), “Robison”.
Golz teaches as set forth above.
Golz does not teach where the PEPD is fused to an Fc regions of immunoglobulin.
Robison teaches protease polypeptides and homologs thereof for diagnosis and treatment in protease-mediated disorders. See abstract.
Robison teaches the protease polypeptides are homologous to PEPD. See column 2-lines 50-55 and column 10-lines 60-62.
Robison teaches making fusion of the protease polypeptides the Fc domain of immunoglobulins. Robison teaches the Fc fusions are useful in therapy and diagnosis and in improved pharmacokinetic properties and can be used for the purpose of high-throughput screening assays . See col. 37-line 59 to col .38-line 12.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Golz and Robison and make Fc fusion proteins of the PEPD of Golz because Golz teaches making Fc fusion proteins of the PEPD and Robison teaches the Fc fusions are useful in therapy and diagnosis and in improved pharmacokinetic properties and can be used for the purpose of high-throughput screening assays. Thus, given the advantages of an Fc fusion protein taught by Robison, one of skill in the art would have been motivated to make an Fc fusion protein of the of the PEPD of Golz.
8. Claims 6, 7 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Golz et al (WO 2004/104595, Dec 2, 2004, IDS). “Golz” as applied to claims 1-3, 9 and 11 above, and further in view of Yang et al. (JBC Dec. 4, 2012, 288(4): 1108-119, IDS). “Yang”
Golz teaches as set forth above.
Golz teaches that PEPD proteins include PEPD analogs that have sequence mutations. See p. 34-line 25 to p. 35 line 5.
Golz teaches inhibition of the PEPD activity when the PEPD activity is abnormally high. See p. 86-lines 9-15.
Golz teaches producing transgenic animals with the PEPD activity decreased. See Example 13.
Golz does not teach where the PEPD has less dipeptide hydrolysis activity as compared to SEQ ID NO: 1 or where in the PEPD comprise a mutation of glycine at position 278 of SEQ ID NO: 1.
Yang teaches that the PEPD directly binds to and activates epidermal growth factor receptor (EGFR), leading to stimulation of signaling proteins downstream of EGFR. See abstract and Figs. 1-3.
Yang teaches the enzymatically inactive PEPD G278D is similarly effective in stimulating EGFR phosphorylation and the phosphorylation of AKT, STAT3, and ERK indicating that the enzymatic activity of PEPD is not required for EGFR activation . See p. 2370-left column.
Yang teaches that EGFR signaling may be involved in disease development of PEPD deficiency and stimulating EGFR signaling may be a therapeutic option for this disease.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Golz and Yang and use the PEPD G278D protein of Yang in the pharmaceutical compositions of Golz because Golz teaches that PEPD proteins include PEPD analogs that have sequence mutations and using PEPD proteins with decreased activity and Yang teaches that PEPD and the PEPD G278D protein directly bind to and activates EGFR and EGFR signaling may be involved in disease development of PEPD deficiency. Thus, one would have been motivated to use PEPD G278D in in the pharmaceutical compositions of Golz given its ability to activate EGFR and reduce any side effects of an active PEPD.
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.
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim not is patentably distinct from the reference claim(s) because the examined 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).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
9. Claims 1-11 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 10,478,477 (‘477) in view of Golz et al (WO 2004/104595, Dec 2, 2004, IDS). “Golz”, in view of US 2002/0103133 A1 (Copeland et al, Aug 2002, IDS), “Copeland” and in view of US Pat. No. 6,395,889 (Robison, KE, May 28, 2002), “Robison” .
The instant claims are drawn to:
A pharmaceutical composition for used in prophylaxis and/or therapy of ErbB2-positive cancer comprising a peptidase C (PEPD) and at least one pharmaceutically acceptable carrier or which comprises a mutation of G278 of SEQ ID NO:1 and has less dipeptide hydrolysis activity, wherein the composition further comprises a coagulation inhibitor and the PEPD is a fusion protein, wherein the PEPD is fused with polyhistidine tag or Fc region and chemotherapeutic agent.
The claims of U.S. Patent ‘477 are drawn to:
A method for in prophylaxis and/or therapy of ErbB2-positive cancer in an individual comprising administering the individual a composition comprising a peptidase C (PEPD) which comprises a mutation of G278 of SEQ ID NO: 1 and has less dipeptide hydrolysis activity, wherein the composition further comprises anti-coagulant and PEPD is a component of fusion protein.
The instant SEQ ID NO: 1 has the identical sequences as the sequence of SEQ ID NO: 1 of ‘477 patent as evidenced by sequence alignment:
; Sequence 1, Application US/15504560A
; Patent No. 10478477
; APPLICANT: Health Research, Inc.
; TITLE OF INVENTION: METHODS FOR PROPHYLAXIS AND/OR TREATMENT OF ERBB1 POSITIVE CANCERS
; FILE REFERENCE: 003551.00614
; CURRENT APPLICATION NUMBER: US/15/504,560A
; CURRENT FILING DATE: 2017-03-22
; PRIOR APPLICATION NUMBER: 62/039,497
; PRIOR FILING DATE: 2014-08-20
; NUMBER OF SEQ ID NOS: 13
US-15-504-560A-1
Query Match 100.0%; Score 2600; DB 1; Length 493;
Best Local Similarity 100.0%;
Matches 493; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MAAATGPSFWLGNETLKVPLALFALNRQRLCERLRKNPAVQAGSIVVLQGGEETQRYCTD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAAATGPSFWLGNETLKVPLALFALNRQRLCERLRKNPAVQAGSIVVLQGGEETQRYCTD 60
Qy 61 TGVLFLQESFFHWAFGVTEPGCYGVIDVDTGKSTLFVPRLPASHATWMGKIHSKEHFKEK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TGVLFLQESFFHWAFGVTEPGCYGVIDVDTGKSTLFVPRLPASHATWMGKIHSKEHFKEK 120
Qy 121 YAVDDVQYVDEIASVLTSQKPSVLLTLRGVNTDSGSVCREASFDGISKFEVNNTILHPEI 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 YAVDDVQYVDEIASVLTSQKPSVLLTLRGVNTDSGSVCREASFDGISKFEVNNTILHPEI 180
Qy 181 VESRVFKTDMELEVLRYTNKISSEAHREVMKAVKVGMKEYGLESLFEHYCYSRGGMRHSS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VESRVFKTDMELEVLRYTNKISSEAHREVMKAVKVGMKEYGLESLFEHYCYSRGGMRHSS 240
Qy 241 YTCICGSGENSAVLHYGHAGAPNDRTIQNGDMCLFDMGGEYYSVASDITCSFPRNGKFTA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 YTCICGSGENSAVLHYGHAGAPNDRTIQNGDMCLFDMGGEYYSVASDITCSFPRNGKFTA 300
Qy 301 DQKAVYEAVLLSSRAVMGAMKPGDWWPDIDRLADRIHLEELAHMGILSGSVDAMVQAHLG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 DQKAVYEAVLLSSRAVMGAMKPGDWWPDIDRLADRIHLEELAHMGILSGSVDAMVQAHLG 360
Qy 361 AVFMPHGLGHFLGIDVHDVGGYPEGVERIDEPGLRSLRTARHLQPGMVLTVEPGIYFIDH 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 AVFMPHGLGHFLGIDVHDVGGYPEGVERIDEPGLRSLRTARHLQPGMVLTVEPGIYFIDH 420
Qy 421 LLDEALADPARASFLNREVLQRFRGFGGVRIEEDVVVIDSGIELLTCVPRTVEEIEACMA 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 LLDEALADPARASFLNREVLQRFRGFGGVRIEEDVVVIDSGIELLTCVPRTVEEIEACMA 480
Qy 481 GCDKAFTPFSGPK 493
|||||||||||||
Db 481 GCDKAFTPFSGPK 493
The ‘477 patent claims a method of using the same materials, a composition comprising G278 mutated PEPD of SEQ ID NO: 1 and further coagulation inhibitor, as instantly claimed invention.
The claims of ‘477 patent do not teach a pharmaceutically acceptable carrier, the identity agent fused to PEPD, or a container.
Golz, Copeland and Robison teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘477 claims, Golz, Copeland and Robison and make a pharmaceutical composition of the PEPD conjugated to a polyhistidine tag, IgG FC or a chemotherapeutic agent because Golz disclosed a pharmaceutical composition of PEPD fusion proteins (e.g. poly-histidine) and containers comprising PEPD and method of using PEPD for treatment of cancer, Copeland teaches a chemotherapeutic drug conjugated to a peptide used for treating cancer, and Robison teaches the Fc fusions are useful in therapy and diagnosis and in improved pharmacokinetic properties and can be used for the purpose of high-throughput screening assays. Thus, one skilled in the art would have been motivated to make a pharmaceutical composition comprising PEPD conjugated to a poly-histidine tag, IgG FC or a chemotherapeutic agent in order to increase the stability, for isolation/purification purposes, and/or to increase the therapeutic activity of the PEPD and place them in a container for storage, use or sale.
10. Claims 1-11 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11,103,563 (‘563).
Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of the claims are drawn to the same pharmaceutical composition comprising the same PEPD with the same mutation at position G278 and the same conjugate. The claims of the patent would anticipate the presently claimed invention.
The instant claims are set forth above.
The claims of Patent ‘563 are drawn to:
A pharmaceutical composition for used in prophylaxis and/or therapy of ErbB2-positive cancer comprising a peptidase C (PEPD) which comprises a mutation of G278D of SEQ ID NO:1 and has less dipeptide hydrolysis activity, wherein the composition further comprises a coagulation inhibitor and the PEPD is a fusion protein, wherein the PEPD is fused with polyhistidine tag or Fc region and chemotherapeutic agent.
Thus, the two sets of claims comprise the same a pharmaceutical composition comprising the same material comprising PEPD alone, or with a coagulation inhibitor, wherein the PEPD has a mutation at position G278, and PEPD is fused to polyhistidine tag or Fc region or chemotherapeutic agent. The only difference is the Patent ‘563 claims wherein the PEPD comprises SEQ ID NO:1 having a G278D change in said sequence, while the instant application merely claims mutation G278. Thus, the claims of the patent ‘563 recite a species of the presently claimed invention, therefore, would anticipate the present claimed invention.
It is noted that the instant application is a continuation application of '563 patent.
According to US patent law, obtaining more than one patents from one same or similar invention is prohibited. Terminal disclaimer must be filed to overcome the rejection.
11. Claims 1-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of co-pending Application No. 18/708,140 (published as US 2025/0009852 A1) in view of in view of Golz et al (WO 2004/104595, Dec 2, 2004, IDS). “Golz”, in view of US 2002/0103133 A1 (Copeland et al, Aug 2002, IDS), “Copeland”, in view of US Pat. No. 6,395,889 (Robison, KE, May 28, 2002), “Robison” and in view of Ledoux et al. (Am. J. Hum. Genet 59:1035-1039, 1996), “Ledoux”.
The ’140 claims are drawn to:
1. A method for inhibiting growth of cancer in an individual comprising administering to the individual an effective amount of a combination comprising peptidase D (PEPD), a sheddase inhibitor, and optionally a chemotherapeutic agent and a coagulation inhibitor.
2. The method of claim 1, wherein the method also comprises administering the chemotherapeutic agent and the coagulation inhibitor.
3. The method of claim 2, wherein the PEPD comprises a mutation of G at position 278 of SEQ ID NO:1 wherein the mutation is a change of glycine at position 278 to an amino acid other than aspartic acid.
The ‘140 claims do not teach a pharmaceutically acceptable carrier, PEPD fusion proteins , or a container.
Golz, Copeland, Robison and Ledoux teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘140 claims, Golz, Copeland and Robison and make a pharmaceutical composition of the PEPD the ‘140 claims conjugated to a polyhistidine tag, IgG FC or a chemotherapeutic agent because Golz disclosed a pharmaceutical composition of PEPD fusion proteins (e.g. poly-histidine) and containers comprising PEPD and method of using PEPD for treatment of cancer, Copeland teaches a chemotherapeutic drug conjugated to a peptide used for treating cancer, and Robison teaches the Fc fusions are useful in therapy and diagnosis and in improved pharmacokinetic properties and can be used for the purpose of high-throughput screening assays. Thus, one skilled in the art would have been motivated to make a pharmaceutical composition comprising PEPD conjugated to a poly-histidine tag, IgG FC or a chemotherapeutic agent in order to increase the stability, for isolation/purification purposes, and/or to increase the therapeutic activity of the PEPD and place them in a container for storage, use or sale.
Additionally, it would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high that mutations of glycine at position 278 would reduce the dipeptide hydrolysis activity of the PEPD because Ledoux teaches the the PEPD with a G278D mutation is enzymatically inactive. Thus, mutation of glycine at position 278 would reduce dipeptide hydrolysis activity as compared to SEQ ID NO: 1.
This is a provisional nonstatutory double patenting rejection.
12. Claims 1-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of co-pending Application No. 19/102,539 (published as US 2026/0055208 A1) in view of in view of Golz et al (WO 2004/104595, Dec 2, 2004, IDS). “Golz”, in view of US 2002/0103133 A1 (Copeland et al, Aug 2002, IDS), “Copeland”, and in view of US Pat. No. 6,395,889 (Robison, KE, May 28, 2002), “Robison”.
The ’539 claims are drawn to:
1. A method for therapy of cancer comprising administering to an individual in need thereof an antibody or antigen binding fragment thereof that specifically binds to Factor XII, and peptidase D (PEPD).
2. The method of claim 1, wherein the antibody that specifically binds to Factor XII is garadacimab.
3. The method of claim 2, wherein the PEPD has less dipeptide hydrolysis activity as compared to a PEPD comprising the sequence of SEQ ID NO:1.
4. The method of claim 3, wherein the PEPD comprises a mutation of glycine at position 278 of SEQ ID NO:1.
5. The method of claim 3, wherein the mutation glycine at position 278 of SEQ ID NO: 1 comprises aspartic acid at position 278 of SEQ ID NO:1.
6. The method of claim 5, wherein the cancer is ErbB1 or ErbB2 positive cancer.
Garadacimab blocks Factor XIIa in the coagulation cascade (see Fig 1 of US 2026/0055208), thus it is a coagulation inhibitor.
The ‘539 claims do not teach a pharmaceutically acceptable carrier, PEPD fusion proteins, or a container.
Golz, Copeland, Robison and Ledoux teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘539 claims, Golz, Copeland and Robison and make a pharmaceutical composition of the PEPD the ‘539 claims conjugated to a polyhistidine tag, IgG FC or a chemotherapeutic agent because Golz disclosed a pharmaceutical composition of PEPD fusion proteins (e.g. poly-histidine) and containers comprising PEPD and method of using PEPD for treatment of cancer, Copeland teaches a chemotherapeutic drug conjugated to a peptide used for treating cancer, and Robison teaches the Fc fusions are useful in therapy and diagnosis and in improved pharmacokinetic properties and can be used for the purpose of high-throughput screening assays. Thus, one skilled in the art would have been motivated to make a pharmaceutical composition comprising PEPD conjugated to a poly-histidine tag, IgG Fc or a chemotherapeutic agent in order to increase the stability, for isolation/purification purposes, and/or to increase the therapeutic activity of the PEPD and place them in a container for storage, use or sale.
This is a provisional nonstatutory double patenting rejection.
Conclusion
13. No claims allowed.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached M-F 8:30-5:30 Eastern Time.
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/PETER J REDDIG/ Primary Examiner, Art Unit 1646
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